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

Titreringsguidad protaminreversering efter hjärt-lungmaskin under kranskärlskirurgi kräver ingen skärpning för att förhindra blödningar postoperativt. Svenska och norska kirurger vid Linköping universitet och Oslo universitetsjukhus undersökte 40 patienter och fann att återstående heparinaktivitet var vanlig efter låg-dos protamintitration — 60 procent hade detekterbara nivåer vid ankomst till intensivvård. Tre timmar senare steg andelen till 98 procent, men denna återuppträdande aktivitet korrelerade inte med operationsblödning. Protamin-heparin-kvoten (0,54 mg/100 U) påverkade initiala koagulationsmarkörer (aPTT och TT) men inte den senare heparinökningen. Resultaten tyder på att automatiserad titreringsstyrd dosering säkert balanserar antikoagulation utan att öka blödningsrisk, vilket kan göra dyrare reverseringsprotokoll överflödiga och reducera postoperativa transfusionsbehov vid hjärtkirurgi.

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 was guided by an automated titration system. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained before induction, at the end of CPB, before and after protamine administration, on intensive care unit (ICU) arrival, 3 hours after ICU arrival, 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. On ICU arrival (82 ± 23 minutes after protamine), anti-FXa activity 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 activity 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 on ICU arrival. Reappearing heparin activity occurred independently of protamine dosing and was not associated with bleeding.