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 haemolysed 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 haemolysis 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)
  • hypomagnesaemia
  • 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, patients receiving these RBCs will be exposed to “storage lesions”

SUSCEPTIBILITY OF THE  CRITICALLY ILL

Critically ill patients may be particularly susceptible 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)
  • Pettilä, 2011: prospective, multicenter observational study
    • 47 ANZ ICUs during a 5-week period between August 2008 and September 2008
    • n = 757 critically ill adult patients receiving at least one unit of RBCs
    • compared hospital mortality according to quartiles of exposure to maximum age of RBCs without and with adjustment for possible confounding factors
    • odds ratio for hospital mortality for patients exposed to the older three quartiles (mean RBC age 22.7d) compared with the lowest quartile (mean RBC age 7.7d) was 2.01 (95%CI = 1.07 to 3.77)
    • unadjusted ARR in hospital mortality of 8.1% (95% CI = 2.2 to 14.0%)
  • 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. 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. PMID:18354101.
  • 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. 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.PMC3883449.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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