Generation of thrombin activity in relation to factor VIII: C concentrations and vascular complications in Type 1 (insulin-dependent) diabetes mellitus

A possible association between plasma coagulant activity and the presence of vascular complications in patients with diabetes mellitus was studied by measuring the generation of thrombin in plasma of 20 control subjects and 50 diabetic patients classified according to the presence or absence of microvascular complications. Thrombin production was determined in defibrinated plasma using a semiautomated technique with measurement of thrombin activity using chromogenic peptide S2238. Values determined were the lag time to appearance of thrombin activity and time taken to generate 50% maximal thrombin activity. Thrombin activity was related to concentrations of coagulant factor VIII activity and fibrinopeptide A and these were correlated with HbA_1C levels. The median time to generate 50% maximal thrombin activity was not significantly reduced in diabetic patients compared with control subjects (53 vs 54 s, p=0.076) and there were no significant differences between patients with and without microvascular complications. There were no differences in median fibrinopeptide A concentrations between the diabetic and control subjects (1.5 vs 2.2 nmol/l, p=0.169).Time to 50% maximal thrombin activity correlated inversely with factor VIII: C concentrations in diabetic patients (r=-0.344, p=0.015, n=50) and both this and lag time correlated with factor VIII: C in diabetic patients and control subjects combined (r =-0.395, p<0.01; r = -0.327, p=0.006, n =70). Factor VIII: C concentrations increased with age of the subject and with HbA_1C concentrations. The results failed to show enhancement of coagulation in contact-activated diabetic plasma compared with control plasma and suggest that a relationship between high levels of factor VIII:C in diabetes and the development of microvascular complications is unlikely to be mediated through procoagulant activity in plasma.