Blood Coagulation Factors V and VIII: Molecular Mechanisms of Procofactor Activation

Bos M HA, Camire R M.  Blood Coagulation Factors V and VIII:  Molecular Mechanisms of Procofactor Activation:  Journal of Coagulation Disorders, July 2010; 2(2):  19-27

REVIEW ARTICLE

Mettine HA Bos¹ and Rodney M Camire^1,2

Affiliations: ¹Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA and ²School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA


ABSTRACT

A hallmark of hemostasis is that cells and proteins involved in the formation of a blood clot remain in a quiescent state and are only activated following an appropriate stimulus. The homologous proteins factors V (FV) and VIII (FVIII) cannot participate to any significant degree in their macromolecular enzyme complexes and are thus considered procofactors. Activity is generated following limited proteolysis, indicating that the conversion of the procofactors to factor Va and factor VIIIa must result in structural changes that impart cofactor function. The proteolytic events that lead to the activation of these proteins have been extensively characterized over the past three decades. However, a fundamental understanding of the mechanism(s) by which these proteins are kept as inactive procofactors and how specific bond cleavage facilitates the conversion to the active cofactor state is only starting to become known. These molecular processes undoubtedly play critical regulatory roles, evolved to maintain normal hemostasis since factor Va and factor VIIIa have a tremendous influence on thrombin generation. This review will detail our current understanding of the molecular process of procofactor activation and highlight structural features that play a major role in FV and FVIII activation.

Keywords: factor V, factor VIII, prothrombin activation, FX activation, procofactor, proteolytic activation, hemostasis

Correspondence: Rodney M Camire, Department of Pediatrics, Division of Hematology, The Children's Hospital of Philadelphia, 5018 Colket Translational Research Building, 3501 Civic Center Boulevard, Philadelphia, PA 19104, USA. Tel: +1 215 590 9968; Fax: +1 215 590 3660; e-mail: rcamire@mail.med.upenn.edu