Faculty Collaboration Database

Heparin-protamine balance after neonatal cardiopulmonary bypass surgery. J Thromb Haemost 2018 Oct;16(10):1973-1983

Date

07/18/2018

Pubmed ID

30016577

Pubmed Central ID

PMC6173634

DOI

10.1111/jth.14245

Scopus ID

2-s2.0-85052379121 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

UNLABELLED: 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.

Author List

Peterson JA, Maroney SA, Zwifelhofer W, Wood JP, Yan K, Bercovitz RS, Woods RK, Mast AE

Authors

Ronald K. Woods MD Professor in the Surgery department at Medical College of Wisconsin
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anticoagulants
Blood Coagulation
Blood Coagulation Tests
Cardiopulmonary Bypass
Drug Monitoring
Female
Heparin
Heparin Antagonists
Humans
Infant, Newborn
Male
Postoperative Hemorrhage
Predictive Value of Tests
Prospective Studies
Protamines
Risk Factors
Treatment Outcome