van der Staaij Hilde, Prosepe Ilaria, Caram-Deelder Camila, Keogh Ruth H, Deschmann Emöke, Dame Christof, Onland Wes, Prins Sandra A, Cassel Florian, d'Haens Esther J, van Westering-Kroon Elke, Andriessen Peter, Vrancken Sabine L, Hulzebos Christian V, Vijlbrief Daniel C, Fustolo-Gunnink Suzanne F, Fijnvandraat Karin, Lopriore Enrico, van der Bom Johanna G, van Geloven Nan
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Pediatrics, Division of Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands.
JAMA. 2025 Sep 15. doi: 10.1001/jama.2025.14194.
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.
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.
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).
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.
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.
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.
患有严重血小板减少症（血小板计数<50×10⁹/L）的早产儿经常接受血小板输注。然而，尚不清楚在哪些情况下预防性输血真的能降低出血风险，或者它是否弊大于利。
建立并验证一个动态预测模型，用于预测患有严重血小板减少症的婴儿接受或不接受预防性血小板输注时发生大出血或死亡的情况。
设计、地点和参与者：动态预测模型是在一个国际多中心队列（2017 - 2021年）中开发的，该队列包括荷兰、瑞典和德国的14个新生儿重症监护病房。模型评估在一个全国多中心队列（2010 - 2014年）中进行，该队列包括7个荷兰新生儿重症监护病房。研究人群包括孕周小于34周的严重血小板减少症婴儿。
在每个预测点对比两种输血策略：在6小时内接受血小板输注（预防）与3天不接受血小板输注（不预防）。
主要结局是严重血小板减少症发作后第一周内每2小时重新估计一次的3天大出血或死亡风险。预测因素包括孕周和出生后年龄、小于胎龄儿、坏死性小肠结肠炎、败血症、机械通气、血管活性药物、血小板计数和既往血小板输注情况。地标法结合克隆审查权重方法能够在两种输血策略下进行动态预测，同时考虑随时间变化的混杂因素。在外部验证队列中评估模型性能。
在开发队列（n = 1042）和验证队列（n = 637）中，中位孕周均为28周，中位出生体重均为900 g；男性分别有613例（59%）和370例（58%）。开发队列中有235例婴儿（23%）发生大出血或死亡，验证队列中有135例（21%）。在验证队列中，预防策略的受试者工作特征曲线下的时间依赖性面积为0.69（95%CI，0.60 - 0.76），不预防策略为0.85（95%CI，0.76 - 0.92），校准图显示校准良好。根据预测时婴儿的临床状况，两种策略下估计的风险有很大差异。
在患有严重血小板减少症的早产儿中，这项建模研究发现，根据个体当前的临床特征，预防性血小板输注的预测益处和危害存在很大差异。动态预测模型在验证队列中表现良好，其支持个体化决策的价值值得在未来研究中进行评估。
