Enoxaparin suppresses thrombin formation and activity during cardiopulmonary bypass in baboons

Objective: This study tests the hypotheses that enoxaparin, a low molecular weight heparin and potent inhibitor of factor Xa, alone or in combination with standard heparin, inhibits thrombin formation and activity and modulat es complement activation and neutrophil elastase release during cardiopulmo nary bypass in baboons, Methods: After preliminary studies to determine dos es and possible species differences to anticoagulants and protamine, 27 ane sthesized baboons had normothermic cardiopulmonary bypass with standard, un fractionated, porcine intestinal heparin, enoxaparin, or a combination of h eparin and enoxaparin, Protamine in appropriate doses was used to reverse a nticoagulation, Blood samples were obtained at 6 time points. Activated clo tting times were monitored; template bleeding times were measured before an d up to 24 hours after cardiopulmonary bypass. Results: Hemodynamic measure ments were not affected by the anticoagulant, Activated clotting times rema ined above 400 seconds throughout bypass, and no clots were observed. The a nticoagulant did not alter platelet count, aggregation to adenosine diphosp hate, release of P-thromboglobulin, release of neutrophil elastase, or comp lement C3b/c and C4b/c. Enoxaparin alone, but not in combination, significa ntly reduced plasma levels of prothrombin fragment F1.2, fibrinopeptide A, and thrombin-antithrombin complexes but prolonged template bleeding times f or more than 24 hours. Conclusion: Enoxaparin significantly reduces thrombi n formation and activity during cardiopulmonary bypass but does not suppres s complement activation and neutrophil elastase release and is not adequate ly reversed by protamine after bypass.