Storage Lesions

Reviewed and revised 14 January 2014

OVERVIEW

• Storage lesions are the adverse effects associated with the storage of blood
• begins after about 2 weeks of storage and progresses with duration of storage (‘RBC age’)
• RBCs undergo structural and functional changes that reduce function and viability after transfusion
• critically ill patients may be especially susceptible to the adverse effects of prolonged RBC storage

SHORT TERM EFFECTS

RBC integrity

• membrane vesiculation and decreased deformability, which impedes microvascular flow and triggers inflammation
• increased adhesiveness and aggregability
• haemolysis over time

Accumulation or depletion of important chemicals and mediators

• depletion of 2, 3 DPG (causes left shifted oxy-Hb dissociation curve, which reduces O2 delivery)
• reduced concentration of NO
  – free Hb from hemolysed old cells scavenges NO
  – leads to endothelial dysfunction and contributes to intravascular thrombosis, vasoconstriction, and leukocyte adhesion)
• reduced ATP, leads to reduced ability to maintain biconcave shape
• accumulation of proinflammatory bioactive substances (lipids that activate neutrophils and may cause TRALI, cytokines and free iron)
• WBCs present in RBC units (cause hemolysis and potassium release, liberate oxygen radical, and increase erythrocyte alterations)

Effects on electrolytes and metabolic state

• progressive increase in K+ concentration (20mmol/L @ day 28)
  – despite this significant hyperkalaemia is an uncommon complication of transfusion
• progressive acidaemia (pH 6.7 @ day 28)
• hypomagnasaemia
• citrate exposure, which causes hypocalcaemia

LONG TERM EFFECTS

• increased peri-operative complications
• renal failure
• multiple organ failure
• nosocomial infection
• mortality
• VTE
• increased duration of mechanical ventilation
• increased hospital LOS

CURRENT PRACTICE

• standard practice worldwide consists of transfusing the oldest compatible and available RBC unit
• this avoid wasting RBC units and improves supply
• RBC can be stored up to 42 days, based on >75% RBC still present in the circulation 24 hours after transfusion and hemolysis <1% at the end of the storage period
• mean age varies from 16 to 21 days
• Despite improved preservation methods, pateints receiving these RBCs will be exposed to “storage lesions”

SUSCEPTIBILITY OF THE  CRITICALLY ILL

Critically ill patients may be particularly suscveptible to the effects of storage lesions

• pre-existing impaired microcirculatory flow
• neutrophils may be primed by a trigger event (e.g., sepsis or trauma) leading to enhanced activation (e.g. ‘two hit’ model of TRALI)
• mechanical ventilation may predispose to TRALI
• ‘dose effect’ of multiple transfusions (more likely to receive more units of old RBCs)

EVIDENCE

Summary

• Multiple retrospective, observational, and single-center studies have been performed to assess the effect of blood storage duration on morbidity and/or mortality in trauma, cardiac surgery, and intensive care unit patients
• most studies are small and subject to bias
• findings are conflicting and heterogeneous, but meta-analysis suggests increased mortality from use of older stored blood
• there is a need for definitive large MC RCTs: TRANSFUSE studyof ICU patients by the ANZICS CTG is currently in progress, as is the RECESS cardiac surgery study and the Canadian ABLE study

Studies

• Recent meta-analysis by Wang et al (2013) found use of older stored blood is associated with significantly increased risk of death
  • 21 studies, n ~ 410,000, cardiac surgery and trauma patients predominantly
  • Increased mortality risk with older blood (OR 1.16)

• Koch et al, 2008
  • retrospective single-center study
  • n = 6,002 patients undergoing CABG and/or valve surgery (no adjustment for confounders)
  • transfusion of RBC aged > 14 days old associated with:

-> longer duration of mechanical ventilation
-> sepsis
-> serious adverse
-> mortality at 1 year

• Other studies in other patient groups (e.g. trauma)

-> DVT
-> multi-organ failure
-> sepsis
-> death

References and links

Journal articles

• Aubron C, Nichol A, Cooper DJ, Bellomo R. Age of red blood cells andtransfusion in critically ill patients. Ann Intensive Care. 2013 Jan 15;3(1):2.doi: 10.1186/2110-5820-3-2. PubMed PMID: 23316800; PubMed Central PMCID:PMC3575378.
• Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, BlackstoneEH. Duration of red-cell storage and complications after cardiac surgery. N EnglJ Med. 2008 Mar 20;358(12):1229-39. doi: 10.1056/NEJMoa070403. PubMed PMID:18354101. [Free Full Text]
• Pettilä V, Westbrook AJ, Nichol AD, Bailey MJ, Wood EM, Syres G, Phillips LE,Street A, French C, Murray L, Orford N, Santamaria JD, Bellomo R, Cooper DJ;Blood Observational Study Investigators for ANZICS Clinical Trials Group. Age ofred blood cells and mortality in the critically ill. Crit Care. 2011;15(2):R116.doi: 10.1186/cc10142. Epub 2011 Apr 15. PubMed PMID: 21496231; PubMed CentralPMCID: PMC3219399.
• Wang D, Sun J, Solomon SB, Klein HG, Natanson C. Transfusion of older storedblood and risk of death: a meta-analysis. Transfusion. 2012 Jun;52(6):1184-95.doi: 10.1111/j.1537-2995.2011.03466.x. Epub 2011 Dec 21. Review. PubMed PMID:22188419; PubMed Central PMCID: PMC3883449.