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- W12932324 abstract "Protein C (PC) is the key component of a natural anticoagulant pathway that is activated on the surface of endothelial cells by thrombin bound to thrombomodulin. Activated protein C [APC] cleaves and inhibits membrane bound factor Va and factor VIIIa, which leads to specific and efficient downregulation of the coagulation pathway. In these reactions, protein S (PS) and intact factor V (FV) function as cofactors to APC. Inherited deficiencies of PC, PS, or antithrombin were until recently the major genetic causes of familial venous thrombophilia, but they were found in less than 5% to 10% of patients with thrombosis. The situation changed dramatically with the description in 1993 of resistance to APC as a major risk factor for venous thrombosis. Inherited APC resistance, which is found in 20% to 60% of patients with venous thrombosis, is caused by a single point mutation in the FV gene predicting substitution of arginine [R] at position 506 with a glutamine (Q). The mutation, which is the result of a founder effect, is common in Caucasians with 1% to 15% prevalence in the population, whereas it is not found in other human races. Mutated FV (FVR506Q, FV:Q506 or FV Leiden) has normal procoagulant properties but shows partial resistance to APC, which results in a hypercoagulable state conferring a lifelong increased risk of thrombosis. As a result of its high prevalence, the FV mutation is not uncommon among patients with other inherited defects such as deficiency of PS, PC, or antithrombin. Those having combined defects have a higher incidence of thrombosis, and it is now recognized that severe thrombophilia is a typical multigenetic disease. The high prevalence of the FVR506Q mutation and the availability of easy functional and genetic tests will profoundly influence the development of therapeutic and prophylactic regimens and will probably result in a decreased incidence of thromboembolic events." @default.
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- W12932324 date "1997-07-01" @default.
- W12932324 modified "2023-09-23" @default.
- W12932324 title "Resistance to activated protein C as risk factor for thrombosis: molecular mechanisms, laboratory investigation, and clinical management." @default.
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