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.
Ibbotson
S H
SH
Academic Unit of Medicine, General Infirmary, Leeds, UK.
Tate
G M
GM
Davies
J A
JA
D001777:Blood Coagulation / Q000187:drug effects*; D004151:Dipeptides / Q000378:metabolism; D005165:Factor V / Q000494:pharmacology*; D005169:Factor VIII / Q000494:pharmacology*; D006801:Humans; D007616:Kaolin / Q000494:pharmacology; D007700:Kinetics; D008838:Microcomputers; D013268:Stimulation, Chemical; D013917:Thrombin / Q000096:biosynthesis*
D004151:Dipeptides; D007616:Kaolin; C021129:S 2238; D005165:Factor V; D005169:Factor VIII; D013917:Thrombin