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 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.