The Influence of Infusions of 1-Desamino-8-D-Arginine Vasopressin (DDAVP) In Vivo on Thrombin Generation In Vitro

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.

• References

• 1 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Ineson JD, Mellows S, Miller GJ, North WRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; ii: 533-537
• 2 Gorral RJM, Webber RG, Frier BM. Increase in coagulation factor VIII activity in man following acute hypoglycaemia: mediation via an adrenergic mechanism. Br J Haematol 1980; 22: 301-305
• 3 Paton RC. Haemostatic changes in diabetic coma. Diabetologia 1981; 21: 172-177
• 4 Grant PJ, Tate GM, Davies JA, Williams NS, Prentice CRM. Intraoperative activation of coagulation – a stimulus to thrombosis mediated by vasopressin?. Thromb Haemostas 1986; 55: 104-107
• 5 Ibbotson SH, Tate GM, Hampton KK, Davies JA. Influence of increasing levels of high purity factor VIII on thrombin generation in-vitro. Clin Sci 1990; 79 (suppl 23) 15 (abs)
• 6 Bern MM, Cassani NP, Horton J, Rand L, Davis G. Changes in fibrinolysis and factor VIII coagulant antigen and ristocetin cofactor in diabetes mellitus. Thromb Res 1980; 19: 831-839
• 7 Dornan TL, Thymes IL, Dederholm WilliamsSA, Rizza CR, Pepys MB, Bron AJ, Turner RC. Plasma haemostatic factors and diabetic retinopathy. Eur J Clin Invest 1983; 13: 231-235
• 8 Fuller H. Haemostatic function tests associated with diabetic retinopathy. Horm Metab Res 1981; II: 59-62
• 9 MacGregor IR, Roberts EM, Prowse CV, Broomhead AF, Ozolins M, Litka P. Fibrinolytic and haemostatic responses to desamino-D-arginine vasopressin (DDAVP) administered by intravenous and subcutaneous routes in healthy subjects. Thromb Haemostas 1988; 59 (1) 34-39
• 10 Mannucci PM. Desmopressin: A nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988; 72: 1449-1455
• 11 Mannucci PM. Desmopressin (DDAVP) for treatment of disorders of hemostasis. In: Progress in Haemostasis and Thrombosis. Grune & Strattan; 1986: 19-45
• 12 Hemker HC, Willems GM, Béguin S. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb Haemostas 1986; 56: 9-17
• 13 Ibbotson SH, Grant PJ, Kerry R, Findlay VS, Prentice CRM. The influence of infusions of 1-desamino-8-arginine vasopressin (DDAVP) in-vivo on the anticoagulant effect of recombinant hirudin (CGP39393) in-vitro. Thromb Haemostas 1991; 65: 64-66
• 14 Hardisty RM, MacPhearson JC. A one stage FVIII AHG assay and its use on venous and capillary plasma. Thromb Diathes Haemorrh 1962; 7: 215-219
• 15 Cohen RJ, Epstein SC, Cohen LS, Dennis LH. Alterations of fibrinolysis and blood coagulation induced by exercise and the role of beta adrenergic stimulation. Lancet 1968; ii: 1264-1266
• 16 Meade TW, Chakrabarti R, Haines AP, North WRS, Stirling Y, Thompson SG. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; i: 1050-1054