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

Katie R Forman, Yaser Diab, Edward C C Wong, Stephen Baumgart, Naomi L C Luban, An N Massaro, Katie R Forman, Yaser Diab, Edward C C Wong, Stephen Baumgart, Naomi L C Luban, An N Massaro

Abstract

Background: Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemic oxygen 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 abnormality that 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 thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleeding was defined as clinically significant if associated with 1) decreased hemoglobin (Hb) by 2 g/dL in 24 hours, 2) transfusion of blood products for hemostasis, or 3) involvement of a critical organ system. Laboratory data between the bleeding group (BG) and non-bleeding group (NBG) were compared. Variables that differed significantly between groups were evaluated with Receiver Operating Characteristic Curve (ROC) analyses to determine cut-points to predict bleeding.

Results: Laboratory and bleeding data were collected from a total of 76 HIE infants with a mean (±SD) birthweight of 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 differences between BG and NBG in baseline characteristics (p > 0.05). Both groups demonstrated INR and aPTT values beyond the 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, fib level <1.5 g/L, and INR >2 discriminated BG from NBG.

Conclusions: Laboratory evidence of coagulopathy is universal in HIE babies undergoing TH. Transfusion strategies to maintain PLT counts >130 × 109/L, fib level >1.5 g/L, and INR <2 may prevent clinical bleeding in this high risk population.

Figures

Figure 1
Figure 1
Each panel demonstrates a bar graph representing the mean ± SD for initial and max/min value of INR, aPTT, platelet count and fibrinogen level as labeled. The bleeding group is represented by dark bars and nonbleeding group is represented by light bars. The * indicates a p value of significance by Independent Samples T-test.
Figure 2
Figure 2
This figure shows the receiver operator curves used to determine cutpoints for the minimum platelet count, minimum fibrinogen level and maximum INR that predict clinical bleeding. AUC = Area under the receiver operator curve.

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