Restrictive Versus A Liberal Transfusion Strategy in Patients With Spontaneous Intracerebral Hemorrhage: A Secondary Analysis of TRAIN Randomized Clinical Trial

Stroke. 2025 Jun 17. doi: 10.1161/STROKEAHA.125.050729. Online ahead of print.

Abstract

Background: Red blood cell transfusions are commonly administered to anemic patients with spontaneous intracerebral hemorrhage (ICH); however, the optimal hemoglobin threshold to initiate transfusion is uncertain in this population. Therefore, we aimed to assess the impact of 2 different hemoglobin thresholds to guide transfusion on the neurological outcome of anemic critically ill patients with ICH.

Methods: This is a secondary analysis of a prospective, multicenter, phase 3 randomized study conducted in 72 intensive care units across 22 countries from 2017 to 2022. Eligible patients for the original trial had an acute brain injury, hemoglobin values ≤9 g/dL within the first 10 days after admission, and an expected intensive care unit stay of at least 72 hours; in this study, only patients with spontaneous ICH were assessed. Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤7 g/dL) or a liberal (transfusion triggered by hemoglobin ≤9 g/dL) strategy over a 28-day period. The primary outcome was the occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5, at 180 days following randomization.

Results: A total of 144 patients with spontaneous ICH were analyzed: 45.8% of them were male, with a mean age of 58.4 (SD, 13.4). Mean Glasgow Coma Scale on admission was 7.3 (SD, 3.3), and 75.7% of patients had a volume of hematoma >30 mL. Among all patients, 73 were randomized to the restrictive transfusion strategy, while 71 to the liberal one. Baseline characteristics were comparable between the 2 groups. At 180 days after randomization, patients assigned to the liberal transfusion strategy had a nonsignificant decrease in the probability of unfavorable neurological outcome (71.8 versus 84.7%; risk ratio, 0.85 [95% CI, 0.71-1.01]; P=0.06). Also, the occurrence of the composite outcome (mortality and organ failure at day 28) was significantly lower in the liberal group (71.8% versus 87.7%, risk ratio, 0.82 [95% CI, 0.69-0.97]; P=0.02).

Conclusions: A liberal transfusion strategy was associated with a lower risk of mortality and organ failure, but not of unfavorable outcome in patients presenting with spontaneous ICH, compared with a restrictive strategy. However, the study cohort might have been underpowered to detect clinically relevant differences between the 2 interventions.

Keywords: critical illness; hemoglobins; humans; odds ratio; random allocation.