THE EFFECT OF PLASMA ANTITHROMBIN CONCENTRATION ON THROMBIN GENERATION AND FIBRIN GEL STRUCTURE

Congenital deficiency of antithrombin (AT) is associated with thrombot ic events and AT consumption occurs in some severe disorders anti afte r treatment with heparin. The aim of this study was to investigate whe ther variations in the level of plasma AT modify thrombin generation a nd the fibrin formation process after the intrinsic coagulation mechan ism is triggered. Normal plasma was depleted of AT by immunoadsorption on CNBr-Sepharose coupled with the anti-AT-IgG fraction of antiserum. The AT-depleted plasma was reconstituted with AT (between 0.33 and 1. 5 AT units per ml). Thrombin generation was measured as the developmen t of thrombin-antithrombin complexes (TAT). The lag phase preceding fi brin formation depended on the concentration of AT. The short lag phas e was seen in completely AT-depleted plasma and the long in plasma wit h 1.5 AT units pel mi. TAT generation, determined in parallel consecut ive samples, showed that the late at which thrombin was generated was inverse to the AT concentration in plasma. The network structure of hy drated fibrin gels in the clotted plasma was studied by measuring the wavelength dependence of gel turbidity. The mass/length ratio value, - i.e. the thickness of fiber strands and porosity of the gel increased with increasing AT concentrations. It is concluded that plasma AT regu lates the rate of prothrombin-thrombin conversion, the clotting time a nd the consequently network structure of the fibrin gel.