Estimation of Gestational Age-Specific Reference Intervals for Coagulation Assays in a Neonatal Intensive Care Unit Using Real-World Data.

Abstract

BACKGROUND Interpretation of coagulation testing in neonates currently relies on reference intervals (RIs) defined from older patient cohorts. Direct RI studies are difficult, but indirect estimation may allow us to infer normative neonatal distributions from routinely collected clinical data. METHODS We analyzed first-in-life coagulation testing results from all patients admitted to a level IV neonatal intensive care unit between 1/1/2018-1/1/2024. Results obtained after transfusion of any blood product were excluded. Indirect RIs were estimated across gestational age groups using refineR and compared to currently reported intervals for patients less than one year of age. RESULTS Prothrombin times (PT) and international normalized ratios (INR) were available for 1,128 neonates, while activated partial thromboplastin times (aPTT) were available for 790 neonates. The indirect RI was 10-25s in preterm, 10-22s in term, and 10-24s in all neonates for PT, 0.7-2.1 in preterm, 0.8-1.8 in term, and 0.8-1.9 in all neonates for INR, and 25-68s in preterm, 25-58s in term, and 25-62s in all neonates for aPTT. Compared to our current intervals, the indirect RIs would flag 58% fewer PT, 43% fewer INR, and 17% fewer aPTT results as abnormal. CONCLUSIONS Indirectly estimated RIs in neonates admitted to intensive care show substantial divergence from current, first-year-of-life RIs, leading to an abundance of abnormal flags. The associations between these flags and provider behavior, transfusion practice, or clinical outcomes is an area of future exploration.