2021 IARS Mentored Research Award
Laura Downey, MD
Dr. Downey’s Research
Characterizing platelet function in neonates undergoing cardiac surgery
Neonates undergoing cardiac surgery are at risk for bleeding and multiple transfusions due to the effects of cardiopulmonary bypass (CPB), hemodilution, and an immature coagulation system that contribute to platelet deficiency and impaired platelet function. While many platelet function tests allow clinicians to guide hemostatic therapy in adult cardiac surgery, these tests were designed for adults and report conflicting data in neonates. Our novel quantitative test of platelet function, platelet contraction cytometry (PCC), has shown that single platelet forces correlate strongly with bleeding in pediatric patients. In this study, we will utilize PCC to measure individual platelet contraction force as a biomarker for neonatal platelet function. We postulate this technology can be used to stratify bleeding risk during cardiac surgery and provide real time information to guide transfusion targets in efforts to minimize unnecessary transfusions.
For this study, we will use thromboelastography, platelet aggregometry, and PCC to compare differences in platelet function between healthy adults and neonates. For the second part of the study, we will evaluate the effect of CPB on neonatal platelet function. We will collect blood samples from 15 neonates undergoing non-emergent cardiac surgery at 3 times: 1) baseline; 2) post-CPB before transfusion; 3) post-CPB after platelet transfusion. Using PCC, we will characterize changes in platelet contraction force post-CPB and after transfusion, and explore neonatal platelet contraction force in the presence of either adult fibrinogen or neonatal fibrinogen to understand the effect of adult blood transfusions on neonatal hemostasis. Finally, we will conduct mechanistic studies to explore etiologies for platelet exhaustion in neonates post-CPB. The results of this study will allow us to understand important differences between adult and neonatal platelets and elucidate important platelet interactions after CPB or transfusions.