title: A new look at blood coagulation factor V.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA. rcamire@mail.med.upenn.edu
authors: Rodney M
authors: RM
authors: Camire
mesh_terms: D000818:Animals; D005165:Factor V / Q000235:genetics / Q000378:metabolism*; D005166:Factor V Deficiency / Q000235:genetics / Q000378:metabolism; D006801:Humans
chemical_list: D005165:Factor V