Anticoagulation management during pulmonary endarterectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest

Abstract

Introduction: Pulmonary endarterectomy requires cardiopulmonary bypass and deep hypothermic circulatory arrest, which may prolong the activated clotting time. We investigated whether activated clotting time–guided anticoagulation under these circumstances suppresses hemostatic activation. Methods: Individual heparin sensitivity was determined by the heparin dose–response test, and anticoagulation was monitored by the activated clotting time and heparin concentration. Perioperative hemostasis was evaluated by thromboelastometry, platelet aggregation, and several plasma coagulation markers. Results: Eighteen patients were included in this study. During cooling, tube-based activated clotting time increased from 719 (95% confidence interval = 566-872 seconds) to 1,273 (95% confidence interval = 1,136-1,410 seconds; p < 0.01) and the cartridge-based activated clotting time increased from 693 (95% confidence interval = 590-796 seconds) to 883 (95% confidence interval = 806-960 seconds; p < 0.01), while thrombin–antithrombin showed an eightfold increase. The heparin concentration showed a slightly declining trend during cardiopulmonary bypass. After protamine administration (protamine-to-heparin bolus ratio of 0.82 (0.71-0.90)), more than half of the patients showed an intrinsically activated coagulation test and intrinsically activated coagulation test without heparin effect clotting time >240 seconds. Platelet aggregation through activation of the P2Y12 (adenosine diphosphate test) and thrombin receptor (thrombin receptor activating peptide-6 test) decreased (both −33%) and PF4 levels almost doubled (from 48 (95% confidence interval = 42-53 ng/mL) to 77 (95% confidence interval = 71-82 ng/mL); p < 0.01) between weaning from cardiopulmonary bypass and 3 minutes after protamine administration. Conclusion: This study shows a wide variation in individual heparin sensitivity in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest. Although activated clotting time–guided anticoagulation management may underestimate the level of anticoagulation and consequently result in a less profound inhibition of hemostatic activation, this study lacked power to detect adverse outcomes.