JAMA. 2025 Sep 15. doi: 10.1001/jama.2025.14194. Online ahead of print.
ABSTRACT
IMPORTANCE: Preterm infants with severe thrombocytopenia (platelet count <50 × 109/L) frequently receive platelet transfusions. However, it is unclear in what cases prophylactic transfusion truly reduces bleeding risk or whether it does more harm than good.
OBJECTIVE: To develop and validate a dynamic prediction model for major bleeding or mortality if prophylactic platelet transfusion were or were not to be given to infants with severe thrombocytopenia.
DESIGN, SETTING, AND PARTICIPANTS: The dynamic prediction model was developed in an international multicenter cohort (2017-2021) comprising 14 neonatal intensive care units in the Netherlands, Sweden, and Germany. Model evaluation was performed in a national multicenter cohort (2010-2014) including 7 Dutch neonatal intensive care units. The study population consisted of infants with severe thrombocytopenia less than 34 weeks’ gestation.
EXPOSURE: Two transfusion strategies were contrasted at each prediction point: receiving a platelet transfusion within 6 hours (prophylaxis) vs no platelet transfusion for 3 days (no prophylaxis).
MAIN OUTCOMES AND MEASURES: The primary outcome was the 3-day risk of major bleeding or mortality, reestimated every 2 hours during the first week after severe thrombocytopenia onset. Predictors included gestational and postnatal age, small-for-gestational-age infant, necrotizing enterocolitis, sepsis, mechanical ventilation, vasoactive agents, platelet count, and prior platelet transfusion(s). Landmarking combined with the clone-censor-weight approach enabled dynamic prediction under the 2 transfusion strategies, accounting for time-varying confounding. Model performance was evaluated in the external validation cohort.
RESULTS: In both the development (n = 1042) and validation (n = 637) cohorts, the median gestational age was 28 weeks and median birth weight was 900 g; there were 613 (59%) and 370 (58%) males, respectively. Major bleeding or death occurred in 235 infants (23%) in the development cohort and 135 (21%) in the validation cohort. In the validation cohort, the time-dependent area under the receiver operating characteristic curve was 0.69 (95% CI, 0.60-0.76) for the prophylaxis strategy and 0.85 (95% CI, 0.76-0.92) for the no prophylaxis strategy, with calibration plots showing good calibration. Estimated risks under both strategies varied considerably depending on the infant’s clinical condition at the time of prediction.
CONCLUSIONS AND RELEVANCE: Among preterm infants with severe thrombocytopenia, this modeling study found substantial variation among individuals in predicted benefits and harms of prophylactic platelet transfusion based on their current clinical characteristics. The dynamic prediction model performed well in a validation cohort, and its value to support individualized decisions warrants evaluation in future studies.
PMID:40952748 | DOI:10.1001/jama.2025.14194
