Does prolonged storage of red blood cells cause harm?

Abstract

Red blood cells (RBCs) degrade progressively during the weeks of refrigerated storage. No universally accepted definition of 'fresh' or 'old' RBCs exists. While practices vary from country to country, preservative solutions permitting shelf life as long as 7 weeks have been licenced. Transfusion of stored RBCs, particularly those at the end of the approved shelf life, has been implicated in adverse clinical outcomes. The results of observational analyses, animal models and studies in volunteers have proved provocative, controversial and contradictory. A recently completed randomized controlled trial (RCT) in premature infants exemplifies the difficulties with moderately sized clinical studies. Several other RCTs are in progress. The effect of RBC storage may well vary according to the clinical setting. Resolution of the importance of the storage lesion may require large pragmatic clinical trials. In the meantime, institutions involved in blood collection and transfusion should explore strategies that assure blood availability, while limiting the use of the oldest RBCs currently approved by regulation.

Keywords: adverse effects; red blood cells; red cell units; storage; therapy.

Fig. 1

Possible temporal patterns connecting red blood cell (RBC) storage time with outcome. The hypothetical models represent 5 different temporal patterns linking the RBC storage time with the probability of adverse clinical outcomes. Modified and reprinted from: Pereira, A. (2013) Will clinical studies elucidate the connection between the length of storage of transfused red blood cells and clinical outcomes? An analysis based on the simulation of randomized controlled trials. Transfusion, 53, 34–40. with permission from Wiley.

Fig. 2

Survival curves in Staphylococcus aureus-challenged dogs. Kaplan-Meier plots over the 96 h course of 12 dogs exchange transfused with 42-day-old red blood cells (RBCs; solid circle, solid line) and 12 dogs exchange transfused with 7-day-old RBC (open circle, dashed line). Reprinted from Solomon et al, (2013).

Fig. 3

The RBC storage lesion. The changes affect the RBC cytoplasm and more so the membrane, parts of which are shed into the supernatant as microvesicles. RBC, red blood cell; 2,3-DPG, 2,3-diphosphoglycerate; ATP, adenosine triphosphate; ADP, adenosine diphosphate; AMP, adenosine monophosphate; IL, interleukin; TNF, tumour necrosis factor.