Data from many randomized clinical trials (RCTs) have not found an impact of storage time of red blood cells on patient outcomes. A newly published paper, however, questions the outcome and validity of these RCTs noting inherent clinical, methodological, and statistical problems. Namely, study arms with substantially different ages of fresh and old cells are logistically difficult due to the nature of stocking blood, and many of the RCTs were not powered to detect small but possibly meaningful effects of storage time. In order to overcome some of these obstacles, researchers in Denmark examined observational data from adult patients in the National Danish Registries. All patients between 2008 and 2018 who received at least one transfusion were included; patients transfused within the last year or those receiving massive transfusions were excluded. Using marginal structural models with inverse probability weights to adjust for a number of covariates (e.g., blood type, sex, age, location, comorbidities, number and compatibility of transfusions), researchers emulated hypothetical RCTs. Over 28-days of follow-up, death occurred in 12.7% of patients, but they found that transfusing with fresher RBCs decreased 28-day mortality. Specifically, 28-day mortality was 2.44 percentage points higher in patients transfused RBC units stored more than one week compared to RBC units stored one week or less (95% C.I. 0.86 to 4.02 percentage points). Further understanding of RBC age is needed in the context of the currently available randomized trials and pathophysiology.
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