FRAGMIN(TM) (LMWH) VS HEPARIN FOR ANTICOAGULATION DURING IN-VITRO RECYCLING OF HUMAN BLOOD IN CARDIOPULMONARY BYPASS CIRCUITS - DOSE-DEPENDENCE AND MECHANISMS OF CLOTTING

Low-molecular-weight heparin (LMWH) (Fragmin (TM)) vs heparin was stud ied in vitro in order to investigate its antithrombotic efficacy in th e isolated thrombogenic link of cardiopulmonary bypass (CPB). Fresh hu man blood (400 ml) with various dosages of the anticoagulant was recyc led in a CPB circuit for 120 min. The standard dosage of heparin (1500 IU, n = 6) was compared with a lower dosage (1000 IU, n = 3) and seve ral dosages of Fragmin (TM) (IU anti-FXa): 750 (n = 1), 1500 (n = 3), 2100 (n = 4) and 2500 (n = 3). Clotting occurred in three Fragmin (TM) experiments at dosages of 750, 1500 and 2100 IU. This was associated with short activated clotting time (ACT) and activated partial thrombo plastin time (aPTT) but was independent of the levels of anti-FXa, FVI II, von Willebrand factor and prothrombin complex. It was concluded th at at least twice the dose of Fragmin (TM) (anti-FXa), compared with h eparin, was required, suggesting that thrombin inhibition is crucial f or the antithrombotic efficacy of heparin in CPB circuits. Absence of fibrinolytic markers suggests that the well known enhancement of fibri nolysis often seen during CPB, is not due to heparin interaction with normally circulating blood components, but rather to interaction with the vessel walls or to the surgical trauma itself.