Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Curr Opin Hematol. 2011 Sep;18(5):338-42. doi: 10.1097/MOH.0b013e3283497ebc.
Factor V plays an essential role in hemostasis and has a profound influence on thrombin generation. The aim of this review is to highlight recent advances in our understanding of the biology of factor V which shed light on the variable bleeding tendencies in severe factor V deficiency. Furthermore, new mechanistic insights responsible for maintaining factor V as an inactive procofactor will be discussed.
The bleeding manifestation of severe factor V-deficient patients varies dramatically. Phenotypic modifiers of the bleeding predisposition in these patients have recently been identified. These include platelet factor V and, surprisingly, plasma tissue factor pathway inhibitor, which is significantly reduced in these patients. An important step in robust thrombin generation is the activation of factor V to factor Va. In a mechanism distinct from factor VIII, factor V activation involves proteolytic removal of inhibitory and conserved sequences from the large central B domain which exposes binding sites for factor Xa and possibly prothrombin. Taking advantage of this mechanism, certain Australian snakes have a unique form of factor V in their venom with these inhibitory sequences removed, thereby creating a potent constitutively active procoagulant cofactor.
Basic biochemical and clinical studies continue to move our understanding of factor V forward. It is apparent that there is much to be learned about parahemophilia and factor V activation, two seemingly well studied areas of research. A full understanding of each may provide unanticipated insights into ways to modulate factor V/Va function for therapeutic benefit.
因子 V 在止血中起着至关重要的作用，对凝血酶生成有深远影响。本文旨在强调我们对因子 V 生物学的最新认识，这些认识揭示了严重因子 V 缺乏症患者出血倾向的多变性。此外，还将讨论负责维持因子 V 作为无活性前体酶的新机制见解。
严重因子 V 缺乏症患者的出血表现差异很大。这些患者的出血倾向表型修饰因子最近已被确定。这些因子包括血小板因子 V，以及令人惊讶的是，血浆组织因子途径抑制剂在这些患者中显著降低。强大的凝血酶生成的重要步骤是因子 V 向因子 Va 的激活。在一种与因子 VIII 不同的机制中，因子 V 的激活涉及从大的中央 B 结构域中去除抑制性和保守序列，从而暴露因子 Xa 和可能的凝血酶的结合位点。利用这一机制，某些澳大利亚蛇类在其毒液中具有一种独特形式的因子 V，去除了这些抑制性序列，从而形成了一种有效的、组成型激活的促凝血辅因子。
基础生化和临床研究继续推动我们对因子 V 的理解。显然，还有很多关于副血友病和因子 V 激活的知识需要学习，这是两个看似研究充分的领域。充分了解这两个领域可能会为我们提供意想不到的方法来调节因子 V/Va 的功能，以达到治疗效果。
