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Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding.

ABSTRACT: Thrombocytopenia and platelet dysfunction induced by extracorporeal blood circulation are thought to contribute to postsurgical bleeding complications in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this study, we examined how changes in platelet function relate to changes in platelet count and to excessive bleeding in neonatal CPB surgery. Platelet counts and platelet P-selectin exposure in response to agonist stimulation were measured at four times before, during, and after CPB surgery in neonates with normal versus excessive levels of postsurgical bleeding. Relative to baseline, platelet counts were reduced in patients while on CPB, as was platelet activation by the thromboxane A2 analog U46619, thrombin receptor activating peptide (TRAP), and collagen-related peptide (CRP). Platelet activation by adenosine diphosphate (ADP) was instead reduced after platelet transfusion. We provide evidence that thrombocytopenia is a likely contributor to CPB-associated defects in platelet responsiveness to U46619 and TRAP, CPB-induced collagen receptor downregulation likely contributes to defective platelet responsiveness to CRP, and platelet transfusion may contribute to defective platelet responses to ADP. Platelet transfusion restored to baseline levels platelet counts and responsiveness to all agonists except ADP but did not prevent excessive bleeding in all patients. We conclude that platelet count and function defects are characteristic of neonatal CPB surgery and that platelet transfusion corrects these defects. However, since CPB-associated coagulopathy is multifactorial, platelet transfusion alone is insufficient to treat bleeding events in all patients. Therefore, platelet transfusion must be combined with treatment of other factors that contribute to the coagulopathy to prevent excessive bleeding.

SUBMITTER: Zwifelhofer NMJ

PROVIDER: S-EPMC7003188 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding.

Zwifelhofer Nicole M J NMJ Bercovitz Rachel S RS Cole Regina R Yan Ke K Simpson Pippa M PM Moroi Alyssa A Newman Peter J PJ Niebler Robert A RA Scott John P JP Stuth Eckehard A D EAD Woods Ronald K RK Benson D Woodrow DW Newman Debra K DK

Thrombosis and haemostasis 20191121 1

Thrombocytopenia and platelet dysfunction induced by extracorporeal blood circulation are thought to contribute to postsurgical bleeding complications in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this study, we examined how changes in platelet function relate to changes in platelet count and to excessive bleeding in neonatal CPB surgery. Platelet counts and platelet P-selectin exposure in response to agonist stimulation were measured at four times before, during, ...[more]

PMID: 31752040

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Project description: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.SummaryBackground 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.

Dataset Information

Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding.

Publications

Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding.

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