| http://purl.uniprot.org/citations/30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30026184 | http://www.w3.org/2000/01/rdf-schema#comment | "Joint bleeds are common in congenital hemophilia but rare in acquired hemophilia A (aHA) for reasons unknown. To identify key mechanisms responsible for joint-specific bleeding in congenital hemophilia, bleeding phenotypes after joint injury and tail transection were compared in aHA wild-type (WT) mice (receiving an anti-factor VIII [FVIII] antibody) and congenital HA (FVIII-/-) mice. Both aHA and FVIII-/- mice bled severely after tail transection, but consistent with clinical findings, joint bleeding was notably milder in aHA compared with FVIII-/- mice. Focus was directed to thrombin-activatable fibrinolysis inhibitor (TAFI) to determine its potentially protective effect on joint bleeding in aHA. Joint bleeding in TAFI-/- mice with anti-FVIII antibody was increased, compared with WT aHA mice, and became indistinguishable from joint bleeding in FVIII-/- mice. Measurements of circulating TAFI zymogen consumption after joint injury indicated severely defective TAFI activation in FVIII-/- mice in vivo, consistent with previous in vitro analyses in FVIII-deficient plasma. In contrast, notable TAFI activation was observed in aHA mice, suggesting that TAFI protected aHA joints against bleeding. Pharmacological inhibitors of fibrinolysis revealed that urokinase-type plasminogen activator (uPA)-induced fibrinolysis drove joint bleeding, whereas tissue-type plasminogen activator-mediated fibrinolysis contributed to tail bleeding. These data identify TAFI as an important modifier of hemophilic joint bleeding in aHA by inhibiting uPA-mediated fibrinolysis. Moreover, our data suggest that bleed protection by TAFI was absent in congenital FVIII-/- mice because of severely defective TAFI activation, underscoring the importance of clot protection in addition to clot formation when considering prohemostatic strategies for hemophilic joint bleeding."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2018-01-828434"xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/author | "Behrendt N."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/author | "Meijers J.C.M."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/author | "Declerck P.J."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/author | "Mosnier L.O."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/author | "Cooke E.J."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/author | "von Drygalski A."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/author | "Wyseure T."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/pages | "1593-1603"xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/title | "Defective TAFI activation in hemophilia A mice is a major contributor to joint bleeding."xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://purl.uniprot.org/core/volume | "132"xsd:string |
| http://purl.uniprot.org/citations/30026184 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30026184 |
| http://purl.uniprot.org/citations/30026184 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30026184 |
| http://purl.uniprot.org/uniprot/#_D3YW61-mappedCitation-30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30026184 |
| http://purl.uniprot.org/uniprot/#_B2RRC9-mappedCitation-30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30026184 |
| http://purl.uniprot.org/uniprot/#_B1AW26-mappedCitation-30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30026184 |
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| http://purl.uniprot.org/uniprot/#_Q06194-mappedCitation-30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30026184 |
| http://purl.uniprot.org/uniprot/#_Q8BQ43-mappedCitation-30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30026184 |
| http://purl.uniprot.org/uniprot/#_Q684Q7-mappedCitation-30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30026184 |
| http://purl.uniprot.org/uniprot/#_Q9JHH6-mappedCitation-30026184 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30026184 |