The influence of infusions of 1-desamino-8-D-arginine vasopressin (DDAVP) in vivo on thrombin generation in vitro.
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 less than 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 less than 0.001). T50 shortened from 78.5 and 76.0 to 62.5, 60.0 and 58.5 s at times 15 (p less than 0.01), 30 (p less than 0.001) and 60 (p less than 0.001) min. FVIII:C correlated inversely with lag and T50 (r = -0.847, p less than 0.001, r = -0.826, p less than 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.
Ibbotson
S H
SH
Academic Unit of Medicine, General Infirmary, Leeds, United Kingdom.
Davies
J A
JA
Grant
P J
PJ
D001777:Blood Coagulation / Q000187:drug effects*; D002863:Chromogenic Compounds; D003201:Computers; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage*; D004151:Dipeptides; D006801:Humans; D007262:Infusions, Intravenous; D012016:Reference Values; D013917:Thrombin / Q000096:biosynthesis*
D002863:Chromogenic Compounds; D004151:Dipeptides; C021129:S 2238; D013917:Thrombin; D003894:Deamino Arginine Vasopressin