THROMBIN GENERATION DURING CARDIAC-SURGERY - IS HEPARIN THE IDEAL ANTICOAGULANT

Blood samples were collected from 43 patients undergoing elective card iac surgery to determine the extent of thrombin generation and inhibit ion in patients when receiving heparin while undergoing cardiopulmonar y bypass (CPB). Plasma prothrombin fragment F1 + 2 and thrombin-antith rombin III (TAT) levels were measured as markers of thrombin generatio n and inhibition, respectively. Both F1 + 2 and TAT levels increased s ignificantly during the course of CPB despite the heparin causing sign ificant systemic anticoagulation, i.e. the activated coagulation time (ACT) was prolonged to greater than 400 s throughout the entire surgic al procedure. The extent of thrombin generation increased with time on CPB but did not differ between patients receiving normothermic and hy pothermic cardioplegia during CPB. Furthermore, thrombin generation in creased following the neutralization of the heparin with protamine sul phate, and continued to be elevated significantly 24 h post surgery. T he observation that high dose heparin did not prevent thrombin generat ion during CPB, is consistent with previous experimental studies demon strating that thrombin bound to fibrin or other surfaces (e.g. the CPB conduit) is resistant to antithrombin III/heparin inhibition, and thu s able to facilitate further thrombin generation. The observation that thrombin generation continued to be elevated post surgery i.e. 24 h a fter neutralizing the heparin with protamine sulphate, suggests that t he high dose heparin did not inhibit effectively all of the thrombin t hat had been generated. Thus, CPB patients may be at risk not only of bleeding and other side-effects associated with the acute use of high dose heparin, but may also be at risk of further thrombosis-related ev ents either acutely or chronically.