Hemophilic Synovitis: Factor VII and the Potential Role of Extravascular Factor VIIa

Abstract 

The initiation of coagulation via tissue factor/factor VIIa is relatively weak in normal synovium and joint tissues, so that hemophilic patients with additional deficiency of the intrinsic pathway of coagulation are especially at risk for joint bleeding and the development of hemophilic synovitis. The inflamed joint that results from recurrent bleeding-induced injury, however, may be an environment in which pharmacologic doses of factor VIIa have potentially greater procoagulant action than in the uninjured joint. There is accumulating evidence suggesting that coagulation factors in the extravascular space, and not only circulating plasma factors, have the potential to contribute to hemostatic protection of joints. The potential role of extravascular factor VIIa is considered.

Abbreviations: TF, tissue factor, FVIIa, activated Factor VII, rFVIIa, recombinant activated factor VII, EPCR, endothelial protein C receptor, TFPI, tissue factor pathway inhibitor, I.A., intraarticular, I.V., intravenous, AAV, adeno-associated virus

Keywords: Factor VII, Factor VIIa, Hemostasis, Tissue-specific, Extravascular, Adeno-associated virus, Factor IX, Factor VIII