Can we be certain that storage duration of transfused red blood cells does not affect patient outcomes?BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l2320 (Published 11 June 2019) Cite this as: BMJ 2019;365:l2320
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Re: Can we be certain that storage duration of transfused red blood cells does not affect patient outcomes?
Thank you for this useful presentation of caveats surrounding the subject of duration of red cell storage and clinical outcomes. These studies have been widely interpreted as "no problem here" in assuming that transfusion is not associated with adverse clinical outcomes. I believe this is a serious misinterpretation of the data. In addition to the concerns raised by the authors, an additional valid hypothesis supported by these studies is that transfusions of very short storage and somewhat longer storage red cells may be equally toxic/dangerous. In other words, not good news at all.
One possibility that has received little attention is that very short storage red cells may be more dangerous than medium storage periods (say 7-21 days) and equally dangerous to longer storage red cells (say 28-42 days). An inverted U shaped curve, if you will. The evidence for this possibility is that meta-analysis of the existing studies found that ultra-short storage of red cells was associated with a post-transfusion increase in nosocomial infection. (1) . Shorter storage red cells have a greater imbalance of oxidation-reduction potential than longer storage red cells in preliminary studies in vitro (2). Red cell storage duration is also a poor predictor of post-transfusion free hemoglobin and heme, putative mediators of toxicity from transfusions (3, 4).
Thus we need better metrics of predictors of red cell transfusion efficacy and toxicity. Unfortunately the simple expedient of fresher red cells is clearly not that metric, and may indeed be leading us to transfusing more toxic red cells (very fresh) in the most fragile patients, such as premature newborns. A new approach not involving "very fresh" is clearly called for by the current data. At our center we define fresh as <21 days of storage, and generally never transfuse a red cell much less than 7-10 days in storage, for the above reasons as well as logistics of supply.
(1)Alexander PE, Barty R, Fei Y, Vandvik PO, Pai M, Siemieniuk RA, Heddle NM, Blumberg N, McLeod SL, Liu J, Eikelboom JW, Guyatt GH.Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis.
Blood. 2016 Jan 28;127(4):400-10.
(2)Schmidt A , Gore E, Cholette JM, Henrichs K, Conley GW , Dorsey C, Bjugstad KB, Refaai M, Blumberg N. Oxidation Reduction Potential (ORP) is Predictive of Complications following Cardiac Surgery in Pediatric Patients. Transfusion 56 [Supplement S4]: 20A-21A (2016). (abstract).
(3)Cholette JM, Pietropaoli AP, Henrichs KF, Alfieris GM, Powers KS, Gensini F, Rubenstein JS, Sweeney D, Phipps R, Spinelli SL, Refaai MA, Eaton MP, Blumberg N.Elevated free hemoglobin and decreased haptoglobin levels are associated with adverse clinical outcomes, unfavorable physiologic measures, and altered inflammatory markers in pediatric cardiac surgery patients.
Transfusion. 2018 Jul;58(7):1631-1639.
(4)Pietropaoli AP, Henrichs KF, Cholette JM, Spinelli SL, Phipps RP, Refaai MA, Blumberg N.
Total plasma heme concentration increases after red blood cell transfusion and predicts mortality in critically ill medical patients. Transfusion. 2019 Jun;59(6):2007-2015.
Competing interests: No competing interests