Two-year outcomes following a randomised platelet transfusion trial in preterm infants

Abstract

Objective Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. Design Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. Setting 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. Patients 660 infants born at less than 34 weeks’ gestation with platelet counts less than 50×109/L. Interventions Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). Main outcomes measures Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. Results Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). Conclusions Infants randomised to a higher platelet transfusion threshold of 50×109/L compared with 25×109/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. Trial registration number NCT87736839.

Platelet Transfusion and Death or Neurodevelopmental Impairment in Children Born Extremely Preterm

“…Platelet transfusion may also be associated with a higher risk of moderate to severe NDI in these children, and with lower motor scores on the BSID-III. These findings are consistent with the recently published 2-year outcomes from the PlaNet-2 Trial, which found a rate of death or significant NDI at a corrected age of 2 years of 50% in infants randomized to the higher platelet transfusion threshold of 50 × 10 3 /μL compared with 39% in infants randomized to the lower threshold of 25 × 10 3 /μL (OR, 1.54; 95% CI, 1.09-2.17; P = .02) . In the PlaNet-2 Trial, 90% of infants in the high threshold group and 53% of infants in the low threshold group received at least 1 platelet transfusion.…”

“…In analysis of the primary outcome, the study found a higher incidence of death and/or major bleeding in infants randomized to the high compared with the low platelet transfusion threshold arm. A 2-year neurodevelopmental follow-up from this trial was recently published . Follow-up data were available for 601 (92%) of eligible participants, with 50% of children previously randomized to the high threshold group experiencing death or survival with unfavorable neurodevelopmental outcome, compared with 39% in the low threshold group (odds ratio [OR], 1.54; 95% CI, 1.09-2.17; P = .02).…”

Phosphoproteomics reveals content and signaling differences between neonatal and adult platelets

“…Several studies have shown that PDGF strongly contributes to airway remodeling in asthma, both by inducing the migration and proliferation of airway smooth muscle cells and by increasing the synthesis of collagen by fibroblasts [62]. Increased PDGF subunits in adult platelets could help explain the higher incidence of bronchopulmonary dysplasia (BPD) among preterm infants exposed to more platelet transfusions, since this is a disease process also characterized by airway obstruction and lung fibrosis [32, 63].…”

Platelet Transfusions in Neonates: Beyond Hemostasis

“…Recently, a significantly higher rate of death or neurodevelopmental impairment at 2 years of age was reported among children previously randomized to the higher platelet transfusion threshold in the PlaNeT-2 study compared to those randomized to the lower threshold, raising the possibility that platelet transfusions might also affect the developing brain through unknown mechanisms. 15 While many questions remain unanswered, the study by Maurya et al 9 Ly6C hi (proinflammatory) monocytes increased significantly in response to adult as well as neonatal platelet transfusions. However, pups transfused with adult platelets exhibited significantly increased platelet-monocyte aggregates and trafficking monocytes (typified by increased CCR2 and CCR5 surface expression), compared to pups transfused with neonatal platelets.…”