In the field of neonatology, it is not uncommon to encounter clinical situations in which the risk/benefit of an intervention is unclear, usually as a result of insufficient or absent evidence to help guide clinical decision making. The patients we care for are among the most vulnerable and are at high risk for poor outcomes, and we know from history that our interventions can positively or negatively impact those outcomes. The field of neonatal transfusion medicine, specifically as it relates to platelet transfusions, has made significant progress since Dr Maureen Andrew published the first randomized trial of neonatal platelet transfusion thresholds 30 years ago. Due to the high incidence of both neonatal thrombocytopenia and bleeding (specifically intraventricular hemorrhage), platelet transfusions have historically been administered liberally to preterm neonates in hopes of decreasing bleeding and improving outcomes. Over the past 30 years, however, several studies showed that the platelet count is a poor predictor of bleeding, that liberal prophylactic platelet transfusions do not prevent bleeding, and that platelet transfusions may result in harm and worse outcomes. In 2019, the PlaNet-2 Trial was published, which was the largest randomized trial of neonatal platelet transfusion thresholds to date.1 This landmark study randomized premature infants to receive a platelet transfusion when the platelet count fell below 50 × 109/L (high threshold) or below 25 × 109/L (low threshold) and found increased mortality and major bleeding (the primary outcome) and an increased incidence of bronchopulmonary dysplasia (secondary outcome) in infants randomized to the high threshold. Recently, the 2-year follow-up from the PlaNet-2 Trial was published and found a higher rate of death or significant neurodevelopmental impairment and an increased need for supplemental oxygen at 2 years corrected age in infants randomized to the higher threshold.2 Together, this body of research from multiple investigators over the past three decades has highlighted the urgent need for practice change and also the need for a better understanding of the mechanisms underlying the harmful effects of neonatal platelet transfusions.
Platelets are the primary hemostatic cell in circulation, but over the last decade, it has become widely accepted that they are also active immune cells. Platelets contribute to both the innate and adaptive immune response in numerous ways, ranging from direct interactions with immune cells and bacteria to initiating complement activation and releasing their own immune mediators.3 Despite these advances in the field of platelet biology, however, frequently only the hemostatic functions of platelets are considered in clinical medicine and many providers are unaware of their immune functions. The immune activity of platelets might be especially important in neonatal intensive care since neonatal and adult platelets are functionally different, with neonatal platelets being hypo-reactive to common platelet agonists compared to adult platelets. How neonatal and adult platelets differ in regard to their immune functions and what role these differences play in the harm associated with neonatal platelet transfusions are active fields of research. A recent murine study found that the transfusion of adult, but not neonatal, platelets induced a migratory phenotype in neonatal monocytes.4 In septic neonatal mice, the transfusion of adult platelets impacted mortality and the systemic inflammatory response to infection in a context-dependent manner.5 Together, these studies suggest that the immune functions of platelets may play a role in the harm associated with neonatal platelet transfusion.
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