Effects of storage‐aged red blood cell transfusions on endothelial function in hospitalized patients

Abstract

Background Clinical and animal studies indicate that transfusions of older stored RBCs impair clinical outcomes as compared to fresh RBC transfusions. It has been suggested that this effect is due to inhibition of NO-mediated vasodilation following transfusion of older RBC units. However, to date this effect has not been identified in human transfusion recipients. Study Design and Methods Forty-three hospitalized patients with transfusion orders were randomized to receive either fresh (< 14 days) or older stored (> 21 days) RBC units. Prior to transfusion, and at selected time points after the start of transfusion, endothelial function was assessed using non-invasive flow-mediated dilation assays. Results Following transfusion of older RBC units, there was a significant reduction in NO-mediated vasodilation at 24 hours after transfusion (p=0.045), while fresh RBC transfusions had no effect (p=0.231). Conclusions The present study suggests for the first time a significant inhibitory effect of transfused RBC units stored > 21 days on NO-mediated vasodilation in anemic hospitalized patients. This finding lends further support to the hypothesis that deranged NO signaling mediates adverse clinical effects of older RBC transfusions. Future investigations will be necessary to address possible confounding factors and confirm these results.

Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis

“…26,27 Of the 3 articles that underwent full text review, one 36 did not report the patient-important outcomes we sought. Of the 16 trials included in the recent Cochrane review, 25 we judged 6 to be ineligible 36-41 because they did not report the outcomes examined in this review, leaving a total of 12 eligible studies.…”

Established and theoretical factors to consider in assessing the red cell storage lesion

“…55 Thus, additional metrics of RBC storage have been added to the above-mentioned details, including distinguishing hemoglobin outside of intact RBCs (eg, either free or in the form of microparticles that may scavenge NO), the amount of S-nitrosylation of hemoglobin itself (SNO-Hg), 55 adhesion of RBCs to endothelial beds, 56 effects of stored RBCs on models of vascular tone (eg, isolated aortic rings), 57 and in vivo measures of how stored RBCs affect vascular tone, both in animals and directly in humans. 58 However, as with the long list of more traditional measures, the clinical meaning of these indications remains largely undetermined (and in some cases controversial) and the ability to predict RBC function is unclear.…”

Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function

“…However, in these studies the mean ages of older blood were only 22 and 28.3 days, respectively, and very few units of blood were transfused at the extreme limits of FDA-approved storage of 42 days (16)(17)(18). Thus, although transfusion of blood may increase risk (12,13,15,19), whether this risk is compounded by storage age, especially at the limits of storage and in the setting of larger transfusion volumes, remains unclear (20)(21)(22)(23)(24).…”

“…In contrast, in a followup study the same group evaluated a single unit transfusion of autologous 40-daystored leukoreduced red cells into subjects with endothelial dysfunction and demonstrated increased post-transfusion levels of CFPHb, NO consumption, and pulmonary artery pressures estimated by Doppler echocardiography (23,31). Similarly, Neuman and colleagues (24) demonstrated that individuals with anemia receiving aged blood (.21 d) had evidence of endothelial dysfunction at 24 hours post-transfusion.…”

“…Several recent studies have assessed vascular endothelial function in normal human volunteers after transfusion of autologous blood (23,24,31). Berra and colleagues (31) reported that 1-U transfusion of 40-day-aged red cells did not affect the reactive hyperemia index, a noninvasive measure of endothelial function, compared with transfusions of 3-day-aged red cells.…”