Anemia vs Transfusion: The Chicken or the Egg

INVITED COMMENTARY:

Historically, anemia in cardiovascular surgery has been associated with worse morbidity and mortality, resulting in blood product overuse.¹ Conversely, recent literature suggests that each unit of blood transfusion may result in worse clinical outcomes and increased postoperative complications.² Such evolving perspective has led to inconsistent transfusion guidelines, yielding discretion by many surgeons. This development leads us to question which causes harm first, the anemia or the transfusion?

In this issue of The Annals of Thoracic Surgery, Hosseini and colleagues³ explore the association between preoperative anemia and intraoperative red blood cell (RBC) transfusion on outcomes of coronary artery bypass surgery (CABG). Their study comprised a retrospective analysis of 53,856 adult patients who underwent elective isolated CABG in The Society of Thoracic Surgeons Adult Cardiac Database in 2019. Using multivariable and binary regression models, they evaluated the impacts of preoperative anemia and intraoperative transfusion on various outcomes, including 30-day mortality. Most interestingly, Hosseini and colleagues³ used mediation analysis to assess whether the impact of preoperative anemia on outcomes was influenced by intraoperative RBC transfusion. Preoperative anemia was associated with 27% higher odds of operative mortality (odds ratio, 1.27; 99.5% CI, 1.00-1.61; P = .047), an effect that was mediated by intraoperative RBC transfusion by 76.8% (P = .047). Patients with preoperative anemia were more likely to receive intraoperative transfusions (34% vs 8%; P < .001), and their risk of postoperative transfusion was found to be 2-fold higher than that in nonanemic patients. Intraoperative RBC transfusion largely mediated the effects of anemia on intensive care unit length of stay (99.9%) and hospital length of stay (76.7%).

Previous studies have argued the relative clinical importance of anemia vs transfusion. In 2013, our group⁴ reported that RBC transfusion is closely associated with risk-adjusted morbidity and mortality compared with preoperative anemia alone, a finding suggesting that transfusion is the bigger offender. The current study, reporting data on a large cohort through a unique statistical approach, suggests that transfusion explains a component of the additional risk in anemic patients. Whether the greater culprit is the anemia or the transfusion, both are targets that we can optimize. Perhaps the answer lies in addressing anemia preoperatively. In a recent randomized trial, Spahn and colleagues⁵ reported on reduced blood product transfusion and postoperative adverse events in anemic cardiac surgical patients who received a combination of intravenous iron, subcutaneous erythropoietin alpha, vitamin B₁₂, and oral folic acid.

By questioning the efficacy of transfusion on survival and morbidity, the Hosseini and colleagues³ have highlighted the importance of early recognition and correction of preoperative anemia in elective CABG. Both anemia and transfusion are culprits in operative risk; however, correcting anemia preoperatively and minimizing transfusion intraoperatively and postoperatively provide the best opportunity to improve clinical outcomes.