Acute hemolytic reactions usually are caused by preformed IgM antibodies against donor red cells that fix complement. They most commonly stem from an error in patient identification or tube labeling that allows a patient to receive an ABO incompatible unit of blood. Preexisting “natural” IgM antibodies, usually against blood group antigens A or B, bind to red cells and rapidly induce complement-mediated lysis, intravascular hemolysis, and hemoglobinuria associated with fever, shaking chills, and flank pain. The direct Coombs test is positive unless all of the donor red cells have lysed. The signs and symptoms are due to complement activation rather than hemolysis per se, as osmotic lysis of red cells (e.g., by mistakenly infusing red cells and 5% dextrose in water simultaneously) produces hemoglobinuria without any other symptoms. In severe cases the process may rapidly progress to DIC, shock, renal failure, and death.
Delayed hemolytic reactions are caused by antibodies that recognize red cell antigens that the recipient was sensitized to previously, for example, through a http://ebooksmedicine.net previous blood transfusion. These are typically caused by IgG antibodies and are associated with a positive direct Coombs test and laboratory features of hemolysis (e.g., low haptoglobin and elevated LDH). Antibodies to antigens such as Rh, Kell, and Kidd sometimes fix complement, resulting in severe and potentially fatal reactions identical to those seen with ABO mismatches. Other antibodies that do not fix complement typically result in extravascular hemolysis and relatively minor signs and symptoms.
Transfusion-related acute lung injury (TRALI) is a severe, frequently fatal complication in which factors in a transfused blood product trigger the activation of neutrophils in the lung microvasculature. The incidence is low, probably less than 1 per 10,000 transfusions. Current thinking about TRALI favors a “two hit” hypothesis. The first hit is an exposure that activates endothelial cells in pulmonary capillaries. This “priming” event has diverse causes, including smoking, sepsis, and shock, and leads to sequestration of neutrophils. The primed neutrophils are then activated by a factor present in the transfused blood product, which constitutes the second hit.
The leading “second hit” candidate is an antibody in the transfused blood product that recognizes antigens expressed on neutrophils. By far the most common antibodies associated with TRALI are those that bind major histocompatibility complex (MHC) class I antigens. These antibodies are often found in multiparous women, in whom they are generated in response to foreign MHC antigens expressed by the fetus. Indeed, measures to exclude multiparous women from plasma donation have resulted in the incidence of TRALI being cut in half. The presentation is dramatic, with sudden onset of respiratory failure associated with diffuse bilateral pulmonary infiltrates during or soon after a transfusion. The treatment is largely supportive and the outcome is guarded; mortality is 5% in uncomplicated cases and up to 67% in those who are severely ill.
Virtually any infectious agent can be transmitted through blood products, but bacterial and viral infections are most likely to be so. Significant bacterial contamination (sufficient to produce symptoms) is much more common in platelet preparations than red cell preparations, because of the fact that platelets (unlike red cells) must be stored at room temperature, which favors growth of bacterial contaminants. Rates of bacterial infection secondary to platelet transfusion can be as high as 1 in 5000. Many of the symptoms (fever, chills, hypotension) resemble those of transfusion reactions, and it may be necessary to start broad-spectrum antibiotics prospectively in symptomatic patients while awaiting laboratory results.