LOW-MOLECULAR-WEIGHT HEPARIN (FRAGMIN(TM)) VERSUS HEPARIN FOR ANTICOAGULATION DURING CARDIOPULMONARY BYPASS IN OPEN-HEART-SURGERY, USING A PIG MODEL

Fragmin (TM) and heparin were studied in pigs during 120 min of cardiopulmonary bypass (CPB) and up to 240 min postoperatively, with respect to clotting, bleeding and the effects of protamine. Thirty-three pigs received bolus injections of 300IU/kg with or without additional dosage during CPB and with or without subsequent protamine sulphate. Doses of Fragmin (TM) 60% higher were necessary to prevent clotting. These had 100% higher anti-FXa levels but about 50% shorter activated coagulation time (ACT) compared with heparin. Anti-FXa increased with cumulative doses of heparin and Fragmin (TM) but ACT and activated partial thromboplastin time (aPTT) did not, indicating a larger loss of thrombin inhibition compared with anti-FXa in both drugs during CPB. Thrombin inhibition was crucial for prevention of clotting. Protamine efficiently normalized ACT in the Fragmin (TM) group but left a residual 20% anti-FXa, which did not increase the bleeding tendency. Fragmin (TM) could adequately be monitored with ACT and would be a safe alternative to heparin in CPB.