A cell-based model of coagulation and the role of factor VIIa.
Our cell-based model of haemostasis replaces the traditional 'cascade' hypothesis, and proposes that coagulation takes place on different cell surfaces in three overlapping steps: initiation, amplification, and propagation. In highlighting the importance of cellular control during coagulation, the cell-based model allows a more thorough understanding of how haemostasis works in vivo, and sheds light on the pathophysiological mechanisms behind certain coagulation disorders. For instance, this model proposes that haemophilia involves a failure of platelet-surface FXa generation, leading to a lack of platelet-surface thrombin production. Our data suggest that high-dose FVIIa is able to bind weakly to activated platelets, independently of tissue factor, in order to generate sufficient amounts of FXa to support a burst bf thrombin generation in the absence of FIXa/FVIIIa. The considerable success of high-dose recombinant FVIIa (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen, Denmark) as a therapy for patients with haemophilia and inhibitors has led to its use in a growing number of alternative indications. We believe that even in the presence of the FIXa/FVIIIa complex, rFVIIa may be able to enhance both FXa and FIXa levels on the surface of activated platelets, thus increasing the production of thrombin.
Hoffman
Maureane
M
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27705, USA. Maureane.hoffman@med.va.gov
D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology; D015942:Factor VIIa / Q000502:physiology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000502:physiology
D015942:Factor VIIa