Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study

Abstract

BackgroundBleeding complications are common in cardiac surgery. Perioperative handling of heparin and protamine may influence the haemostasis. We hypothesized that heparin and protamine dosing based on individual titration curves would improve haemostasis in comparison to standard dosing.Subjects and MethodsSixty patients scheduled for first time elective coronary artery bypass grafting or valve surgery were included in a prospective randomized study. The patients were randomized to heparin and protamine dosing with Hepcon HMS Plus device or to standard weight and activated clotting time (ACT) based dosing. Blood samples were collected before and 10 minutes, 2 hours and 4 hours after cardiopulmonary bypass. Primary endpoint was endogenous thrombin potential in plasma 2 hours after surgery as assessed by calibrated automated thrombography. Secondary endpoints included total heparin and protamine doses, whole blood clot formation (thromboelastometry) and post-operative bleeding volume and transfusions. Heparin effect was assessed by measuring anti-Xa activity.ResultsEndogenous thrombin potential and clot formation deteriorated in both groups after surgery without statistically significant intergroup difference. There were no significant differences between the groups in total heparin and protamine doses, heparin effect, or postoperative bleeding and transfusions at any time point. Significant inverse correlations between anti-Xa activity and endogenous thrombin potential were observed 10 min (r = -0.43, p = 0.001), 2 hours (r = -0.66, p<0.001) and 4 hours after surgery (r = -0.58, p<0.001).ConclusionIn conclusion, the results suggest that perioperative heparin and protamine dosing based on individual titration curves does not improve haemostasis after cardiac surgery. Postoperative thrombin generation capacity correlates to residual heparin effect.Trial Registration www.isrctn.com ISRCTN14201041.

2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery

“…167 A Hepconbased anticoagulation strategy did not influence heparin and protamine dosing or postoperative haemostasis or bleeding compared to ACT-based dosing. 168 Contrarily, the use of the Hepcon/HMS device resulted in a highly significant difference for the total protamine dose compared to ACT-based dosing (mean protamine dose: 14.190 IU vs 24.777 IU; P < 0.001) and total blood volume (mean blood loss: 804 ml vs 1416 ml; P < 0.001), whereas there was no difference in the total heparin dose. 169 Due to the lack of perioperative bleeding and transfusion rates as primary end points in these studies, larger multicentre studies are required to determine the added value of individual heparin management in the modern cardiosurgical setting.…”

Managing the coagulopathy associated with cardiopulmonary bypass

“…53 Heparin management systems may reduce the total dose of protamine, blood loss, and transfusion, although study results have been mixed. [53][54][55][56][57] Heparin resistance occurs when a patient requires much higher than anticipated dosing to achieve an acceptable ACT pre-CPB, and can be defined as an inability to achieve a therapeutic ACT with > 600 IU/kg of heparin. 58 Heparin resistance may be due to high plasma fibrinogen, thrombocytosis, or congenital or acquired antithrombin deficiency.…”

2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery

“…150,151,153,[158][159][160] In contrast, others did not show favourable results for blood loss and transfusion requirements when heparin titration was compared with an ACT-based protocol. 152,[161][162][163] Due to the lack of perioperative bleeding and transfusion rates as primary end points in these studies, larger multicentre RCTs are required to determine the added value of individual heparin management. Alternative methods of heparin management and anticoagulation monitoring during ECC consist of the determination of anti-factor Xa activity.…”