A patient recovering from long term critical illness was found to have a Hb of 65G/L.
You request 3 units of packed RBCs. The blood bank informs you that the patient has an uncommon blood group and the only blood available although safe, is nearing the end of its storage life.
Outline the factors that may contribute to the reduced efficacy of such blood and what clinical consequences might be expected?
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.
- 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.
Storage lesions of packed red blood cells are discussed in greater detail in another chapter
One can also find an (out of date) Blood Service Policy on "The Age of Red Cells" from the Australian Red Cross.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
- 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.