Heparin reversal by protamine in humans--complement, prostaglandins, blood cells, and hemodynamics

Abstract

Fourteen noncardiac surgical patients received heparin (10,000 IU), which was neutralized by 100 mg protamine injected within 2 min during steady-state anesthesia. After protamine application, plasma complement C3a, thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and KH2PGF2 alpha increased significantly, whereas prostacyclin (6-keto-PGF2 alpha) levels did not change. This mediator response was associated with transient leukopenia and thrombocytopenia. Arterial pressure, pulmonary arterial pressure, and transpulmonary pressure gradient increased significantly. Heart rate, cardiac output, pulmonary capillary wedge pressure, and arterial PO2 remained constant. Positive correlations of plasma C3a were observed with pulmonary leukosequestration and plasma TxB2. Inverse correlations of C3a were noted with the counts of leukocytes and of platelets. A positive correlation was found between TxB2 and pulmonary arterial pressure. Our results indicate that marked activation of the complement system and the cyclooxygenase pathway is common after heparin reversal by protamine in anesthetized patients. This is in contrast to previous human studies performed after cardiopulmonary bypass but agrees well with results obtained in animal experiments. The mediator response in our patients, however, was not accompanied by hemodynamic instability, suggesting appropriate compensatory mechanisms.