Mechanism of factor VIIa-dependent coagulation in hemophilia blood.
Butenas S, Brummel KE, Branda RF, Paradis SG, Mann KG
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The mechanism of inducing hemostasis by factor VII (FVII) in hemophilia patients with inhibitors is not fully understood. Tissue factor (TF) and FVII are required to form a small concentration of thrombin (initiation phase) followed by increased activation of clotting factors and formation of a solid clot (propagation phase). This paper studies a model for thrombin generation by using varying concentrations of FVII and TF in normal blood as well as synthetic hemophilia A and B models. FVIIa-TF complex is at least 5-6×103 more efficient than FVII alone in initiating the coagulation cascade. Addition of FVIIa beyond the saturation of TF does not shorten clotting time and has no effect on the parameters of thrombin generation. However, the mechanism by which high concentration of rFVIIa maintain hemostasis and accelerates platelet activation in hemophiliacs remains not fully understood.
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