Summary
To investigate the effect of increasing FVIII:C in-vivo on coagulation ex-vivo, DDAVP
was infused over 15 min in 10 volunteers and in-vitro thrombin generation measured.
FVIII:C rose from 0.42 and 0.43 IU/ml before DDAVP to 1.38, 1.73 and 1.78 IU/ml at
15, 30 and 60 min respectively (p <0.001).
A computer-assisted thrombin generation test was performed in defibrinated plasma
using chromogenic substrate, S2238. Time to reach 50% maximal thrombin activity (T50/s) and lag phase of thrombin generation (lag/s) were measured. Lag shortened from
75 and 60 s before to 45 s during and after infusion (p <0.001). T50 shortened from 78.5 and 76.0 to 62.5, 60.0 and 58.5 s at times 15 (p <0.01), 30 (p <0.001) and 60 (p <0.001) min. FVIII:C correlated inversely with lag and T50 (r = –0.847, p <0.001, r = –0.826, p <0.001, n = 10) respectively.
These findings show that acute elevations of FVIII:C in-vivo accelerate in-vitro thrombin
production. This work suggests that elevated FVIII:C levels in-vivo may be important
in thrombo-occlusive disease.
