Platelet transfusions and mortality in necrotizing enterocolitis

Abstract

BACKGROUND Prior studies have suggested an association between platelet transfusions (PTXs) and worse outcomes among infants with necrotizing enterocolitis (NEC), potentially mediated by proinflammatory factors released by platelets. However, the effects of storage on platelet proinflammatory factor release and the confounding role of illness severity on NEC outcomes have not been determined. STUDY DESIGN AND METHODS First, neuropeptide Y (a potent splanchnic vasoconstrictor released by platelets) was measured by enzyme‐linked immunosorbent assay in fresh frozen plasma and in the supernatant of leukoreduced apheresis‐derived platelets at different times during storage. Next, we evaluated the relationship between PTX rates and death in a multicenter cohort of very‐low‐birth‐weight infants with NEC, adjusting for illness severity. RESULTS Neuropeptide Y levels increased over time in the supernatant of leukoreduced apheresis‐derived platelets and were 4.4‐fold and 8.9‐fold higher than in fresh frozen plasma on Days 2 and 3 of storage, respectively (p < 0.001). Among 598 very‐low‐birth‐weight infants, 44 developed NEC. In unadjusted analysis, PTX rate was 30.3 (95% confidence interval [CI], 11.5–80.1) per 100 infant‐days among infants who died, compared to 6.0 (95% CI, 3.2–11.2) among survivors (incidence rate ratio, 5.1; 95% CI, 1.6–16.2; p = 0.006). In multivariable analysis, there was no association between PTX rate and mortality (incidence rate ratio, 3.0; 95% CI, 0.6–15.0; p = 0.18), although estimation was imprecise. CONCLUSION Proinflammatory mediators accumulate in platelet suspensions during storage. Although PTX rates were not associated with increased mortality among infants with NEC in our study, our estimates suggest the potential for such an association that needs evaluation in larger studies.

Hemostatic Challenges in Neonates

“…While these findings might have seemed surprising at first, they were in fact consistent with a number of prior observational studies describing a poor association between severity of thrombocytopenia and bleeding risk (51, 53-55), a lack of effectiveness of platelet transfusions to prevent bleeding in neonates (51, 97), and an association between number of platelet transfusions and neonatal mortality and morbidity (98)(99)(100)(101).…”

Platelets in the neonate: Not just a small adult

“…This analysis demonstrated that neonates with the highest baseline risk of bleeding/mortality (based on accepted clinical factors such as gestational age, underlying diagnosis, etc) benefitted just as much as low‐risk neonates from the restrictive transfusion thresholds. While these findings seemed surprising at first, they were in fact consistent with several observational studies that had found a poor correlation between platelet count and bleeding risk (suggesting that factors other than platelet count are better predictors of bleeding risk in neonates), 7,11–14 no effect of platelet transfusions in reducing the incidence or severity of IVH, 8,12,15 and an association between number of platelet transfusions and increased neonatal morbidity and mortality 16–22 …”

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

“…Multiple observational studies have reported an association between severe anemia and the development of NEC [34][35][36]. Anemia can impair splanchnic perfusion and increase intestinal inflammation and barrier disruption leading to tissue hypoxia and anaerobic metabolism and thus predisposing to ischemic injury and possibly to NEC [37][38][39][40]. Thus, preventing anemia could be a strategy to prevent the development of NEC, and RBC transfusion is a commonly used method to achieve this [41,42].…”