Platelet Transfusions for Thrombocytopenic Preterm Neonates: The Monet Study
Authors: Fustolo-Gunnink Suzanne F , Fijnvandraat K , Ree I M , Caram-Deelder C , Andriessen P , d'Haens E J , Hulzebos C V , Onland W , Kroon A A , Vijlbrief D C , Putter H , Lopriore E , van der Bom J G 
Published: April 2021

Abstract
Introduction
Limited evidence supports the widely used practice of administering platelet transfusions to prevent major bleeding in preterm thrombocytopenic neonates. Only 1 randomized controlled trial addressed this issue, but used thresholds higher than those currently used in clinical practice. In order to assess the impact of platelet transfusions on bleeding risk, the primary objective of this study was to develop a prediction model for bleeding. Platelet transfusion was included as variable in this model. In these secondary analyses, we further explored the impact of platelet transfusions on bleeding risk.
Materials and methods
In this multicenter cohort study, neonates with a gestational age (GA) &lt;34 weeks at birth, admitted to a neonatal intensive care unit (NICU) who developed a platelet count &lt;50x109/L were included. The main study endpoint was major bleeding, defined as intraventricular hemorrhage (IVH) grade 3, IVH with parenchymal involvement, other types of intracranial hemorrhage visible on ultrasound scans, pulmonary hemorrhage or any other type of bleeding requiring immediate interventions. The prediction model was developed using landmarking, in which multiple cox models at regular time-points were combined into 1 supermodel. To further explore the impact of platelet transfusions on bleeding risk, we performed 3 sensitivity analyses by selecting specific transfusions (instead of all transfusions). Sensitivity analysis 1 : transfusions according to protocol, defined as transfusions for platelet counts &gt;20x109/L only allowed in case of GA&lt;32 weeks and &lt;1500 grams and presence of NEC, sepsis, or treatment with mechanical ventilation, or in case of invasive procedures. Sensitivity analysis 2: transfusions with fair increments, defined as platelet count ≥50x109/L within 24 hours. Sensitivity analysis 3: transfusion dose 11 ml/kg or higher.
Results
A total of 640 neonates were included with a median gestational age of 28 weeks. 70 neonates developed a major bleed. IUGR, postnatal age, platelet count and mechanical ventilation were independent predictors of bleeding. The model allowed calculation of two bleeding risks for individual neonates: one in case of platelet transfusion and one in case of no platelet transfusion. 1361 platelet transfusions were administered to 449 of 640 (70%) neonates, of which 87 were hyperconcentrates. The hazard ratio for transfusion in the original model was 1.0, indicating no predictive power. Sensitivity analysis 1: 704 (52%) transfusions were given according to protocol. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.5, but the p-value remained &gt; 0.05.Sensitivity analysis 2: 764 (56%) of transfusions resulted in a count &gt;50x109/L within 24 hours. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.25, but the p-value remained &gt;0.05. 115 (8%) transfusions did not have a follow up platelet count within 24 hours. Sensitivity analysis 3: of the non-hyperconcentrated platelet transfusions, 517 of 1274 (41%) transfusions were ≥ 11 ml/kg. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.1, with a p-value of 0.05.
Conclusion
With this tool, absolute risk of bleeding in individual preterm thrombocytopenic neonates can be calculated. Additionally, risk of bleeding can be assessed for 2 scenarios: with and without platelet transfusion. This can help clinicians in deciding whether or not to transfuse a patient. In the primary model, platelet transfusion was not a predictor for bleeding risk. However, the findings of the sensitivity analyses suggest that transfusions with a dose &gt; 11ml/kg may have a more profound effect on bleeding risk.

Disclosures
No relevant conflicts of interest to declare.