There was no indication that the storage period of transfused red blood cell (RBC) units impacted recipient survival, according to randomized controlled trials (RCTs). However, because of the inherent problems in performing RBC transfusion RCTs, its design, analysis, and interpretation have been criticized. For a study, in order to further highlight the negative consequences of storage time, researchers simulated hypothetical randomized trials using massive real-world data. 

Using inverse probability weighting, they assessed the comparative effect of transfusing only older versus fresher RBC units on the primary outcome of death and the secondary composite end point of thromboembolic events, or death. Storage thresholds were set at 1, 2, 3, and 4 weeks. The observational data was derived from a large Danish blood transfusion database containing over 900,000 transfusion episodes from 2008 to 2018. The qualifying criteria were satisfied by 89,799 patients who received >340,000 RBC transfusions over the course of 28 days. 

When compared to transfusing exclusively older RBC units, treatment with RBC units fresher than 1, 2, 3, and 4 weeks of storage reduced 28-day recipient mortality by 2.44 percentage points (pp) (0.86 pp, 4.02 pp), 1.93 pp (0.85 pp, 3.02 pp), 1.06 pp (-0.20 pp, 2.33 pp), and -0.26 pp (-1.78 pp, 1.25 pp). The composite end point’s 28-day risk differences were comparable. The study revealed that transfusing only older RBC units that have been held for more than one or two weeks increases 28-day recipient mortality and the risk of thromboembolism or death as compared to transfusing fresher RBC units.