Effect of high physiological levels of factor VIII:C and factor V on rate of generation of thrombin activity in vitro

Increased plasma FVIII:C concentrations occur in several conditions, including diabetes, but whether this leads to clinically relevant hypercoagulability is uncertain. Accordingly, we investigated the effects of increasing FVIII:C levels on coagulation in vitro using a computer-assisted measurement of thrombin activity. Defibrinated plasma was activated with kaolin, thrombin activity measured using the chromogenic substrate S2238 and time to generate 50% maximal thrombin activity (T50) recorded in seconds. Increasing FVIII:C levels from 100 to 350% significantly reduced T50 (mean +/- SD) from 91 +/- 3 to 64 +/- 6.2 s (P <0.001, n = 6), and T50 correlated inversely with FVIII:C (r = -0.884, P <0.001, n = 36). Increasing FV concentrations resulted in an additive effect with high FVIII:C levels on the rate of thrombin generation. The results showed that increasing plasma FVIII:C and FV concentrations accelerate rate of generation of thrombin activity independently, and in an additive manner.