Coagulation factor V (FV), present in plasma and platelets, is indispensable to
thrombin formation, yet patients with undetectable plasma FV seldom experience major
bleeding. We used
thrombin generation assays to explore the role of platelet FV in 4 patients with severe congenital FV deficiency (3 with plasma FV clotting activity [FV:C] < 1%). When triggered with
tissue factor (TF) concentrations up to 50pM, platelet-poor plasma (PPP) from the patients with undetectable plasma FV showed no
thrombin generation, whereas platelet-rich plasma (PRP) formed
thrombin already at 1 to 5pM of TF.
Thrombin generation in PRP from the FV-deficient patients was enhanced to near-normal levels by platelet activators (
collagen or Ca(2+)-
ionophore) and could be completely suppressed by specific FV inhibitors, suggesting FV dependence. Accordingly, platelet FV
antigen and activity were measurable in all FV-deficient patients and platelet FVa could be visualized by Western blotting. Normalization of the
tissue factor pathway inhibitor (
TFPI) level, which is physiologically low in FV-deficient plasma, almost completely abolished
thrombin generation in PRP from the FV-deficient patients. In conclusion, patients with undetectable plasma FV may contain functional FV in their platelets. In combination with low
TFPI level, residual platelet FV allows sufficient
thrombin generation to rescue these patients from fatal
bleeding.