Heparin resistance during cardiopulmonary bypass. The role of heparin pretreatment.

Resistance to heparin therapy during cardiopulmonary bypass (CPB) is an infrequent yet potentially catastrophic occurrence. Although the exact mechanism of heparin resistance remains unknown, prior exposure to heparin has been implicated as a possible etiologic factor. Of 46 patients undergoing CPB, a subgroup of eight patients requiring heparin treatment preoperatively were retrospectively identified to be at high risk for the development of heparin resistance. Seven of these patients were therapeutically given heparin preoperatively for complications of mitral valve disease. The remaining 38 patients served as a control, 12 patients requiring valvular procedures and 26 patients undergoing myocardial revascularization. Heparinization for CPB was achieved by giving serial heparin doses of 2 mg/kg until the activated clotting time (ACT) exceeded 400 seconds. The patients receiving heparin preoperatively exhibited a significantly lower ACT response (315.4 ± 58.1 seconds) after a heparin dose of 4 mg/kg than either the control valve (458.4 ± 106.7 seconds) or control coronary (442.2 ± 151.2 seconds) patients. Heparin sensitivity, which was determined by deriving the ACT response per unit of plasma heparin, was also significantly diminished in those patients who were pretreated with heparin. Upon further analysis, heparin resistance was not attributed to a difference in the plasma heparin levels, antithrombin III activity, clotting factors, fibrinogen concentration, or platelet count. The only predictive parameter for the development of heparin resistance in patients pretreated with heparin was a significantly lower baseline ACT. If a fixed heparinization protocol were used, patients receiving heparin in the preoperative interval would be at high risk for inadequate anticoagulation during CPB and would be prone to potentially lethal hemorrhagic and thrombotic sequelae. Therefore, those patients receiving heparin preoperatively require a detailed assessment of the clinical heparin effect prior to the safe institution of CPB.