Patient Blood Management Guidelines: Module 1

Critical Bleeding Massive Transfusion

| Background |

3.6 Blood

3.6.1 Age of transfused red blood cells

Storage of whole blood and blood components leads to numerous changes, often referred to as the ‘storage lesion’. The changes to RBCs include:

  • reduced levels of 2, 3 diphosphoglycerate
  • increased oxygen affinity
  • shape change
  • reduced deformability
  • decreased viability

The result is reduced tissue oxygenation and obstruction of the microcirculation, which may contribute to organ failure in critically ill patients. With increasing storage time, there is also generation of inflammatory mediators, cytokines and lipids; these have been implicated in immunomodulation, transfusion-related acute lung injury, febrile transfusion reactions and cellular injury.

The shelf-life of stored RBCs is currently up to 42 days, depending on the additive solution used. Additives used to buffer pH, prevent coagulation, delay the biochemical, metabolic and molecular changes, and preserve oxygen-carrying capacity include CPDA-1 (citrate, phosphate, dextrose and adenine) and SAG-M (sodium chloride, adenine, glucose and mannitol). The introduction of universal prestorage leukodepletion of RBCs may reduce storage lesion and its sequelae.

A key question is whether time-dependent changes have any measurable effect on patient outcomes. Studies of the effect on tissue oxygenation,42-44 blood chemistry,45 cognitive function and neurological recovery46 have reached different conclusions. Some studies have claimed an association between older blood and increased incidence of venous thromboembolism,47 severe infections,48,49 multiorgan failure50 and mortality.47,51,52

Limitations of existing studies include variability in study populations, study size, confounding effects of transfusion volume, varying definitions of ‘young’ and ‘old’ blood, and changes in production processes; for example, the introduction of leukodepletion. Most studies are analyses of registry-based data, and the observational design cannot address all important outcomes or account for all confounders. A randomised controlled trial (RCT) failed to find an effect of age of blood on tissue oxygenation in critically ill patients, or on cognitive performance in anaemic but otherwise healthy adults.42 Well-designed prospective studies are needed to determine whether storage time of RBCs affects clinical outcomes.

Currently, there is insufficient evidence to support restricting RBCs transfused to critically ill patients to blood stored for only a short period of time (e.g. < 14 days).