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Heparin–protamine balance after neonatal cardiopulmonary bypass surgery
Author(s): ,
J. A. Peterson
Affiliations:
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, USA
,
S. A. Maroney
Affiliations:
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, USA
,
W. Zwifelhofer
Affiliations:
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, USA
,
J. P. Wood
Affiliations:
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, USA
,
K. Yan
Affiliations:
Departments of Pathology and Pediatrics, Medical College of Wisconsin, Milwaukee, USA
,
R. S. Bercovitz
Affiliations:
Departments of Pathology and Pediatrics, Medical College of Wisconsin, Milwaukee, USA
,
R. K. Woods
Affiliations:
HermaHeart Center, Division of Pediatric Cardiothoracic Surgery, Children's Hospital of Wisconsin, Milwaukee, USA. Department of Surgery, Medical College of Wisconsin, Milwaukee, USA
A. E. Mast
Affiliations:
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, USA. Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, USA
Correspondence: Alan E. Mast, Blood Research Institute, BloodCenter of Wisconsin, PO Box 2178, Milwaukee, WI 53201, USA|Tel.: +1 414 937 6310|E‐mail: alan.mast@bcw.edu
ISTH Academy. Mast A. Oct 4, 2018; 234164
Dr. Alan Mast
Dr. Alan Mast

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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.
Keyword(s)
cardiopulmonary, hemostasis, heparin, neonate, protamine
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