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Red cell transfusion is one of the oldest and most commonly employed therapies in medicine. The first successful stored red cell transfusions occurred fewer than 100 years ago. The special place of red cell transfusion in medical practice is the result of its lifesaving applications in exsanguinating hemorrhage and life-threatening anemia, for which transfusion remains today virtually the only effective therapy. Methods of red cell preservation have been improved, and the risks of hemolytic transfusion reactions and transmission of infectious diseases significantly reduced. Red cell transfusion is used both to prevent complications of anemia and to treat the symptoms and signs of hypoxia due to anemia. These signs generally do not develop unless hemoglobin level falls below 5 g/dL. Nonetheless, common clinical practice is to maintain hemoglobin levels above 7 g/dL in most patients, and above 8 g/dL in those patients with symptomatic coronary artery disease. In transfusion-dependent outpatients, transfusion to hemoglobins of 9 to 11 g/dL is considered to provide improved quality of life with modest risk, but scant data support the safety of this practice employing transfusion as opposed to erythropoietic agents. In patients with severe hereditary hemoglobinopathies, transfusion also serves to reduce the production of abnormal red cells, in some cases decreasing pathologic effects, as well as provide therapy of the anemia. Alternative strategies exist but cannot fully substitute for transfusion of donor red cells. Transfused stored red cells are not normal, having reduced or absent 2,3-biphosphoglycerate and nitric oxide, and abnormal biophysical properties. The exact importance of these changes to transfusion efficacy and safety is not known. Adverse effects of red cell transfusion related to immunologic incompatibility and disease transmission are uncommon to rare, especially in the era of modern serologic and microbial testing, and use of leukoreduced red cells, but uncommon mild allergic reactions can occur, and are prevented by saline washing or plasma removal of red cells. Acute lung injury is rare after red cell transfusion, but can be life-threatening. Circulatory overload as a result of too rapid or too high volume red cell transfusion is more frequent than lung injury, but less likely to be fatal, and more easily managed in most cases. The potential toxicity and questionable efficacy of stored red cells are now major foci of clinical concern and research. Immunomodulation leading to increases in infection, tumor recurrence, multiorgan failure, decreased organ allograft rejection, and similar phenomena is an important area of basic and clinical research. Preliminary findings raise the question of whether red cell transfusion may predispose to arterial and venous thrombosis. Storage duration of transfused red cells has become one issue in these associations with transfusion. Leukoreduction of red cell transfusions reduces alloimmunization to human leukocyte antigens, cytomegalovirus transmission, refractoriness to platelet transfusion, febrile transfusion reactions, and multiorgan failure after cardiac surgery. Leukoreduction has become standard practice throughout most of the developed world, but has not been adopted universally in the United States. Red cell transfusion remains a key therapy prescribed by physicians of all specialties, ...

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