Rao SV, Jollis JG, Harrington RA, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA. 2004;292:1555-62.
The increased use of invasive procedures and anticoagulant and fibrinolytic drugs in patients with ischemic heart disease in recent years predictably increases the potential for bleeding and perceived need for transfusion. Studies evaluating the association between transfusion and mortality have produced mixed results. A more pertinent clinical question is whether transfusion is beneficial or harmful in patients with acute coronary syndromes who acutely develop anemia during their hospitalization.
The authors used clinical data from three large international trials of patients with acute coronary syndromes (GUSTO IIb, PURSUIT, and PARAGON B) to determine the association between blood transfusion and outcomes among patients who developed moderate to severe bleeding, anemia, or both during their hospitalization.
Assessment of clinically significant bleeding complications was based on the GUSTO definition of severe (intracranial hemorrhage or hemodynamic compromise and requiring intervention) or moderate (hemodynamically stable but requiring blood transfusion) bleeding. The GUSTO IIb and PURSUIT trials used the above definition; PARAGON B categorized bleeding as “major or life threatening” (intracranial hemorrhage or bleeding leading to hemodynamic compromise requiring intervention) or “intermediate” (requiring transfusion or a decrease in hemoglobin of 5 g/dL or more, or a decrease in hematocrit ( 15%). Major or life-threatening bleeding episodes and intermediate bleeding episodes in PARAGON B were deemed equivalent to severe and moderate bleeding episodes in GUSTO.
Data were collected on the date, time, severity, and location of each bleeding event, and on the date and number of units of packed red blood cells and whole blood transfused. The primary end-point was 30-day all-cause mortality. Secondary end-points were occurrence of the composite of 30-day death or MI.
The unadjusted rates of 30-day death, MI, and composite death/MI were significantly higher among patients who received a transfusion (30-day death, 8.00% vs. 3.08%; p<.001; 30-day MI, 25.16% vs. 8.16%; p<.001; 30-day composite death/MI, 29.24% vs. 10.02%; p<.001).
After adjustment for baseline characteristics, bleeding and transfusion propensity, and nadir hematocrit, blood transfusion was associated with a hazard ratio for death of 3.94 (95% confidence interval, 3.26–4.75).
No significant association was found between transfusion and 30-day mortality at a nadir hematocrit of 25% or less (adjusted OR 1.13; 95% CI 0.70-1.82). However, at a nadir hematocrit higher than 25%, transfusion was associated with significantly higher odds of 30-day death, even after excluding patients who underwent CABG or those who died within the first 5 days of follow-up.
These findings differ from the findings of Wu et al. (1) who noted that blood transfusion was associated with lower 30-day mortality among elderly patients with MI if the admission hematocrit was 30% or lower. The current authors propose that their data is more robust due to meticulous collection through clinical trial records, and that their analysis accounts for timing of transfusion and indications for transfusion.
Many clinicians logically believe that augmentation of oxygen carrying capacity via transfusion would be beneficial to patients with active ischemia. However, the authors note that red blood cells in stored blood may be depleted of both 2,3-diphosphoglyceric acid and nitric oxide, both of which are critical components to oxygen delivery and exchange. These cells then function as nitric oxide “sinks,” promoting vasoconstriction, platelet aggregation, and impaired oxygen delivery to tissues. In addition, inflammatory mediators associated with exacerbation of myocardial ischemia may remain in transfused blood, potentially contributing to adverse outcomes.
As this is a nonrandomized, post hoc observational study, further prescriptive conclusions regarding transfusion cannot be made. However, the authors, along with an accompanying editorial, call for prospective randomized trials of transfusion in anemic patients with acute coronary syndromes to better define the role of this commonly used therapy. (CW)