1. For preterm infants with echocardiographically-confirmed patent ductus arteriosus (PDA) within the first 14 days of life, there was no significant difference in the timing of PDA closure between infants who received liberal versus restrictive platelet transfusions.
2. Infants in the liberal transfusion group had significantly higher rates of intraventricular hemorrhage (IVH) of any grade compared to the restrictive group. There was no significant difference between groups for IVH grade III-IV. The cumulative volume of platelet transfusion was a significant risk factor in developing any grade IVH.
Evidence Rating: Level 1 (Excellent)
Study Rundown: Prospective data has supported a positive association between thrombocytopenia and PDA. One theory, based on animal studies, is that platelet accumulation within the PDA may lead to thrombus formulation and vascular remodeling, resulting in PDA closure. The purpose of this randomized controlled trial was to evaluate whether maintaining a platelet count of >100 000/uL in thrombocytopenic preterm infants with PDA identified in the first 14 days of life would result in the primary outcome of earlier PDA closure. Preterm infants with PDA were randomized into a “liberal” versus “restrictive” platelet transfusion group. Researchers found no statistically significant difference between groups for time to closure of the PDA. Significant secondary outcomes included higher volume of platelets transfused and higher rates of any grade IVH in the liberal group. However, there was no difference between groups for IVH grades III-IV. Follow-up analyses showed that cumulative volume of platelets received was a significant risk factor for any grade IVH. This study is limited by an inability to account for potential platelet dysfunction, which may explain why groups had similar outcomes. For neonatologists, these data suggest that liberal use of platelets in preterm infants with PDAs in the first 14 days of life will not increase time to closure and may increase risk of any grade of IVH.
Relevant Reading: Preterm thrombocytopenia and delay of ductus arteriosus closure
In-Depth [randomized controlled trial]: In this open-label trial at a level III NICU in Northwestern India, 44 infants were randomized to a “liberal” (n = 22) or “restrictive” (n = 22) platelet transfusion group. Inclusion criteria included inborn and outborn preterm (≤34 + 6/7 weeks’ gestational age) with a hs-PDA detected at <14 days postnatal age. All extremely low birth weight neonates had echocardiographic screening in the first 48 hours, and infants with clinically-suspected PDA underwent confirmatory echocardiogram. Exclusion criteria included structural congenital heart disease, life-threatening malformations, syndromes associated with PDA and platelet transfusion prior to randomization. In the “liberal” group, transfusion goals included maintaining platelets >100 000/uL until PDA closure or the 120h study period ended. In the restrictive group, platelet transfusion was indicated for platelets <20 000/uL, clinical bleeding, platelets <50 000/uL requiring nonneurosurgical interventional procedure, and platelets <100 000/uL requiring neurosurgery.
For the primary outcome, time between randomization and closure of the PDA, the median time for PDA closure in the liberal and restrictive groups were 72 (95%CI = 55.9-88.1) and 72 hours (95%CI = 45.5-98.4), respectively (unadjusted HR = 0.88, 95%CI = 0.4-1.9, p = 0.697). For secondary outcomes, there was a significant difference in the median cumulative volume of platelets received during the study period between the liberal (30mL/kg, first-third quartile = 15-55mL/kg) and restrictive group (10mL/kg, first-third quartile = 0-15mL/kg, P < 0.001). Any new-onset IVH during the study period was significantly higher in the liberal group (9 out 22, 40.9%) compared to the restrictive group (2 out of 22, 9.1%, P = 0.034). However, there was no significant difference between the liberal and restrictive groups in terms of new-onset IVH grade III-IV during the study period. In a follow-up multivariate logistic regression analysis, cumulative volume of platelets transfused in 120h was positive associated with any grade IVH (aOR = 1.045, 95%CI = 1.007-1.084, p = 0.019). There was no significant difference in the proportion of hs-PDA 120 hours after randomization, in the mortality rates during the study period, and in reopening of closed PDAs.
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