Storage parameters affecting red blood cell survival and function after transfusion

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A LTHOUGH OUR understanding of the various parameters influencing the collection, separation, and storage of blood cells has progressively improved during past decades, with the exception of apheresis technologies, there have been surprisingly few advances in the practice of routine blood collection and component separation. This review attempts to summarize recent developments and to suggest steps that might be taken to improve the quality of stored red blood cells (RBCs) to maximize their safety and their benefits for the transfused recipient. The RBC is a highly specialized cell .without a nucleus and devoid of protein synthesis. This means that it has to rely on its original contents of enzymes and other proteins for the whole of its limited lifetime. In addition, because it lacks mitochondria, it cannot use oxidative phosphorylation for adenosine triphosphate (ATP) regeneration but has to rely on metabolizing glucose to lactate. This results in a net gain of 2 moles of ATP, 2 H +, and 2 moles of lactate per 1 mole of glucose metabol ized--an ineffective mechanism for energy supply compared with mitochondrial oxidation via the citric acid cycle. Approximately 10% of the metabolic flux passes by way of the pentose phosphate pathway in which oxygen is consumed and carbon dioxide formed. A simplified metabolic outline is presented in Figure 1, which also illustrates some substances that can be used to influence the metabolism under in vitro storage conditions. The most important function of RBCs, oxygen transport, exposes the cell to toxic oxygen species, free oxygen radicals such as O 2 and OH', and to hydrogen peroxide. For protection against denaturation by peroxidation of the lipids in the membrane bilayer, its proteins and enzymes, a number of antioxidants such as vitamin E are available in both the liquid and cellular components of the blood, and redox machinery is provided within the red cell. A highly flexible membrane is essential for rapid uptake and release of oxygen and carbon dioxide. In this way, the RBC will have a great contact surface area between its own membrane and that of the capillaries as it rolls through these vessels like a small wheel with a big flat tire. This rolling also helps mix the viscous intracellular content. The degree of saturation of the RBC hemoglobin (Hb) and its dependence on the surrounding partial pressure of oxygen (pO2), can be graphically represented by a sigmoidal curve, the oxygen dissociation curve (ODC). The inflection point of this curve is at 50% Hb saturation. This point, the p50, normally has a value of approximately 3.6 kPa (27 mm Hg). The factors that most potently influence p50 are pH (H + and CO2) and 2,3-diphosphoglycerate (2,3-DPG). As pH is lowered, the ODC is shifted to the right, which means that the affinity of Hb for oxygen is reduced, oxygen is less readily bound and more readily released. In the normally functioning lung, pO2,is sufficiently high to result in nearly complete saturation, at both normal and moderately rightshifted ODC. In the peripheral circulation, the pH is lower than in the lungs, which promotes oxygen release. If the ODC is left-shifted, less oxygen will be delivered at a certain pO2. Because of competition between 2,3-DPG and oxygen at the same site on the Hb molecule, an increased concentration of 2,3-DPG will cause reduced oxygen affinity and a right shift of the ODC. Patients with chronic anemia usually have an increased erythrocyte 2,3-DPG concentration and a right-shifted ODC, which seems to give some compensation for the lower concentration of circulating cellular Hb. All currently used methods for the liquid storage of RBCs result in depletion of 2,3-DPG, generally after I to 2 weeks of storage. These RBCs will have a left-shifted ODC, greater oxygen affinity, and may supply less oxygen to the tissues. Cells with depleted 2,3-DPG will normalize within 48 to 72 hours after transfusion. 1-3