Heparin–protamine balance after neonatal cardiopulmonary bypass surgery

• Published in: Journal of thrombosis and haemostasis 2018-10, Vol.16 (10), p.1973-1983
• Main Authors: Peterson, J. A., Maroney, S. A., Zwifelhofer, W., Wood, J. P., Yan, K., Bercovitz, R. S., Woods, R. K., Mast, A. E.
• Format: Article
• Language: English
• Subjects: Anticoagulants; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulants - blood; Bleeding; Blood coagulation; Blood Coagulation - drug effects; Blood Coagulation Tests; cardiopulmonary; Cardiopulmonary Bypass - adverse effects; Drug Monitoring - methods; Female; Fibrin; Heart; Heart surgery; hemostasis; Heparin; Heparin - administration & dosage; Heparin - adverse effects; Heparin - blood; Heparin Antagonists - administration & dosage; Heparin Antagonists - adverse effects; Heparin Antagonists - blood; Humans; Infant, Newborn; Male; neonate; Neonates; Postoperative Hemorrhage - blood; Postoperative Hemorrhage - diagnosis; Postoperative Hemorrhage - etiology; Predictive Value of Tests; Prospective Studies; protamine; Protamine sulfate; Protamines - administration & dosage; Protamines - adverse effects; Protamines - blood; Risk Factors; Tamponade; Thrombin; Thromboplastin; Treatment Outcome
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.14245

Essentials Heparin‐protamine balance (HPB) modulates bleeding after neonatal cardiopulmonary bypass (CPB). HPB was examined in 44 neonates undergoing CPB. Post‐operative bleeding occurred in 36% and heparin rebound in 73%. Thrombin‐initiated fibrin clot kinetic assay and partial thromboplastin time best assessed HPB. Summary Background Neonates undergoing cardiopulmonary bypass (CPB) are at risk of excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin. Objectives To evaluate heparin–protamine balance in neonates undergoing CPB by using research and clinical assays, and to determine its association with postoperative bleeding. Patients/Methods Neonates undergoing CPB in the first 30 days of life were studied. Blood samples were obtained during and after surgery. Heparin–protamine balance was assessed with calibrated automated thrombography, thrombin‐initiated fibrin clot kinetic assay (TFCK), activated partial thromboplastin time (APTT), anti‐FXa activity, and thromboelastometry. Excessive postoperative bleeding was determined by measurement of chest tube output or the development of cardiac tamponade. Results and Conclusions Of 44 neonates enrolled, 16 (36%) had excessive postoperative bleeding. The TFCK value was increased. By heparin in neonatal blood samples, but was only minimally altered by excess protamine. Therefore, it reliably measured heparin in samples containing a wide range of heparin and protamine concentrations. The APTT most closely correlated with TFCK results, whereas anti‐FXa and thromboelastometry assays were less correlative. The TFCK and APTT assay also consistently detected postoperative heparin rebound, providing an important continued role for these long‐established coagulation tests in the management of postoperative bleeding in neonates requiring cardiac surgical repair. None of the coagulation tests predicted the neonates who experienced postoperative bleeding, reflecting the multifactorial causes of bleeding in this population.