Although the transfusion of allogeneic red blood cells (RBCs) can correct anemia by raising hemoglobin levels, its clinical benefit has not been proven unequivocally. Some research points to ineffective and even harmful effects from liberal transfusions. These findings are of particular concern in neurocritical care patients, given that decreased oxygen delivery is an important cause of secondary brain injury. Specifically, patients with aneurysmal subarachnoid hemorrhage (SAH) commonly present with anemia, which has been identified as a predictor of death and infarction. There are no clinical data that show the benefit of aggressive transfusions in alleviating these risks, and some studies indicate that transfusion may exacerbate vasospasm and contribute to adverse respiratory effects. Kramer et al recently addressed these concerns in a study that assessed the association between anemia, transfusions, and adverse outcomes.

The retrospective cohort study included 245 patients with SAH who were admitted to a health care center over a 4-year period. The study examined hemoglobin (Hb) levels, the use of blood transfusions, development of vasospasm, and the relationship between anemia or transfusion and the combined outcome of death, severe disability, or delayed infarction. Optimal Hb concentrations were defined at 10 g/dL: 39% of patients developed Hb levels below this concentration at baseline; 35% of patients received transfusion; and 26% of patients were diagnosed with clinical vasospasm. The odds of reaching the primary outcome were higher in both anemic and transfused patients (OR 2.7 and 4.8 respectively) than in non-anemic and non-transfused patients. Transfusion remained the only significant variable associated with the combined outcome after multivariate analysis (OR 4.3). However, anemia had the stronger predictive association in patients with vasospasm whereas transfusion was the stronger predictor in those with no vasospasm. A strong association was observed between transfusion and the subsequent development of infection. The age of the transfused blood had no discernible impact, although the cutoff for storage duration was 21 days.

Although no previous studies have attempted to separate the effects of anemia from those of transfusion, the present study showed a strong association between transfusion and adverse effects. Transfusion can increase blood viscosity, cause vasoconstriction by depleting endothelial nitric oxide, and adversely affect RBC deformability and microvascular flow through blood storage. Despite these associations, the study’s results should only be considered hypothesis generating until further studies are conducted. The authors contend that one possible explanation for these associations is that physicians tend to transfuse patients who are “sicker,” which could introduce confounding variables that were not adjusted for in the study. Also, the presence or absence of vasospasm may be important for determining transfusion thresholds. Further studies, such as randomized trials of liberal versus restrictive transfusion, should be considered.

Kramer AH, Gurka MJ, Nathan B, Dumont AS, Kassell NF, Bleck TP. Complications associated with anemia and blood transfusion in patients with aneurysmal subarachnoid hemorrhage. Crit Care Med. 2008 Jul;36(7):2070-5.

NAAC Expert Commentary
Kramer et al’s study of the impact of anemia and transfusion in patients with ischemic brain injury from subarachnoid hemorrhage (SAH) is an important contribution to our understanding of not only which patients may or may not benefit from blood transfusion, but also of the relationship of anemia and transfusion to adverse outcomes. As the authors note, transfusion has long been thought to be required therapy in anemic, SAH patients to prevent cerebral ischemia. However, evidence to support this practice has not been forthcoming. This study’s evidence of a strong association between transfusion and adverse outcome in SAH should prompt all those who treat these patients to be more cautious with transfusion in the future.

Moreover, the study shows that anemia and transfusion are independent predictors of adverse outcome. This raises the question of how we should treat anemia in SAH patients. Will patients benefit from iron and erythropoietin treatment to raise hemoglobin levels while avoiding RBC transfusion? Will patients benefit from a non-hemoglobin based oxygen therapeutic to increase cerebral oxygen? Answers to these questions and to the question of the role of RBC transfusion in anemic SAH patients await study through prospective, randomized trials.

Last Updated: November 7, 2008