Low-dose protamine based on heparin-protamine titration method reduces platelet dysfunction after cardiopulmonary bypass

Objective: The heparin-protamine titration method that uses the Hepcon hemo stasis management system (Medtronic HemoTec Inc, Eaglewood, Cole) reduced b lood loss in cardiac surgery in previous reports, but the mechanism is not fully understood, This study tests the hypothesis that reduced protamine ad ministration preserves platelet function in human cardiac surgery. Methods: Platelet count, or-granule secretion, and aggregation to thrombin before a nd after cardiopulmonary bypass in human beings were evaluated, In the cont rol group (n = 14), a fixed dose of protamine (3 mg/kg) was administered. I n the titration group (n = 20), protamine doses were based on the heparin c oncentration measured by the Hepcon system. Results: Heparin concentrations before protamine administration mere higher in the titration group (P = .0 012), but protamine doses of patients in the titration group were markedly lower than those of the control group (P < .0001). During protamine infusio n at a rate of 0.3 mg.kg(-1).min(-1), the percentage of granule membrane pr otein-140-positive platelets significantly increased in the control group c ompared with the titration group (18.8% +/- 8.6% vs 13.0% +/- 5.3%, P = .01 88). After protamine administration, aggregation of washed platelets to thr ombin recovered almost to the preoperative level in the titration group; ho wever, it remained lower in the control group (20% +/- 20% vs 55% +/- 18%, P = .0009), Conclusion: Low-dose administration of protamine, based on a he parin-protamine titration method, restores not only the blood coagulation b ut also the platelet responses to thrombin and attenuates platelet agranule secretion during heparin neutralization. Overdose of protamine activates p latelets and may predispose patients to excessive bleeding after cardiac su rgery.