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 50×10(9)/L. INTERVENTIONS Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×10(9)/L (higher threshold group) or 25×10(9)/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 50×10(9)/L compared with 25×10(9)/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 ISRCTN87736839.

Abstract

The Platelets for Neonatal Thrombocytopenia (PlaNeT-2) trial reported an unexpected overall benefit of a prophylactic platelet transfusion threshold of 25x109/L compared to 50x109/L for major bleeding and/or mortality in preterm neonates (7% absolute risk reduction). However, some neonates in the trial may have experienced little benefit or even harm from the 25x109/L threshold. We aimed to assess this heterogeneity of treatment effect in the PlaNet-2 trial, in order to investigate whether all preterm neonates benefit from the low threshold. We developed a multivariable logistic regression model in the PlaNet-2 data to predict baseline risk of major bleeding and/or mortality for all 653 neonates. We then ranked the neonates based on their predicted baseline risk and categorized them into four risk quartiles. Within these quartiles we assessed absolute risk difference between the 50x109/L and 25x109/L threshold group. A total of 146 neonates died or developed major bleeding. The internally validated C-statistic of the model was 0.63 (95% confidence interval 0.58 - 0.68). The 25x109/L threshold was associated with absolute risk reduction in all risk groups, varying from 4.9% in the lowest to 12.3% in the highest risk group. These results suggest that a 25x109/L prophylactic platelet count threshold can be adopted in all preterm neonates, irrespective of predicted baseline outcome risk. Future studies are needed to improve the predictive accuracy of the baseline risk model. Current Controlled Trials number ISRCTN87736839.

Abstract

BACKGROUND Platelet transfusions are commonly used to prevent bleeding in preterm infants with thrombocytopenia. Data are lacking to provide guidance regarding thresholds for prophylactic platelet transfusions in preterm neonates with severe thrombocytopenia. METHODS In this multicenter trial, we randomly assigned infants born at less than 34 weeks of gestation in whom severe thrombocytopenia developed to receive a platelet transfusion at platelet-count thresholds of 50,000 per cubic millimeter (high-threshold group) or 25,000 per cubic millimeter (low-threshold group). Bleeding was documented prospectively with the use of a validated bleeding-assessment tool. The primary outcome was death or new major bleeding within 28 days after randomization. RESULTS A total of 660 infants (median birth weight, 740 g; and median gestational age, 26.6 weeks) underwent randomization. In the high-threshold group, 90% of the infants (296 of 328 infants) received at least one platelet transfusion, as compared with 53% (177 of 331 infants) in the low-threshold group. A new major bleeding episode or death occurred in 26% of the infants (85 of 324) in the high-threshold group and in 19% (61 of 329) in the low-threshold group (odds ratio, 1.57; 95% confidence interval [CI], 1.06 to 2.32; P=0.02). There was no significant difference between the groups with respect to rates of serious adverse events (25% in the high-threshold group and 22% in the low-threshold group; odds ratio, 1.14; 95% CI, 0.78 to 1.67). CONCLUSIONS Among preterm infants with severe thrombocytopenia, those randomly assigned to receive platelet transfusions at a platelet-count threshold of less than 50,000 per cubic millimeter had a significantly higher rate of death or major bleeding within 28 days after randomization than those in the group that received less than 25,000 per cubic millimeter. (Funded by the National Health Service Blood and Transplant Research and Development Committee and others; Current Controlled Trials number, ISRCTN87736839 .).