Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: A retrospective case-control study

Background: Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemicoxygen deprivation. Additionally, therapeutic hypothermia (TH) slows enzymatic activity of the coagulation cascade,leading to constitutive prolongation of routinely assessed coagulation studies. The level of laboratory abnormalitythat predicts bleeding is unclear, leading to varying transfusion therapy practices.Methods: HIE infants treated with TH between 2008-2012 were included in this retrospective study. Initial,minimum (min) and maximum (max) values of International Normalized Ratio (INR), activated partial thromboplastintime (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleedingwas defined as clinically significant if associated with 1) decreased hemoglobin (Hb) by 2 g/dL in 24 hours, 2) transfusionof blood products for hemostasis, or 3) involvement of a critical organ system. Laboratory data between thebleeding group (BG) and non-bleeding group (NBG) were compared. Variables that differed significantlybetween groups were evaluated with Receiver Operating Characteristic Curve (ROC) analyses to determinecut-points to predict bleeding.Results: Laboratory and bleeding data were collected from a total of 76 HIE infants with a mean (±SD) birthweightof 3.34 ± 0.67 kg and gestational age of 38.6 ± 1.9 wks. BG included 41 infants. Bleeding sites were intracranial(n = 13), gastrointestinal (n = 19), pulmonary (n = 18), hematuria (n = 11) or other (n = 1). There were no differencesbetween BG and NBG in baseline characteristics (p > 0.05). Both groups demonstrated INR and aPTT values beyondthe acceptable reference ranges utilized for full tem newborns. BG had higher initial and max INR, initial aPTT,and lower min PLT and min Fib compared to NBG. ROC analyses revealed that platelet count <130 × 10⁹/L, fiblevel <1.5 g/L, and INR >2 discriminated BG from NBG.Conclusions: Laboratory evidence of coagulopathy is universal in HIE babies undergoing TH. Transfusion strategiesto maintain PLT counts >130 × 10⁹/L, fib level >1.5 g/L, and INR <2 may prevent clinical bleeding in this highrisk population.