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| Now that's a office style storage lesion! |
Blood Storage Lesion: What Happens to Blood During Storage?
Another kind of storage lesion...
Blood components do not remain biologically unchanged after collection. During storage, red blood cells (RBCs) and platelets undergo progressive biochemical, metabolic, and structural changes collectively referred to as storage lesions.
These changes are easy to demonstrate in the laboratory. The more complicated question is whether they meaningfully affect patients after transfusion.
What Is the Red Blood Cell Storage Lesion?
Red blood cells are stored under refrigerated conditions in preservative and additive solutions designed to maintain their viability for several weeks. Even under these controlled conditions, RBC metabolism continues and the cells gradually change.
Common features of the RBC storage lesion include:
Decreased ATP: ATP is required to maintain membrane structure, ion gradients, and RBC deformability.
Decreased 2,3-DPG: Loss of 2,3-DPG temporarily increases hemoglobin's affinity for oxygen, although 2,3-DPG is regenerated after transfusion.
Decreased pH: Continued glycolysis produces lactate and progressively acidifies the storage environment.
Increased extracellular potassium: Potassium leaks from RBCs as membrane ion gradients deteriorate during refrigerated storage.
Increasing hemolysis and free hemoglobin: A small proportion of RBCs rupture during storage.
Loss of membrane deformability: Stored RBCs undergo membrane and cytoskeletal changes that can make them less flexible.
Oxidative damage: Reactive oxygen species can modify membrane proteins, lipids, and hemoglobin.
Formation of extracellular vesicles: Portions of the RBC membrane may be shed as small vesicles during storage.
Measurements of stored RBCs consistently demonstrate changes such as declining ATP and 2,3-DPG, increasing hemolysis, and alterations in membrane properties as storage progresses.
Why Does Potassium Increase in Stored RBCs?
The RBC membrane normally maintains a high intracellular potassium concentration through active ion transport. Refrigeration slows cellular metabolism and membrane pumps, allowing potassium to gradually leak from RBCs into the extracellular storage solution.
This means that an older RBC unit can contain substantially more extracellular potassium than a freshly collected unit.
For most routine adult transfusions, this does not cause a clinically important problem. However, the potassium load can become more relevant when RBCs are transfused very rapidly or in large volumes, or in particularly vulnerable patients.
Storage is also accompanied by increasing hemolysis, which contributes additional intracellular material to the supernatant. Increasing extracellular potassium and hemolysis during RBC storage have been repeatedly demonstrated experimentally.
Does the RBC Storage Lesion Reduce Oxygen Delivery?
Potentially—but the relationship is more complicated than simply saying that "old blood carries less oxygen."
One important change is depletion of 2,3-DPG, which causes hemoglobin to bind oxygen more tightly. RBC deformability also declines during storage, potentially affecting the ability of cells to move through the microcirculation.
These laboratory changes led to concern that older RBC units might provide inferior tissue oxygen delivery or produce inflammatory and vascular effects after transfusion.
That concern prompted several large clinical trials.
Platelet Storage Lesion
Platelets develop a different storage lesion because they are stored under very different conditions from RBCs.
During storage, platelets can undergo progressive activation and metabolic and structural changes that reduce their ability to circulate and function normally after transfusion.
Changes associated with platelet storage include:
Progressive platelet activation
Loss of normal discoid shape
Changes in membrane glycoproteins
Release of granule contents and soluble mediators
Declining mitochondrial and metabolic function
Reduced responsiveness to agonists
Increasing evidence of apoptosis and loss of viability
Reduced post-transfusion recovery and survival as storage time increases
Bacterial growth is also an important concern during platelet storage because platelets are stored at room temperature. However, bacterial contamination is better considered a storage-associated infectious risk rather than part of the platelet storage lesion itself.
Are Fresher Red Blood Cells Better?
Biologically, fresh and older RBC units are clearly different.
Clinically, however, that has not translated into a general benefit from routinely transfusing fresher blood.
The ABLE trial, published in 2015, randomized more than 2,400 critically ill adults to receive either RBCs stored for less than eight days or standard-issue RBCs. The fresh units had been stored for an average of about six days compared with about 22 days in the standard group.
There was no significant reduction in 90-day mortality with fresher RBCs, and there were no significant differences in the major secondary outcomes evaluated in the trial.
The much larger INFORM trial subsequently compared the freshest available compatible RBCs with standard blood-bank practice and likewise found no mortality advantage from transfusing fresher RBCs.
The TRANSFUSE trial, involving critically ill adults, reached the same basic conclusion: transfusing the freshest available RBCs did not improve 90-day survival compared with standard-issue RBCs.
Together, these trials substantially changed how the clinical significance of the RBC storage lesion is viewed.
The Storage Lesion Is Real—But Its Clinical Importance Is Complicated
There is no question that RBCs change during storage. ATP and 2,3-DPG decline, potassium accumulates in the supernatant, membrane properties change, extracellular vesicles form, and hemolysis gradually increases.
What has been much harder to demonstrate is that routinely giving patients fresher RBCs produces better outcomes.
Large randomized trials have failed to show improved mortality or major clinical outcomes when fresher RBCs are used instead of appropriately stored standard-issue units.
That does not mean storage age is irrelevant in every situation. Particular patient populations and transfusion circumstances may make specific characteristics of stored RBCs—such as extracellular potassium—more important.
For routine transfusion practice, however, there is currently no strong evidence that patients benefit from receiving the freshest available RBC unit simply because it is fresher.
Modern blood banking therefore has to balance two realities: blood cells unquestionably deteriorate during storage, but appropriately stored blood remains effective for transfusion throughout its approved shelf life.