Heparin Activity Following Titration-Guided Protamine Reversal After Cardiopulmonary Bypass: Impact on Postoperative Bleeding

Objectives : To evaluate postoperative residual and reappearing heparin activity after low-dose, titration-guided protamine reversal following cardiopulmonary bypass (CPB) in elective coronary artery bypass grafting (CABG). Design : Prospective, controlled clinical study. Setting : Single center university hospital. Participants : Forty adult patients undergoing elective CABG with CPB. Interventions : Heparin and protamine dosing were guided by an automated titration system. Measurements and Main Results : Blood samples were obtained before induction, at CPB end, before and after protamine, at ICU arrival, 3 hours later, and on postoperative day 1. Heparin activity was assessed by anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT), and thrombin time (TT). Global coagulation was evaluated using endogenous thrombin potential (ETP). The mean protamine-to-heparin (P/H) ratio was 0.54 ± 0.14 mg/100 U. At ICU arrival (82 ± 23 minutes after protamine), anti-FXa was 0.14 ± 0.15 U/mL, with 60% of patients showing detectable levels. The P/H ratio correlated negatively with TT (r = –0.48, p = 0.004) and aPTT (r = –0.50, p = 0.0015), and positively with ETP (r = 0.41, p = 0.0012). Three hours after ICU arrival, anti-FXa increased to 0.18 ± 0.10 U/mL (98% detectable), independent of P/H ratio. No association was found between heparin activity and postoperative bleeding. Conclusions : Residual heparin activity was common after low-dose, titration-guided protamine reversal and related to P/H ratio at ICU arrival. Reappearing heparin activity occurred independently of protamine dosing, without association to bleeding.