Your browser version may not work well with NCBI's Web applications. More information here...
1: Blood Rev. 2004 Mar;18(1):1-15.Click here to read Links

Activation of factor VIII and mechanisms of cofactor action.

Fay PJ.

Departments of Biochemistry and Biophysics and Medicine, PO Box 712, University of Rochester School of Medicine, Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA. philip_fay@urmc.rochester.edu

The factor VIII procofactor circulates as a metal ion-dependent heterodimer of a heavy chain and light chain. Activation of factor VIII results from limited proteolysis catalyzed by thrombin or factor Xa, which binds the factor VIII substrate over extended interactive surfaces. The proteases efficiently cleave factor VIII at three sites, two within the heavy and one within the light chain resulting in alteration of its covalent structure and conformation and yielding the active cofactor, factor VIIIa. The role of factor VIIIa is to markedly increase the catalytic efficiency of factor IXa in the activation of factor X. This effect is manifested in a dramatic increase in the catalytic rate constant, k(cat), by mechanisms that remain poorly understood.

PMID: 14684146 [PubMed - indexed for MEDLINE]

Patient Drug Information