Heparin–protamine balance after neonatal cardiopulmonary bypass surgery

J. A. Peterson, S. A. Maroney, W. Zwifelhofer, J. P. Wood, K. Yan, Rachel Sara Bercovitz, R. K. Woods, A. E. Mast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1973-1983
Number of pages11
JournalJournal of Thrombosis and Haemostasis
Issue number10
StatePublished - Oct 2018


  • cardiopulmonary
  • hemostasis
  • heparin
  • neonate
  • protamine

ASJC Scopus subject areas

  • Hematology


Dive into the research topics of 'Heparin–protamine balance after neonatal cardiopulmonary bypass surgery'. Together they form a unique fingerprint.

Cite this