Platelet transfusions at higher threshold associated with greater risk of death in preterm infants

1. Preterm infants given prophylactic platelet transfusions at thresholds below 50,000 platelets per cubic millimeter had higher risks of death or major bleeding after 28 days as compared to neonates given transfusions at thresholds below 25,000 per cubic millimeter.

2. There was no significant difference in other serious adverse events between groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Preterm infants with thrombocytopenia are often given prophylactic platelet transfusions to reduce their risk of bleeding. However, guidelines for when to prophylactically begin platelet transfusions in preterm neonates with thrombocytopenia are currently lacking. In this randomized control trial, investigators studied the comparative effects of initiating platelet transfusions at platelet thresholds of 50,000 per cubic millimeter (high-threshold) versus 25,000 per cubic millimeter (low-threshold). The primary outcome was death or new major bleeding event within 28 days after randomization. Neonates randomized to receive platelet transfusions at below the higher-threshold had significantly higher death and major bleeding rates.

These findings may aid in creating objective threshold guidelines for platelet transfusions among neonates with thrombocytopenia. Limitations of the study include a minority of patients recruited during the first 5 days of life and possibly reduced generalizability as very few eligible patients were ultimately enrolled in the study.

Click to read the study in NEJM

Click to read an accompanying editorial in NEJM

Relevant Reading: Prospective, observational study of outcomes in neonates with severe thrombocytopenia

In-Depth [randomized controlled trial]: This multicenter randomized control trial enrolled a total of 660 premature infants to either receive platelet transfusions at thresholds below 25,000 platelets per cubic millimeter (low-threshold; n=331) or below 50,000 platelets per cubic millimeter (high-threshold; n=329). The median birth weight was 740 grams and median gestational age at enrollment was 26.6 weeks. The primary outcome was the composite risk of death or major bleeding up to 28 days after randomization. Secondary outcomes included but were not limited to: survival rates up to day 28 after randomization, the rate and time of any noted major bleeding, evidence of moderate or minor bleeding, chronic lung disease, stage 2 retinopathy up to 28 weeks gestational age, evidence of retinopathy of prematurity or bevacizumab treatment up to 38 weeks gestational age. There was a higher risk of bleeding events or death after 28 days noted among the high-threshold group as compared to the low-threshold group (26% vs 19%; odds ratio [OR], 1.57; 95% confidence interval [CI], 1.06 to 2.32; P=0.02).  A higher percentage of neonates in the high-threshold group (90%) received at least one platelet transfusion compared to the low-threshold group (53%). There were no significant differences between groups when rates of minor bleeding were compared. The death rate in the high-threshold group was 15% (48 infants) compared to 10% (33 infants) in the low-threshold group (OR, 1.56; 95% CI, 0.95 to 2.55). Other serious adverse events were also noted, including multiorgan failure necrotizing enterocolitis, renal failure, respiratory failure and sepsis. There were no significant differences in the rate of these adverse events between groups (25% high threshold versus 22% low threshold; OR, 1.14; 95% CI, 0.78 to 1.67).

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