A cell-based model of coagulation and the role of factor VIIa

Blood Rev. 2003 Sep:17 Suppl 1:S1-5. doi: 10.1016/s0268-960x(03)90000-2.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Blood Coagulation*
  • Blood Platelets / physiology
  • Factor VIIa / physiology*
  • Factor VIIa / therapeutic use
  • Hemophilia A / drug therapy
  • Hemostasis / drug effects
  • Humans
  • Monocytes / physiology

Substances

  • Factor VIIa