sa1671sa1691</head><body><p>KNG1 forms complex with KLKB1. PMID: 7944388 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re6"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:7944388" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa13"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa177" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa13_in_0" /><qual:input qual:qualitativeSpecies="sa175" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa13_in_1" /><qual:input qual:qualitativeSpecies="sa202" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_csa13_in_2" /><qual:input qual:qualitativeSpecies="sa200" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa13_in_3" /><qual:input qual:qualitativeSpecies="csa25" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_csa13_in_4" /><qual:input qual:qualitativeSpecies="sa205" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_csa13_in_5" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa13" qual:transitionEffect="assignmentLevel" qual:id="tr_csa13_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa177</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa175</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa202</ci><cn type="integer">0</cn></apply></apply><apply><and /><apply><eq /><ci>sa200</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa25</ci><cn type="integer">0</cn></apply><apply><eq /><ci>sa205</ci><cn type="integer">0</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>F5a interacts with F10a. PMID:2303476 </p> <p>Factor F9a increases hydrolysis of F10. PMID:11551226 AT-III inhibits thrombin,factors IXa, Xa and XIa. PMID:15853774 </p> <p>Human Factor V was activated by Factor X and Thrombin. PMID: 2322551 Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation.PMID: 6282863 PROC inhibits activation of coagulation factor F5a. PMID:6572921 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re193"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2303476" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re173"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:11551226" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15853774" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#r129"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6282863" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6572921" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2322551" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa12"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa175" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa12_in_0" /><qual:input qual:qualitativeSpecies="sa180" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa12_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa12" qual:transitionEffect="assignmentLevel" qual:id="tr_csa12_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa175</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa180</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Heme binds to factor VIII and inhibits its interaction with activated factor IX. PMID:22471307 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re191"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22471307" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa16"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa224" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa16_in_0" /><qual:input qual:qualitativeSpecies="sa225" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa16_in_1" /><qual:input qual:qualitativeSpecies="sa499" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa16_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa16" qual:transitionEffect="assignmentLevel" qual:id="tr_csa16_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa224</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa225</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa499</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>SERPINE1 forms complex with PLAT. PMID:22449964 The level of t-PA/PAI-1 Complex (t-PAIC) was higher in COVID-19 patients were higher than health controls, and also higher in the patients with thrombotic disease than without thrombotic disease in whole blood samples. DOI:10.1101/2020.04.25.20077842 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re182"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22449964" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:doi:10.1101%2F2020.04.25.20077842" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa17"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa499" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa17_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa17" qual:transitionEffect="assignmentLevel" qual:id="tr_csa17_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa499</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. PMID:2117226 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re192"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32172226" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa14"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa202" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa14_in_0" /><qual:input qual:qualitativeSpecies="sa181" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa14_in_1" /><qual:input qual:qualitativeSpecies="sa481" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa14_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa14" qual:transitionEffect="assignmentLevel" qual:id="tr_csa14_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa202</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa181</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa481</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Antithrombin interacts with thrombin. PMID:8136018 The level of TAT Complex was higher in COVID-19 patients were higher than health controls, and also higher in the patients with thrombotic disease than without thrombotic disease in whole blood samples. DOI:10.1101/2020.04.25.20077842 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re179"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8136018" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:doi:10.1101%2F2020.04.25.20077842" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa25"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa181" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa25_in_0" /><qual:input qual:qualitativeSpecies="sa301" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa25_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa25" qual:transitionEffect="assignmentLevel" qual:id="tr_csa25_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa181</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa301</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Thrombomodulin binds to thrombin at an anion-binding exosite on the carboxyl-terminal side of the substrate binding cleft. This interaction interferes with the recognition and cleavage of fibrinogen, factor V, and the platelet thrombin receptor. PMID: 8388351 Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and Factor V activation. PMID: 6282863 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re256"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6282863" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8388351" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa27"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa310" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa27_in_0" /><qual:input qual:qualitativeSpecies="csa26" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa27_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa27" qual:transitionEffect="assignmentLevel" qual:id="tr_csa27_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa310</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa26</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C3-activation by the classical, lectin or alternative C3 convertase results in the formation of the C5 (C3bBbC3b) convertase. PMID: 26521297 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re285"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26521297" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa32"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa32_in_0" /><qual:input qual:qualitativeSpecies="sa314" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa32_in_1" /><qual:input qual:qualitativeSpecies="csa35" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa32_in_2" /><qual:input qual:qualitativeSpecies="csa27" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa32_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa32" qual:transitionEffect="assignmentLevel" qual:id="tr_csa32_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply><apply><and /><apply><or /><apply><eq /><ci>csa35</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa27</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa314</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The elevated circulatory levels of C5b-9 were also reported in severe cases of COVID-19. PMCID:PMC7260598 </p> <p>Molar ratio estimates indicated that 1 mol of C5b,C9dimer,C6,C7,an dC8 and 3-4mol of C9 monomer were present per M C5b-9 complex. PMID: 6796960 The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. C6 binds the labile C5b intermediate, resulting in a stable C5b6 complex. C7 binds C5b6, anchoring the newly formed C5b7 complex to the membrane surface. C8, a heterotrimeric protein composed of C8α, C8β and C8γ, is incorporated into the assembly precursor forming C5b8 and marking the first membrane penetrating event. Finally, multiple copies of C9 join the assembly and span membrane, resulting in the final membrane attack complex (MAC). PMID: 28630159 </p> <p>Stable complexes of phospholipid and protein were formed by C5b--7, C5b--8, C5b--9, and the MAC (C5b--9 dimer) and they exhibited densities of 1.2164, 1.184, 1.2055, and 1.2275 g/ml, respectively. PMID: 284414 The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. C6 binds the labile C5b intermediate, resulting in a stable C5b6 complex. C7 binds C5b6, anchoring the newly formed C5b7 complex to the membrane surface. C8, a heterotrimeric protein composed of C8α, C8β and C8γ, is incorporated into the assembly precursor forming C5b8 and marking the first membrane penetrating event. Finally, multiple copies of C9 join the assembly and span membrane, resulting in the final membrane attack complex (MAC). PMID: 28630159 </p> <p>Nascent C5b combines with C6 and C7,resulting in the formation of a C5b67 trimolecular complex. PMID: 5058233 The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. C6 binds the labile C5b intermediate, resulting in a stable C5b6 complex. C7 binds C5b6, anchoring the newly formed C5b7 complex to the membrane surface. C8, a heterotrimeric protein composed of C8α, C8β and C8γ, is incorporated into the assembly precursor forming C5b8 and marking the first membrane penetrating event. Finally, multiple copies of C9 join the assembly and span membrane, resulting in the final membrane attack complex (MAC). PMID: 28630159 </p> <p>Nascent C5b combines with C6 and C7,resulting in the formation of a C5b67 trimolecular complex. PMID: 5058233 The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. C6 binds the labile C5b intermediate, resulting in a stable C5b6 complex. C7 binds C5b6, anchoring the newly formed C5b7 complex to the membrane surface. C8, a heterotrimeric protein composed of C8α, C8β and C8γ, is incorporated into the assembly precursor forming C5b8 and marking the first membrane penetrating event. Finally, multiple copies of C9 join the assembly and span membrane, resulting in the final membrane attack complex (MAC). PMID: 28630159 </p> <p>The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. PMID: 30083158 Kinetic parameters revealed that the soluble form of the enzyme (C4b,C2a) cleaved C5 at a catalytic rate similar to that of the surface-bound form (EAC1,C4b,C2a). PMID: 12878586 When the density of C3b molecules on the cell surface becomes sufficiently high, the existing C3 convertases (C4b2a and C3bBb) gain the ability to cleave C5, leading to formation of C5a and C5b. PMID: 30083158 The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. C6 binds the labile C5b intermediate, resulting in a stable C5b6 complex. C7 binds C5b6, anchoring the newly formed C5b7 complex to the membrane surface. C8, a heterotrimeric protein composed of C8α, C8β and C8γ, is incorporated into the assembly precursor forming C5b8 and marking the first membrane penetrating event. Finally, multiple copies of C9 join the assembly and span membrane, resulting in the final membrane attack complex (MAC). PMID: 28630159 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re324"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pmc:PMC7260598" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re267"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6796960" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re266"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:284414" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re264"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:5058233" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re263"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:5058233" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re262"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30083158" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:12878586" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa35"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa365" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa35_in_0" /><qual:input qual:qualitativeSpecies="sa367" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa35_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa35" qual:transitionEffect="assignmentLevel" qual:id="tr_csa35_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa365</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa367</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The classical pathway is activated by antibodies [one IgM molecule, multiple (preferably 6) IgG molecules] leading to the formation of the classical C3 convertase (C2aC4b) by the activation C2 and C4 by C1s/C1r. PMID: 26521297 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re278"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26521297" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:brenda:3.4.21.43" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa37"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa398" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa37_in_0" /><qual:input qual:qualitativeSpecies="sa391" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa37_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa37" qual:transitionEffect="assignmentLevel" qual:id="tr_csa37_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa398</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa391</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2) was presented, which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. PMID:32275855 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re305"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32275855" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:2697049" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa38"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa212" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa38_in_0" /><qual:input qual:qualitativeSpecies="sa412" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa38_in_1" /><qual:input qual:qualitativeSpecies="sa481" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa38_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa38" qual:transitionEffect="assignmentLevel" qual:id="tr_csa38_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa212</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa412</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa481</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Human alpha 2-antiplasmin rapidly forms a stable, equimolar complex with either its target enzyme, plasmin, or with trypsin. PMID: 2437112 The level of SERPINF2-Plasmin Complex (PIC) was higher in COVID-19 patients were higher than health controls, and also higher in the patients with thrombotic disease than without thrombotic disease in whole blood. DOI:10.1101/2020.04.25.20077842 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re326"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2437112" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:doi:10.1101%2F2020.04.25.20077842" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa42"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa17" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa42_in_0" /><qual:input qual:qualitativeSpecies="sa431" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa42_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa42" qual:transitionEffect="assignmentLevel" qual:id="tr_csa42_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>csa17</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa431</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Human glycoprotein VI binds to immobilized fibrinogen and show that this contributes to platelet spreading and platelet aggregation under flow. PMID: 29472360 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re363"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29472360" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa40"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa39" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa40_in_0" /><qual:input qual:qualitativeSpecies="sa411" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa40_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa40" qual:transitionEffect="assignmentLevel" qual:id="tr_csa40_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>csa39</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa411</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>GPVI and α2β1 to primary hemostasis confirm that collagen binding by VWF, GPVI, and α2β1 have major roles in thrombus formation. PMID: 25051961 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re358"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25051961" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa39"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa431" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa39_in_0" /><qual:input qual:qualitativeSpecies="csa41" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa39_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa39" qual:transitionEffect="assignmentLevel" qual:id="tr_csa39_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa431</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa41</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>GPVI and α2β1 to primary hemostasis confirm that collagen binding by VWF, GPVI, and α2β1 have major roles in thrombus formation. PMID: 25051961 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re357"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25051961" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa43"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa32" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa43_in_0" /><qual:input qual:qualitativeSpecies="sa391" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa43_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa43" qual:transitionEffect="assignmentLevel" qual:id="tr_csa43_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>csa32</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa391</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>There was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined. PMID: 32299776 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re309"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32299776" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa165"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa170" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa165_in_0" /><qual:input qual:qualitativeSpecies="sa167" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa165_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa165" qual:transitionEffect="assignmentLevel" qual:id="tr_sa165_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa170</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa167</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p> Accelerated cleavage of surface-bound radiolabeled HF (Factor XII) was demonstrated after incubation with HFa (FXIIa) but not HFf, indicating that HFa (FXIIa) is the form of active enzyme responsible for autocleavage. PMID: 7391081 The effective contact activation of Hageman factor in plasma requires prekallikrein and HMWK, and that plasmas deficient in either of these proteins do not develop normal clotting, kinin, and fibrinolytic activities upon exposure to glass. PMID: 864009 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re8"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:7391081" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:864009" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa171"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa170" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa171_in_0" /><qual:input qual:qualitativeSpecies="sa167" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa171_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa171" qual:transitionEffect="assignmentLevel" qual:id="tr_sa171_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa170</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa167</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p> Accelerated cleavage of surface-bound radiolabeled HF (Factor XII) was demonstrated after incubation with HFa (FXIIa) but not HFf, indicating that HFa (FXIIa) is the form of active enzyme responsible for autocleavage. PMID: 7391081 The effective contact activation of Hageman factor in plasma requires prekallikrein and HMWK, and that plasmas deficient in either of these proteins do not develop normal clotting, kinin, and fibrinolytic activities upon exposure to glass. PMID: 864009 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re8"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:7391081" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:864009" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa172"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa165" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa172_in_0" /><qual:input qual:qualitativeSpecies="sa181" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa172_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa172" qual:transitionEffect="assignmentLevel" qual:id="tr_sa172_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa165</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa181</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. PMID:21304106 F2(Thrombin) increases activation of coagulation factor F11. PMID:8631976 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re9"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21304106" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8631976" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa173"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa165" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa173_in_0" /><qual:input qual:qualitativeSpecies="sa181" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa173_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa173" qual:transitionEffect="assignmentLevel" qual:id="tr_sa173_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa165</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa181</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. PMID:21304106 F2(Thrombin) increases activation of coagulation factor F11. PMID:8631976 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re9"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21304106" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8631976" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa175"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa174" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa175_in_0" /><qual:input qual:qualitativeSpecies="sa173" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa175_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa175" qual:transitionEffect="assignmentLevel" qual:id="tr_sa175_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa174</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa173</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Factor IX Activation by Factor XIa proceeds without release of a free intermediate. PMID:9100000 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re157"> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:9100000" /> </rdf:Bag> </bqmodel:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa178"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa177" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa178_in_0" /><qual:input qual:qualitativeSpecies="sa175" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa178_in_1" /><qual:input qual:qualitativeSpecies="sa202" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa178_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa178" qual:transitionEffect="assignmentLevel" qual:id="tr_sa178_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa177</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa175</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa202</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Factor F9a increases hydrolysis of F10. PMID:11551226 AT-III inhibits thrombin,factors IXa, Xa and XIa. PMID:15853774 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re173"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:11551226" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15853774" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa179"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa179_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa179" qual:transitionEffect="assignmentLevel" qual:id="tr_sa179_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased in patients with COVID-19. PMID: 32367170 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re295"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32367170" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa180"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa179" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa180_in_0" /><qual:input qual:qualitativeSpecies="sa181" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa180_in_1" /><qual:input qual:qualitativeSpecies="sa205" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa180_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa180" qual:transitionEffect="assignmentLevel" qual:id="tr_sa180_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa179</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa181</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa205</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Thrombin catalyzes the proteolytic activation of factor VIII, cleaving two sites in the heavy chain and one site in the light chain of the procofactor. PMID:15746105 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re390"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15746105" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa181"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa203" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa181_in_0" /><qual:input qual:qualitativeSpecies="sa202" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa181_in_1" /><qual:input qual:qualitativeSpecies="sa355" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa181_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa181" qual:transitionEffect="assignmentLevel" qual:id="tr_sa181_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa203</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa355</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa202</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The inhibitory capacity of antithrombin III (AT III) was measured by a quantitative method independent of the velocity of inhibition. When AT III was in excess of thrombin in plasma or in purified system the capacity of inhibitor decreased quantitatively in proportion to the amount of thrombin neutralized. Heparin present in reaction together with thrombin invariably induced a more extensive utilization of inhibitor than thrombin alone. PMID: 579490 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re196"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:579490" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa183"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa179" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa183_in_0" /><qual:input qual:qualitativeSpecies="sa181" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa183_in_1" /><qual:input qual:qualitativeSpecies="sa205" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa183_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa183" qual:transitionEffect="assignmentLevel" qual:id="tr_sa183_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa179</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa181</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa205</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Thrombin catalyzes the proteolytic activation of factor VIII, cleaving two sites in the heavy chain and one site in the light chain of the procofactor. PMID:15746105 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re390"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15746105" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa194"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa480" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa194_in_0" /><qual:input qual:qualitativeSpecies="sa195" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa194_in_1" /><qual:input qual:qualitativeSpecies="sa198" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa194_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa194" qual:transitionEffect="assignmentLevel" qual:id="tr_sa194_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa480</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa195</ci><cn type="integer">1</cn></apply><apply><and /><apply><eq /><ci>sa195</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa198</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>SARS-COV-2 infection icreases the level of Angiotesin II in blood plasma. PMID:32048163 </p> <p>SARS-COV-2 infection icreases the level of Angiotesin II in blood plasma. PMID: 32048163 </p> <p>In a classical view, the renin–angiotensin system (RAS) is considered an endocrine system whose active metabolite, the angiotensin II (Ang II), is produced by enzymatic sequential cleavage from the angiotensinogen substratum of hepatic origin. In the bloodstream, the renin, a highly specifi c protease, converts the circulating angiotensinogen into the decapeptide Ang I, which, in turn is converted to Ang II by the angiotensin-converting enzyme (ACE) action. This enzyme also inactivates bradykinin (BK) and is highly found in the endothelial cells membranes of the pulmonary circulation. PMID:19065996 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re375"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32048163" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re183"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32048163" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:2697049" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re132"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:190881" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10969042" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa195"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa196" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa195_in_0" /><qual:input qual:qualitativeSpecies="sa197" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa195_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa195" qual:transitionEffect="assignmentLevel" qual:id="tr_sa195_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa196</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa197</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p> Renin provides only one known function, to cleave the 10-amino acid precursor peptide angiotensin I (Ang-I),1 from the N terminus of mature angiotensinogen (AGT). PMID:10585461 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re14"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10585461" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30934934" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6172448" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa197"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa415" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa197_in_0" /><qual:input qual:qualitativeSpecies="sa251" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa197_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa197" qual:transitionEffect="assignmentLevel" qual:id="tr_sa197_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa415</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa251</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Human urinary kallikrein converts inactive to active renin. PMID: 692685 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re330"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:692685" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa198"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa503" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa198_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa198" qual:transitionEffect="assignmentLevel" qual:id="tr_sa198_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa503</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Aldosterone significantly increased steady-state ACE mRNA levels and its enzymatic activities via a JAK2-dependent pathway in rat endothelial cells. PMID:15932931 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re391"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:5932931" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa202"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa499" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa202_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa202" qual:transitionEffect="assignmentLevel" qual:id="tr_sa202_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa499</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p> Whole blood from 24 patients admitted at the intensive care unit because of Covid-19 was collected and evaluated. Fibrinogen was increased and D-dimer was dramatically increased. C-reactive protein was increased. Factor VIII and von Willebrand factor (n=11) were increased. Antithrombin (n=11) was marginally decreased and protein C (n=11) was increased. The results of this cohort of patients with Covid-19 are not consistent with acute disseminated intravascular coagulation (DIC), rather they support hypercoagulability together with a severe inflammatory state. PMID: 32302438 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re296"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32302438" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa203"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa182" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa203_in_0" /><qual:input qual:qualitativeSpecies="csa13" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa203_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa203" qual:transitionEffect="assignmentLevel" qual:id="tr_sa203_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa182</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa13</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Conversion of prothrombin to thrombin catalyzes by F5a-F10a complex. PMID:4430674,PMID:3818642 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re195"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:4430674" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:3818642" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa205"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa205_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa205" qual:transitionEffect="assignmentLevel" qual:id="tr_sa205_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Fibrinogen was increased and D-dimer was dramatically increased. C-reactive protein was increased in covid-19 patients. Factor VIII and von Willebrand factor (n=11) were increased. Antithrombin (n=11) was marginally decreased and protein C (n=11) was increased. PMID: 32302438 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re323"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32302438" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa210"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa424" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa210_in_0" /><qual:input qual:qualitativeSpecies="sa212" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa210_in_1" /><qual:input qual:qualitativeSpecies="sa227" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa210_in_2" /><qual:input qual:qualitativeSpecies="sa499" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa210_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa210" qual:transitionEffect="assignmentLevel" qual:id="tr_sa210_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>sa212</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa227</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa499</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa424</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>D-dimer is generated when the cross-linked fibrinnet work undergoes plasmin-mediated degradation. PMID: 29096812 CBP2 peptidase removes C-terminal lysine residues from fibrin that has already been partially degraded by plasmin. PMID:10574983 The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. PMID:32172226 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re346"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29096812" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10574983" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32172226" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa211"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa32" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa211_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa211" qual:transitionEffect="assignmentLevel" qual:id="tr_sa211_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>csa32</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Complement C5b-9 increases plasminogen binding and activation on human endothelial cells. PMID: 9012652 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re341"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:9012652" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa212"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa211" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa212_in_0" /><qual:input qual:qualitativeSpecies="sa213" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa212_in_1" /><qual:input qual:qualitativeSpecies="sa236" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa212_in_2" /><qual:input qual:qualitativeSpecies="sa173" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa212_in_3" /><qual:input qual:qualitativeSpecies="sa167" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa212_in_4" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa212" qual:transitionEffect="assignmentLevel" qual:id="tr_sa212_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>sa213</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa236</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa173</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa167</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa211</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>XIa can directly activate PG to PL. PMID:89876 Kallikrein activates PG to PL. PMID:3850647 tPA (PLAT) catalysis plasmin formation from plasminogen. PMID:2966802 Urokinase-type plasminogen activater catalyses plasmin formation from plasminogen. PMID:6539333 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re203"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:89876" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:3850647" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2966802" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6539333" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa213"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa402" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa213_in_0" /><qual:input qual:qualitativeSpecies="sa225" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa213_in_1" /><qual:input qual:qualitativeSpecies="sa224" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa213_in_2" /><qual:input qual:qualitativeSpecies="sa194" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa213_in_3" /><qual:input qual:qualitativeSpecies="sa400" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa213_in_4" /><qual:input qual:qualitativeSpecies="sa205" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa213_in_5" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa213" qual:transitionEffect="assignmentLevel" qual:id="tr_sa213_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa402</ci><cn type="integer">1</cn></apply><apply><and /><apply><or /><apply><eq /><ci>sa402</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa194</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa225</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa224</ci><cn type="integer">0</cn></apply><apply><eq /><ci>sa400</ci><cn type="integer">0</cn></apply><apply><eq /><ci>sa205</ci><cn type="integer">0</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>In vivo data suggest that infusion of bradykinin results in an increase in circulating t-PA levels without an effect on PAI-1. PMID: 9066005 </p> <p>Bradykinin stimulates tissue plasminogen activator release in human vasculature. PMID:10373228 Plasminogen activator inhibitor-1 is the Primary inhibitor of tissue-type plasminogen activator in pregnancy plasma. PMID:3124286 Ang II increased PAI-1 and tissue plasminogen activator (t-PA) release, while its metabolite angiotensin-(1-7) (Ang-(1-7)) amino acid fragment decreased them. PMID:12091055 Bovine-activated protein C also decreased PAI activity of whole blood and of serum. In contrast to the bovine molecule, human-activated protein C was much less profibrinolytic in these clot lysis assay systems and much less potent in causing the neutralization of PAI. This species specificity of activated protein C in clot lysis assays reflect the known in vivo profibrinolytic species specificity. a major mechanism for bovine protein C-dependent fibrinolysis in in vitro clot lysis assays involves a direct neutralization of PAI by activated protein C. PMID:3096399 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re372"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:9066005" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re180"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10373228" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:3124286" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:12091055" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:3096399" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa224"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa503" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa224_in_0" /><qual:input qual:qualitativeSpecies="sa194" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa224_in_1" /><qual:input qual:qualitativeSpecies="sa400" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa224_in_2" /><qual:input qual:qualitativeSpecies="sa242" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa224_in_3" /><qual:input qual:qualitativeSpecies="sa519" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa224_in_4" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa224" qual:transitionEffect="assignmentLevel" qual:id="tr_sa224_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>sa503</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa194</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa242</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa519</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa400</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Ang II increased PAI-1 and tissue plasminogen activator (t-PA) release, while its metabolite angiotensin-(1-7) (Ang-(1-7)) amino acid fragment decreased them. PMID:12091055 Although IL-6 alone had only a modest effect on PAI-1 expression, in combination with IL-1, it caused a synergistic induction of PAI-1 mRNA accumulation. PMID:8034668 Aldosterone increases expression of PAI-1 in H9c2 cells expressed NR3C2. PMID:20591974 Ang II activates PAI-1 gene expression through the AT1 receptor and involves the calcium-dependent activation of calcineurin and the nuclear translocation of NFAT. PMID:11983698 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re377"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2091055" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8034668" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:20591974" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqmodel:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:11983698" /> </rdf:Bag> </bqmodel:is> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa227"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa181" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa227_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa227" qual:transitionEffect="assignmentLevel" qual:id="tr_sa227_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa181</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>TAFI(CPB2 gene) peptidase was activated by thrombin. PMID: 7782309 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re181"> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23809134" /> </rdf:Bag> </bqmodel:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9823" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa236"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa224" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa236_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa236" qual:transitionEffect="assignmentLevel" qual:id="tr_sa236_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa224</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>PAI-1 specifically and rapidly inhibits uPA and tissue-type PA (tPA). PMID:21199867 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re268"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21199867" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa238"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa238_in_0" /><qual:input qual:qualitativeSpecies="sa416" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa238_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa238" qual:transitionEffect="assignmentLevel" qual:id="tr_sa238_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa416</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>IL-6 (19.23%), IL-10 (50%), TNF-alpha (11.54%) and IFN-gamma (19.23%) were elevated 6 infants with SARS-CoV-2 infection in Wuhan. PMID:32504360 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re344"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32504360" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa242"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa242_in_0" /><qual:input qual:qualitativeSpecies="sa416" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa242_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa242" qual:transitionEffect="assignmentLevel" qual:id="tr_sa242_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa416</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>A meta-analysis on COVID-19 patients was performed, comparing 21 studies, totaling 3377 patients and 33 laboratory parameters. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Inflammatory biomarkers such as IL-6, IL-10 and serum ferritin were highly upregulated in patients with severe and fatal disease. PMID:32286245 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re333"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32286245" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa244"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa244_in_0" /><qual:input qual:qualitativeSpecies="sa416" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa244_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa244" qual:transitionEffect="assignmentLevel" qual:id="tr_sa244_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa416</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>the expression of IL1-beta was increased in blood od COVID-19 patient. PMID: 32359396 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re332"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32359396" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa250"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa11" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa250_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa250" qual:transitionEffect="assignmentLevel" qual:id="tr_sa250_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>csa11</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Factor XIIa converts prekallikrein to kallikrein. PMID: 6768384 Kallikrein digests KNG1 to release bradykinin. PMID: 4627469 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#CDMT00119"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6768384" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:4627469" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa251"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa167" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa251_in_0" /><qual:input qual:qualitativeSpecies="sa165" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa251_in_1" /><qual:input qual:qualitativeSpecies="csa11" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa251_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa251" qual:transitionEffect="assignmentLevel" qual:id="tr_sa251_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa167</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa165</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>csa11</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. PMID:21304106 </p> <p>Factor XIIa converts prekallikrein to kallikrein. PMID: 6768384 Kallikrein digests KNG1 to release bradykinin. PMID: 4627469 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re329"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21304106" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#CDMT00119"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6768384" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:4627469" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa253"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa468" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa253_in_0" /><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa253_in_1" /><qual:input qual:qualitativeSpecies="sa314" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa253_in_2" /><qual:input qual:qualitativeSpecies="csa35" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa253_in_3" /><qual:input qual:qualitativeSpecies="csa27" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa253_in_4" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa253" qual:transitionEffect="assignmentLevel" qual:id="tr_sa253_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa468</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply><apply><and /><apply><or /><apply><eq /><ci>csa35</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa27</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa314</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>In an arterial thrombosis model, plasminogen activator administration increased C5a levels. PMID: 27077125 </p> <p>The elevated circulatory levels of C5a were also reported in severe cases of COVID-19. PMCID:PMC7260598 </p> <p>The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. PMID: 30083158 Kinetic parameters revealed that the soluble form of the enzyme (C4b,C2a) cleaved C5 at a catalytic rate similar to that of the surface-bound form (EAC1,C4b,C2a). PMID: 12878586 When the density of C3b molecules on the cell surface becomes sufficiently high, the existing C3 convertases (C4b2a and C3bBb) gain the ability to cleave C5, leading to formation of C5a and C5b. PMID: 30083158 The first step requires cleavage of C5 into the small anaphylatoxin C5a and the large fragment C5b by the C5 convertase. C6 binds the labile C5b intermediate, resulting in a stable C5b6 complex. C7 binds C5b6, anchoring the newly formed C5b7 complex to the membrane surface. C8, a heterotrimeric protein composed of C8α, C8β and C8γ, is incorporated into the assembly precursor forming C5b8 and marking the first membrane penetrating event. Finally, multiple copies of C9 join the assembly and span membrane, resulting in the final membrane attack complex (MAC). PMID: 28630159 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re343"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27077125" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re334"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pmc:PMC7260598" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re262"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30083158" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:12878586" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa271"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa194" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_0" /><qual:input qual:qualitativeSpecies="csa32" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_1" /><qual:input qual:qualitativeSpecies="sa387" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_2" /><qual:input qual:qualitativeSpecies="sa411" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_3" /><qual:input qual:qualitativeSpecies="sa410" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_4" /><qual:input qual:qualitativeSpecies="sa306" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_5" /><qual:input qual:qualitativeSpecies="sa304" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_6" /><qual:input qual:qualitativeSpecies="sa238" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_7" /><qual:input qual:qualitativeSpecies="sa242" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_8" /><qual:input qual:qualitativeSpecies="sa244" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa271_in_9" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa271" qual:transitionEffect="assignmentLevel" qual:id="tr_sa271_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa194</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa32</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa387</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa411</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa410</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa306</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa304</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa238</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa242</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa244</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Angiotensin II induced hypertension is accompanied by enhanced microvascular thrombosis in arterioles. PMID:20975035 </p> <p>C5b-9 deposits were present in 78.6% of thrombotic microangiopathy cases and in 39.6% of controls (n=53), but the staining pattern differed between cases and controls. PMID: 25573909 </p> <p>Deposits of C4d, mannose-binding lectin, C1q, IgM, and C5b-9 were scored in the glomeruli, peritubular capillaries, and arterioles. Notably, C4d deposits were present in 88.1% of TMA cases, and the various clinical conditions had distinct staining patterns within the various compartments of the renal vasculature. Classical pathway activation was observed in 90.5% of TMA cases. Complement activation has a major role in thrombotic microangiopathy (TMA), a disorder that can occur in a variety of clinical conditions. PMID: 25573909 </p> <p>VWF-mediated process is involved in platelet aggregation in stenotic arteries leading to acute thrombotic occlusion. PMID: 3500650 </p> <p>Plasma concentration of C-reactive protein was correlated with a risk of developing peripheral vascular disease. PMID: 9490235 </p> <p>Patients who had thrombotic events displayed higher monocyte CD25 (IL2RA) levels (6.2%) than those without symptoms (1.3%) and controls (2.6%), p=0.0006. PMID:20483636 </p> <p>The effects of IL-1β, IL-6 and IL-8 at low physiological levels, representative of chronic inflammation, by using scanning electron microscopy and thromboelastography were investigated. All three interleukins caused the viscoelastic properties to display an increased hypercoagulability of whole blood and pathology of both erythrocytes and platelets. The most pronounced changes were noted where all three cytokines caused platelet hyper-activation and spreading. PMID: 27561337 </p> <p>TNFα accelerates thrombus formation in an in vivo model of arteriolar thrombosis. PMID: 23079185 </p> <p>The effects of IL-1β, IL-6 and IL-8 at low physiological levels, representative of chronic inflammation, by using scanning electron microscopy and thromboelastography were investigated. All three interleukins caused the viscoelastic properties to display an increased hypercoagulability of whole blood and pathology of both erythrocytes and platelets. The most pronounced changes were noted where all three cytokines caused platelet hyper-activation and spreading. PMID: 27561337 </p> <p>The effects of IL-1β, IL-6 and IL-8 at low physiological levels, representative of chronic inflammation, by using scanning electron microscopy and thromboelastography were investigated. All three interleukins caused the viscoelastic properties to display an increased hypercoagulability of whole blood and pathology of both erythrocytes and platelets. The most pronounced changes were noted where all three cytokines caused platelet hyper-activation and spreading. PMID: 27561337 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re371"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:20975035" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re342"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25573909" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re340"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25573909" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re321"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:3500650" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re320"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:9490235" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re260"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:20483636" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re259"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27561337" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re231"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27561337" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re229"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27561337" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re227"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27561337" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa301"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa499" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa301_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa301" qual:transitionEffect="assignmentLevel" qual:id="tr_sa301_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa499</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The level of Thrombomodulin was higher in COVID-19 patients were higher than health controls, and also higher in the patients with thrombotic disease than without thrombotic disease in whole blood samples. DOI:10.1101/2020.04.25.20077842 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re328"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:doi:10.1101%2F2020.04.25.20077842" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa304"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa304_in_0" /><qual:input qual:qualitativeSpecies="sa416" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa304_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa304" qual:transitionEffect="assignmentLevel" qual:id="tr_sa304_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa416</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>A meta-analysis on COVID-19 patients was performed, comparing 21 studies, totaling 3377 patients and 33 laboratory parameters. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Inflammatory biomarkers such as IL-8, IL2R, IL-1B, IL-6, IL-10 and serum ferritin were highly upregulated in patients with severe and fatal disease. PMID:32286245 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re336"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32286245" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa306"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa306_in_0" /><qual:input qual:qualitativeSpecies="sa416" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa306_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa306" qual:transitionEffect="assignmentLevel" qual:id="tr_sa306_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa416</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>A meta-analysis on COVID-19 patients was performed, comparing 21 studies, totaling 3377 patients and 33 laboratory parameters. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Inflammatory biomarkers such as IL-8, IL2R, IL-1B, IL-6, IL-10 and serum ferritin were highly upregulated in patients with severe and fatal disease. PMID:32286245 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re337"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32286245" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa308"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa252" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa308_in_0" /><qual:input qual:qualitativeSpecies="csa26" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa308_in_1" /><qual:input qual:qualitativeSpecies="csa35" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa308_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa308" qual:transitionEffect="assignmentLevel" qual:id="tr_sa308_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>csa26</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa35</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa252</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C3 converting enzyme activity digests C3 into C3a and C3b fragments. PMID; 1244096 C3 convertases, C4b2a and C3bBb, cleave C3 into the anaphylatoxin C3a and C3b. PMID: 17395591 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re261"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:427127" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17395591" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa310"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa252" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa310_in_0" /><qual:input qual:qualitativeSpecies="csa26" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa310_in_1" /><qual:input qual:qualitativeSpecies="csa35" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa310_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa310" qual:transitionEffect="assignmentLevel" qual:id="tr_sa310_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>csa26</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa35</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa252</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C3 converting enzyme activity digests C3 into C3a and C3b fragments. PMID; 1244096 C3 convertases, C4b2a and C3bBb, cleave C3 into the anaphylatoxin C3a and C3b. PMID: 17395591 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re261"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:427127" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17395591" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa358"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa362" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa358_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa358" qual:transitionEffect="assignmentLevel" qual:id="tr_sa358_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa362</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>MBL2 interacts with MASP1. PMID:11290788 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re275"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:11290788" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa364"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa363" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa364_in_0" /><qual:input qual:qualitativeSpecies="sa459" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa364_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa364" qual:transitionEffect="assignmentLevel" qual:id="tr_sa364_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa363</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa459</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C4 complement component was activated by MASP2. PMID:22949645 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re276"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21664989" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa365"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa363" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa365_in_0" /><qual:input qual:qualitativeSpecies="sa459" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa365_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa365" qual:transitionEffect="assignmentLevel" qual:id="tr_sa365_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa363</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa459</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C4 complement component was activated by MASP2. PMID:22949645 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re276"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21664989" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa367"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa366" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa367_in_0" /><qual:input qual:qualitativeSpecies="sa358" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa367_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa367" qual:transitionEffect="assignmentLevel" qual:id="tr_sa367_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa366</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa358</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C2 complement component was activated by MASP1. PMID:10946292 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re338"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10946292" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqmodel:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa368"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa366" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa368_in_0" /><qual:input qual:qualitativeSpecies="sa358" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa368_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa368" qual:transitionEffect="assignmentLevel" qual:id="tr_sa368_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa366</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa358</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C2 complement component was activated by MASP1. PMID:10946292 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re338"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10946292" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqmodel:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa387"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa480" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa387_in_0" /><qual:input qual:qualitativeSpecies="sa391" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa387_in_1" /><qual:input qual:qualitativeSpecies="sa365" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa387_in_2" /><qual:input qual:qualitativeSpecies="sa385" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa387_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa387" qual:transitionEffect="assignmentLevel" qual:id="tr_sa387_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa480</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa391</ci><cn type="integer">1</cn></apply><apply><and /><apply><eq /><ci>sa365</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa385</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19). Skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3) were examined. The pattern of COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils. No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent. These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the alternative and lectin-based complement pathways. PMID: 32299776 </p> <p>There was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined. PMID: 32299776 </p> <p>C4 is activated by enzymatic cleavage into C4a and C4b that can bind covalently to proteins or carbohydrates through a thioester bond. C4b is cleaved successively by factor I (CFB) leaving first iC4b and then C4d bound to the membrane. PMID:19362461 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re325"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32299776" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re308"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32299776" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re288"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19362461" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa388"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa387" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa388_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa388" qual:transitionEffect="assignmentLevel" qual:id="tr_sa388_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa387</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Extensive C4d deposition localized to the interalveolar septal capillaries and in microvasculature was then demonstrated in covid-19 patients. PMID:32299776 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re289"> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19362461" /> </rdf:Bag> </bqmodel:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa389"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa388" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa389_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa389" qual:transitionEffect="assignmentLevel" qual:id="tr_sa389_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa388</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The C4d deposits in lung transplants were associated with septal capillary necrosis and deposition of IgG, C1q, C3, and or C5b-9. PMID:19362461 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re361"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19362461" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa390"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa32" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa390_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa390" qual:transitionEffect="assignmentLevel" qual:id="tr_sa390_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>csa32</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The pulmonary findings of covid-19 cases were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways in covid-19 patients with microvascular injury and thrombosis. PMID: 32299776 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re292"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19362461" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa394"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa398" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa394_in_0" /><qual:input qual:qualitativeSpecies="sa480" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa394_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa394" qual:transitionEffect="assignmentLevel" qual:id="tr_sa394_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa398</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa480</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. PMID: 32336612 The role of ACE2 active‐site residues was explored by site‐directed mutagenesis. Arg273 was found to be critical for substrate binding such that its replacement causes enzyme activity to be abolished. Although both His505 and His345 are involved in catalysis, it is His345 and not His505 that acts as the hydrogen bond donor/acceptor in the formation of the tetrahedral peptide intermediate. The difference in chloride sensitivity between ACE2 and ACE was investigated, and the absence of a second chloride‐binding site (CL2) in ACE2 confirmed. Thus ACE2 has only one chloride‐binding site (CL1) whereas ACE has two sites. PMID: 16008552 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re304"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:16008552" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa395"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa17" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa395_in_0" /><qual:input qual:qualitativeSpecies="sa498" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa395_in_1" /><qual:input qual:qualitativeSpecies="csa25" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa395_in_2" /><qual:input qual:qualitativeSpecies="sa499" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa395_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa395" qual:transitionEffect="assignmentLevel" qual:id="tr_sa395_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>sa498</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa499</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>csa17</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa25</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Fibrin formation involves thrombin-mediated proteolytic cleavage and removal of N-terminal fibrinopeptides from the Aα and Bβ chains.PMID: 28228446 Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation.PMID: 6282863 The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. PMID:2117226 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re234"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6282863" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28228446" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2117226" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqmodel:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa397"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa402" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa397_in_0" /><qual:input qual:qualitativeSpecies="sa198" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa397_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa397" qual:transitionEffect="assignmentLevel" qual:id="tr_sa397_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa402</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa198</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Bradykinin concentrations and the ratio of bradykinin to its stable metabolite BK1–5 (RPPGF) were significantly increased in patients presenting with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema compared to ACE inhibitor-treated controls. PMID: 30036596 ACE catalyses degradation of Bradykinin in human plasma. PMID:10749699 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re374"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10969042" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa400"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa194" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa400_in_0" /><qual:input qual:qualitativeSpecies="sa394" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa400_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa400" qual:transitionEffect="assignmentLevel" qual:id="tr_sa400_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa194</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa394</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1-7 (Ang 1-7) which opposes the actions of Ang II. PMID:22536270 ACE2 metabolizes ANG II to Ang 1-7 in the kidney at neutral and basic pH, while prolylcarboxypeptidase catalyzes the same reaction at acidic pH. PMID:23392115 The entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. PMID: 32336612 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re307"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23392115" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa402"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa11" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa402_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa402" qual:transitionEffect="assignmentLevel" qual:id="tr_sa402_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>csa11</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Factor XIIa converts prekallikrein to kallikrein. PMID: 6768384 Kallikrein digests KNG1 to release bradykinin. PMID: 4627469 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#CDMT00119"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6768384" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:4627469" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa407"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa402" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa407_in_0" /><qual:input qual:qualitativeSpecies="sa198" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa407_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa407" qual:transitionEffect="assignmentLevel" qual:id="tr_sa407_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa402</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa198</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Bradykinin concentrations and the ratio of bradykinin to its stable metabolite BK1–5 (RPPGF) were significantly increased in patients presenting with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema compared to ACE inhibitor-treated controls. PMID: 30036596 ACE catalyses degradation of Bradykinin in human plasma. PMID:10749699 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re374"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10969042" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa408"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa390" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa408_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa408" qual:transitionEffect="assignmentLevel" qual:id="tr_sa408_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa390</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>C5b-9 membrane attack complex mediates endothelial cell apoptosis in experimental glomerulonephritis. PMID:10807586 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re360"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10807586" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa409"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa390" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa409_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa409" qual:transitionEffect="assignmentLevel" qual:id="tr_sa409_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa390</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The involvement of MAC in the intravascular release of vWf and aggregation of platelets in organ allografts has been demonstrated by experiments in C6 deficient rats. PMID:19362461 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re359"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19362461" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa410"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa207" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa410_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa410" qual:transitionEffect="assignmentLevel" qual:id="tr_sa410_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa207</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Patients with COVID-19 commonly show higher concentration of CRP. PMID:32171076 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re315"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32171076" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa411"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa499" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa411_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa411" qual:transitionEffect="assignmentLevel" qual:id="tr_sa411_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa499</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased in patients with COVID-19.PMID: 32367170 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re319"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32367170" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa417"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa459" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa417_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa417" qual:transitionEffect="assignmentLevel" qual:id="tr_sa417_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa459</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Extensive C4d deposition localized to the interalveolar septal capillaries and in microvasculature was then demonstrated in covid-19 patients. PMID: 32299776 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re339"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32299776" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa424"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa395" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa424_in_0" /><qual:input qual:qualitativeSpecies="sa425" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa424_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa424" qual:transitionEffect="assignmentLevel" qual:id="tr_sa424_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa395</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa425</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The fibrin monomers spontaneously polymerize end to end in a half-staggered,overlapping manner to form double-strandedfibrin protofibrils. PMID: 29096812 Fibrin strength is enhanced by factor XIIIa, a transglutaminase activatedby thrombin, which cross-links the D domains of adjacentfibrin monomers, as wellas thea-chains of opposing monomers to for D-dimer and a-polymers, respectively. PMID: 7577232 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re345"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29096812" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:7577232" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa430"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa42" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa430_in_0" /><qual:input qual:qualitativeSpecies="csa40" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa430_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa430" qual:transitionEffect="assignmentLevel" qual:id="tr_sa430_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>csa42</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa40</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Human glycoprotein VI binds to immobilized fibrinogen and show that this contributes to platelet spreading and platelet aggregation under flow. PMID: 29472360 </p> <p>GPVI and α2β1 to primary hemostasis confirm that collagen binding by VWF, GPVI, and α2β1 have major roles in thrombus formation. PMID: 25051961 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re356"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29472360" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re353"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25051961" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa441"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa484" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa441_in_0" /><qual:input qual:qualitativeSpecies="sa483" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa441_in_1" /><qual:input qual:qualitativeSpecies="sa430" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa441_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa441" qual:transitionEffect="assignmentLevel" qual:id="tr_sa441_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa484</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa483</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa430</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Angiotensin II via AT1 receptor accelerates arterial thrombosis. PMID:16391415 </p> <p>Ang-(1-7) inhibited thrombus formation in Mas+/+ mice. This effect was abolished in Mas-/-mice. PMID:18026570 Acute or chronic oral treatment with Ang-(1-7)-CyD promoted an antithrombotic effect (measured by thrombus weight; all values are, respectively, untreated vs. treated animals) in spontaneously hypertensive rats (acute: 2.86 ± 0.43 mg vs. 1.14 ± 0.40 mg; chronic: 4.27 ± 1.03 mg vs. 1.39 ± 0.68 mg). This effect was abolished in Mas-knockout mice (thrombus weight in Mas wild-type: 0.76 ± 0.10 mg vs. 0.37 ± 0.02 mg; thrombus weight in Mas-knockout: 0.96 ± 0.11 mg vs. 0.87 ± 0.14 mg). PMID:21789389 </p> <p>By using high-resolution intravital imaging techniques and hydrodynamic analyses, it was shown that platelet aggregation is primarily driven by changes in blood flow parameters (rheology), with soluble agonists having a secondary role, stabilizing formed aggregates. It was found that in response to vascular injury, thrombi initially develop through the progressive stabilization of discoid platelet aggregates. Analysis of blood flow dynamics revealed that discoid platelets preferentially adhere in low-shear zones at the downstream face of forming thrombi, with stabilization of aggregates dependent on the dynamic restructuring of membrane tethers. These findings provide insight into the prothrombotic effects of disturbed blood flow parameters and suggest a fundamental reinterpretation of the mechanisms driving platelet aggregation and thrombus growth. PMID: 19465929 GPVI and α2β1 to primary hemostasis confirm that collagen binding by VWF, GPVI, and α2β1 have major roles in thrombus formation. PMID: 25051961 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re369"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:16391415" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re365"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:18026570" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21789389" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re355"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25051961" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19465929" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa459"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa480" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa459_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa459" qual:transitionEffect="assignmentLevel" qual:id="tr_sa459_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa480</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>MBL2 interacts with MASP2. PMID:11290788 These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the alternative and lectin-based complement pathways. PMID:32299776 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re274"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:11290788" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32299776" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa483"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa400" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa483_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa483" qual:transitionEffect="assignmentLevel" qual:id="tr_sa483_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa400</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Specific binding of Ang-(1-7) was observed in Mas+/+ mouse platelets. No Ang-(1-7) binding was observed in Mas-/- mice. PMID:18026570 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re364"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:18026570" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa484"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa194" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa484_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa484" qual:transitionEffect="assignmentLevel" qual:id="tr_sa484_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa194</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Angiotensin II binds to AT1 receptor in human platelets. PMID: 8158359 AT1 receptor activation requires interaction of Phe8 side chain of Ang II with His256, which is achieved by docking the alpha-COOH group of Phe8 to Lys199. PMID: 7499361 The docking of Arg2 of angiotensin II with Asp281 of AT1 receptor is essential for full agonism. PMID: 7759541 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re366"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8158359" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa485"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa37" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa485_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa485" qual:transitionEffect="assignmentLevel" qual:id="tr_sa485_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>csa37</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>SARS-2-S exploits ACE2 for entry. SARS-CoV-2 can use TMPRSS2 for S protein priming and camostat mesylate, an inhibitor of TMPRSS2, blocks SARS-CoV-2 infection of lung cells. PMID:32142651 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re373"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32142651" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:2697049" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa503"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa480" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa503_in_0" /><qual:input qual:qualitativeSpecies="sa194" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa503_in_1" /><qual:input qual:qualitativeSpecies="sa521" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa503_in_2" /><qual:input qual:qualitativeSpecies="sa519" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa503_in_3" /><qual:input qual:qualitativeSpecies="sa527" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa503_in_4" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa503" qual:transitionEffect="assignmentLevel" qual:id="tr_sa503_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa480</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa194</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa521</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa519</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa527</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Aldosterone plasmatic concentration was increased in group of patients with COVID-19 associated acute kindney injury (AKI) compared with COVID-19 patients without AKI. PMID:32565254 The production of aldosterone by isolated canine zona glomerulosa cells was measured after the incubation of cell suspensions with angiotensin II and ACTH, and during changes in extracellular potassium concentration. PMID:173529 The stimulation of aldosterone secretion is mediated via the type 1 AI1 (ATl) receptor coupled to polyphosphoinositidase C, and this response is accompanied by an increase in Ca2+ in human NCI-H295 adrenocortical carcinoma cells. PMID:8404594 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re376"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8404594" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:173529" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9615" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32565254" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa509"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa503" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa509_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa509" qual:transitionEffect="assignmentLevel" qual:id="tr_sa509_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa503</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Aldoscterone was translocated from exreacellular space into cytoplasm. PMID:18202152 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re379"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8202152" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa516"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa509" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa516_in_0" /><qual:input qual:qualitativeSpecies="sa519" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa516_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa516" qual:transitionEffect="assignmentLevel" qual:id="tr_sa516_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa509</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa519</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Alodosterone binds to NR3C receptor. PMID:21349712 The mRNA expression of MR (Nr3c2) in the renal medulla was 40% lower in Agtr1a-/- compared to WT mice, and was unaffected by aldosterone in either group. PMID:27045029 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re382"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:21349712" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:7045029" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa518"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa509" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa518_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa518" qual:transitionEffect="assignmentLevel" qual:id="tr_sa518_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa509</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed in Agtr1a-/- mice. PMID:27045029 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re394"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27045029" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa519"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa194" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa519_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa519" qual:transitionEffect="assignmentLevel" qual:id="tr_sa519_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa194</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms></qual:transition><qual:transition qual:id="tr_sa521"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa531" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa521_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa521" qual:transitionEffect="assignmentLevel" qual:id="tr_sa521_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa531</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>The patients with COVID-19 were classified as having severe hypokalemia (plasma potassium less then3 mmol/L), hypokalemia (plasma potassium 3-3.5 mmol/L), and normokalemia (plasma potassium more then 3.5 mmol/L). PMID:32525548 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re398"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32525548" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa529"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa516" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa529_in_0" /><qual:input qual:qualitativeSpecies="sa519" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa529_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa529" qual:transitionEffect="assignmentLevel" qual:id="tr_sa529_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa516</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa519</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Acute administration of aldosterone in rats increased the density of fibrin net and platelet aggregates in clots as well as reduced fibrinolysis. These effects were observed within 10 min and were partially suppressed by eplerenone. Moreover, acute administration of aldosterone in mice enhanced platelet accumulation at the site of endothelial injury induced by laser and increased the area of irreversibly activated platelets in FeCl3-induced thrombus. These results demonstrate that aldosterone acutely affects platelets, coagulation, and fibrinolysis, leading to an enhanced thrombosis. The aldosterone effects were mediated partially via a mineralocorticoid receptor. The mechanism seems to involve non-genomic signaling since the effects were observed within a few minutes of aldosterone administration. PMID:31655164 </p> <p>AT 1 blockade with valsartan significantly reduced ALDO-induced thrombosis expressed as a reduced thrombus mass and diminished the incidence of thrombosis. Valsartan reduced the ALDO-induced changes in bleeding time and platelet adhesion, as well as in coagulation, fibrinolysis, and NO metabolite levels. The effect of AT 1 blockade in ALDO-induced thrombosis was similar to the effect of MR blockade. However, dual blockade of AT 1 and MR showed no additional benefit. ALDO prothrombotic action is partially mediated via AT 1 receptor in the mechanism involving enhanced platelet activation, induced coagulation, impaired fibrinolysis and reduced NO bioavailability. PMID:26709040 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re392"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:3165516" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re393"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26709040" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa530"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa509" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa530_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa530" qual:transitionEffect="assignmentLevel" qual:id="tr_sa530_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa509</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed in Agtr1a-/- mice. PMID:27045029 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re395"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27045029" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa531"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa480" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa531_in_0" /><qual:input qual:qualitativeSpecies="sa503" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa531_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa531" qual:transitionEffect="assignmentLevel" qual:id="tr_sa531_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa480</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa503</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body><p>Severe acute respiratory syndrome coronavirus 2 has caused a global outbreak of coronavirus disease 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 binds angiotensin-converting enzyme 2 of the rennin-angiotensin system, resulting in hypokalemia. PMID:32525548 </p> <p>Hypokalemia is found in 9-37% of all cases of PA with a predominance in patients with aldosterone producing adenoma. PMID:32252108 </p> </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re396"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32525548" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re399"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32252108" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition></qual:listOfTransitions></model></sbml>