Prolonged RBC Storage before Transfusion Increases Extravascular Hemolysis

Red blood cell transfusion, the most common procedure performed on hospitalized patients, is an indispensable component of modern medicine and establishing an adequate blood supply depends on the ability to store donated red cells safely.

Some countries have limited the maximum allowable storage duration for red cells to five weeks before transfusion, while in the USA, red blood cells can be stored for up to six weeks, but randomized trials have not assessed the effects of this final week of storage on clinical outcomes.

Scientists at the Columbia University Medical Center and their colleagues randomly assigned a group of 60 healthy volunteers to receive a unit of red blood cells that had been stored for 1, 2, 3, 4, 5, or 6 weeks. The volunteers were then monitored for 20 hours after transfusion. Chromium-51 (51Cr) post transfusion red cell recovery studies were performed and laboratory parameters measured before and at defined times after transfusion.

Routine laboratory parameters were measured and transferrin saturation and total iron binding capacity were calculated from the measured serum iron and unbound iron-binding capacity. Nontransferrin-bound iron was measured using an ultrafiltration assay and this method correlated well with other techniques. Plasma-free hemoglobin was measured by a modified cyanomethemoglobin method. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure Hepcidin and interleukin -6.

The authors found that extravascular hemolysis after transfusion progressively increased with increasing storage time. Longer storage duration was associated with decreasing post-transfusion red cell recovery, decreasing elevations in hematocrit, and increasing serum ferritin. After six weeks of refrigerated storage, transfusion was followed by increases in area under the curve (AUC) for serum iron, transferrin saturation, and nontransferrin-bound iron as compared with transfusion after one to five weeks of storage. Within hours after transfusion, seven of the nine volunteers who received the 6-week-old blood could not appropriately metabolize the damaged cells, thereby releasing large amounts of iron into their bloodstream.

Eldad A. Hod, MD. Assistant Professor of Pathology and senior author of the study said, “Based on the amount of iron circulating in the blood of the volunteers who received six-week-old blood, we'd predict that certain existing infections could be exacerbated. It's estimated that up to 10% to 20% of blood units used for transfusions have been stored for more than five weeks, so the number of patients who are likely to receive a unit of very old blood is substantial.” The study was published in the January 2017 issue of the Journal of Clinical Investigation.