Question 29.1

College Answer

Storage lesions begin after 2 to 3 weeks of storage and progress with duration of storage – with storage RBCs undergo structural and functional changes that may reduce function and viability after transfusion.

Effects include: 

• Decreased deformability which impedes microvascular flow
• depletion of 2,3 DPG shifts oxyhaemoglobin curve to the left and reduces O2 delivery
• increased adhesiveness and aggregability
• reduced concentrations of nitric oxide (bound as nitrosothiol,SNO)
• reduced  ATP
• reduced ability to maintain biconcave shape
• accumulation of proinflammatory bioactive substances

Transfusion  of  red  cells  stored  for  more  than  14  days  has  been  associated  with increased  peri  operative  complications  ,  organ  failure  ,  sepsis  and

 mortality  after cardiac surgery ( Koch, NEJM: 2008 ).
In particular survival in the first 6 months after surgery was reduced.
Other studies have demonstrated an association between an increased duration of storage and multiorgan failure, sepsis and death in other populations including post surgical and general ICU patients.

Discussion

Storage lesions of packed red blood cells are discussed in greater detail elsewhere.

One can also find an (out of date)  Blood Service Policy on "The Age of Red Cells" from the Australian Red Cross.Theoretical objections to the use of old PRBCs are raised by Aubron et al in their 2013 article.

In brief summary, the storage lesions are as follows:

• Decreased 2,3-DPG levels (thus, left shift of the oxyhaemoglobin dissociation curve)
• Decreased ATP levels
• Decreased deformability of erythrocytes
• Red cell membrane vesciculations
• Haemolysis and the release of free haemoglobin
• Accumulation of toxic byproducts, esp. potassium and lactate
• Accumulation of proinflammatory molecules

Thus, the almost-expired blood has a number of disadvantages:

• Poor oxygen transport
• Poor microvascular perfusion
• Inflammatory potential

The clinical consequences of transfusing someone with such blood?

• The Koch paper from NEJM (2008) which is quoted by the college is not a small trial (in total 5002 patient were enrolled) and it indeed found a strong association between the infusion of older PRBCs with some serious adverse outcomes, such as:
  •  In-hospital mortality
  • 1-year mortality
  • Length of intubation >72 hrs
  • Renal failure
  • Sepsis

• Increased mortality was confirmed according to a 2012 meta-analysis of multiple RCTs
• Higher risk of developing multi-organ system failure was also a consistent finding of the various trials

However, on meta-analysis, some of the other adverse effect risks were not supported:

• No evidence for increased ICU stay
• No evidence for increased duration of ventilation
• No evidence for increased risk of hospital-acquired infection
• No evidence for increased risk of renal failure
• Apart from the abovementioned positive studies, 14 other studies failed to demonstrate any increase in mortality.

More recent evidence from the ABLE trial  (Lacroix et al, 2015) confirms essentially all of the above. The authors could not find any difference in any of the outcomes between the patients who got 6-day-old cells and those who got 22-day-old cells. Results of the AustralianTRANSFUSE study are still awaited, but generally speaking it is becoming apparent that the theoretical disadvantages of using older PRBCs do not materialise in practice.

Wang, Dong, et al. "Transfusion of older stored blood and risk of death: a meta‐analysis." Transfusion 52.6 (2012): 1184-1195.

 

Aubron, Cécile, et al. "Age of red blood cells and transfusion in critically ill patients." Ann Intensive Care 3.1 (2013): 2.

 

 

Koch, Colleen Gorman, et al. "Duration of red-cell storage and complications after cardiac surgery." New England Journal of Medicine 358.12 (2008): 1229-1239.

 

Lacroix, Jacques, et al. "The Age of Blood Evaluation (ABLE) randomized controlled trial: study design." Transfusion medicine reviews 25.3 (2011): 197-205.