Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding. Thromb Haemost 2020 Jan;120(1):94-106
Date
11/22/2019Pubmed ID
31752040Pubmed Central ID
PMC7003188DOI
10.1055/s-0039-1700517Scopus ID
2-s2.0-85077799720 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
Zwifelhofer NMJ, Bercovitz RS, Cole R, Yan K, Simpson PM, Moroi A, Newman PJ, Niebler RA, Scott JP, Stuth EAD, Woods RK, Benson DW, Newman DKAuthors
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinDebra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Robert Niebler MD Professor in the Pediatrics department at Medical College of Wisconsin
John P. Scott MD Professor in the Anesthesiology department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin
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
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidAdenosine Diphosphate
Blood Platelets
Cardiopulmonary Bypass
Cells, Cultured
Extracorporeal Circulation
Female
Heart Defects, Congenital
Humans
Infant, Newborn
Male
Platelet Activation
Platelet Count
Platelet Function Tests
Platelet Transfusion
Postoperative Hemorrhage
