Transfusion Therapy in Aneurysmal Subarachnoid Hemorrhage
March 1, 2025
By Santosh Murthy, MD
Synopsis: The SAHARA trial evaluated liberal vs. restrictive red blood cell transfusion strategies in aneurysmal subarachnoid hemorrhage (SAH) patients with anemia. No significant difference in neurological outcomes at 12 months was found. Findings add to existing uncertainty regarding transfusion thresholds in SAH, highlighting the need for further research.
Source: English SW, Delaney A, Fergusson DA, et al. Liberal or restrictive transfusion strategy in aneurysmal subarachnoid hemorrhage. N Engl J Med. 2024; Dec 9. doi: 10.1056/NEJMoa2410962. [Online ahead of print].
Aneurysmal subarachnoid hemorrhage (SAH) has a high case-fatality rate, particularly in the acute period. An important complication that occurs in about 46% of patients with SAH is symptomatic cerebral vasospasm, which most likely is an inflammatory reaction in the blood vessel wall and usually develops between days 4 and 12 after SAH onset. Cerebral vasospasm, in turn, leads to cerebral ischemia and infarction. Low hemoglobin levels can adversely affect the oxygen-carrying capacity of blood and potentially exacerbate cerebral ischemia in SAH patients with vasospasm. In fact, anemia, which occurs in nearly half of SAH patients, is associated with poor long-term outcomes. However, it is unclear if blood transfusion can improve outcomes in SAH patients with anemia, or what the permissible hemoglobin thresholds should be.
In this context, the authors performed the Subarachnoid Hemorrhage Red Cell Transfusion Strategies and Outcome (SAHARA) trial to test the hypothesis that a liberal red blood cell (RBC) transfusion strategy, as compared with a restrictive RBC strategy, improves neurologic outcomes at 12 months. Adult patients (18 years of age or older) with a first-ever aneurysmal SAH and a hemoglobin level of 10 g/dL or lower recorded within the first 10 days after admission were eligible for inclusion in the trial. The interventions included a liberal strategy where RBC transfusions were mandatorily administered at a hemoglobin level of ≤ 10 g/dL or a restrictive strategy where RBC transfusions were optional at a hemoglobin level of ≤ 8 g/dL. The primary outcome was an unfavorable neurologic outcome, defined as a score of 4 or higher on the modified Rankin Scale at 12 months.
Secondary outcomes included 12-month functional independence and quality of life, assessed using several validated indices. A total of 732 SAH patients were enrolled in the trial, of whom 366 were randomized to the liberal strategy, while the other half were randomized to the restrictive strategy arm. There was no association between the interventions and unfavorable neurological outcome (risk ratio, 0.88; 95% confidence interval, 0.72-1.09). Similarly, there was no significant relationship between the transfusion strategy and functional independence or quality of life at 12 months. Important limitations of the trial were the absence of blinding of the study intervention (RBC transfusion) and lack of ascertainment of vasospasm and cerebral infarction, which are important prognostic markers in SAH.
Commentary
The topic of RBC transfusion in critically ill patients has been controversial, with prior trials reporting conflicting results. One of the first and landmark trials was the TRICC (Transfusion Requirements in Critical Care) trial, where a restrictive transfusion strategy was associated with lower in-hospital mortality, compared to a liberal transfusion strategy. However, the lack of inclusion of primary neurologic critically ill patients limited the generalizability of these results.
In recent times, two other trials have explored RBC transfusion thresholds in neurologic critically ill patients. First, in the HEMOTION (Hemoglobin Transfusion Threshold in Traumatic Brain Injury Optimization) trial, a liberal transfusion strategy (for a hemoglobin level ≤ 10 g/dL) did not reduce the risk of an unfavorable neurologic outcome at six months compared to a restrictive strategy of initiating transfusions only for hemoglobin ≤ 7 g/dL. In the TRAIN (Transfusion Strategies in Acute Brain Injured Patients) trial, patients randomized to receiving transfusions for a hemoglobin goal of < 9 g/dL (liberal strategy) had a 14% reduction in the risk of an unfavorable neurologic outcome, compared to those who had a transfusion goal of < 7 g/dL (restrictive strategy). Notably, about 23% of the enrolled patients had an SAH.
In the context of these findings, results from the SAHARA trial add to the equipoise about the role of RBC transfusions for anemia in SAH. Future individual patient-level meta-analyses combining the SAHARA and TRAIN trials may yield more valuable information on the safety and efficacy of transfusion strategies for SAH patients with anemia.
Santosh Murthy, MD, is Assistant Professor of Neurology, Weill Cornell Medical College.
The SAHARA trial evaluated liberal vs. restrictive red blood cell transfusion strategies in aneurysmal subarachnoid hemorrhage (SAH) patients with anemia. No significant difference in neurological outcomes at 12 months was found. Findings add to existing uncertainty regarding transfusion thresholds in SAH, highlighting the need for further research.
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