PROTAMINE REVERSAL OF HEPARIN AFFECTS PLATELET-AGGREGATION AND ACTIVATED CLOTTING TIME AFTER CARDIOPULMONARY BYPASS

Bleeding after cardiopulmonary bypass (CPB) is related to multiple fac tors. Excess protamine weakens clot structure and decreases platelet f unction; therefore, an increased activated clotting time (ACT) after p rotamine reversal of heparin may be misinterpreted as residual heparin anticoagulation. We evaluated the effects of protamine, recombinant p latelet factor 4 (rPF4), and hexadimethrine on ACT in blood obtained a fter CPB. Ln addition, we examined the effect of protamine on in vitro platelet aggregation. Incremental doses of protamine, rPF4, and hexad imethrine were added to heparinized blood from CPB, and ACTs were perf ormed. Incremental concentrations of protamine were added to hepariniz ed platelet-rich plasma, and aggregometry was induced by adenosine dip hosphate (ADP) and collagen. The mean heparin concentration at the end of CPB was 3.3 U/mL. Protamine to heparin ratios >1.3:1 produced a si gnificant prolongation of the ACT that was not seen with rPF4 and was observed only with 5:1 hexadimethrine to heparin ratios. ADP-induced p latelet aggregation was reduced with protamine administration greater than or equal to 1.3:1. Excessive protamine reversal of heparin prolon gs ACT and alters ADP-induced platelet aggregation in a dose-dependent manner in vitro. Additional protamine administered to treat a prolong ed ACT may further increase clotting time, reduce platelet aggregation , and potentially contribute to excess bleeding after CPB. Implication s: We found that excess protamine prolonged the activated clotting tim e and altered platelet function after cardiopulmonary bypass, whereas heparin antagonists, such as recombinant platelet factor 4 and hexadim ethrine, exhibited a wider therapeutic range without adversely affecti ng the activated clotting time. Approaches to avoid excess protamine o r use of alternative heparin antagonists after cardiopulmonary bypass may be beneficial.