Extravascular Hemolytic Reactions
Delayed extravascular hemolytic reactions are most likely due to previous sensitization to red cell antigens from prior transfusion, pregnancy, or transplant. Extravascular hemolysis can occur days to weeks after repeat exposure. Patients present with fever, anemia, and jaundice without hemoglobinemia or hemoglobinuria. Symptoms are usually benign, though oliguria and DIC have been reported.27,28
Transfusion-associated graft-versus-host disease is a delayed extravascular hemolytic reaction that occurs in immunosuppressed recipients of transfused blood. Most deaths are due to coagulopathy or infection. Transfused lymphocytes proliferate and attack the blood recipient. Symptoms (eg, fever, rash, diarrhea, elevated liver transaminases, pancytopenia) begin 3 to 30 days posttransfusion, and a bone marrow transplant is indicated. Irradiated and leukoreduced blood components prevent TA-GVHD.29,30
Bacteremia and Viral Infection
Among significant bacterial contaminants from donor blood, Yersinia enterocolitica is the most common and has a mortality rate of greater than 50%.31 Typical symptoms include rigors, vomiting, abdominal cramps, fever, shock, renal failure, or DIC during transfusion. Immediate cessation of blood products and broad spectrum antibiotics are warranted. Risks among viral contaminants include human immunodeficiency disease (HIV), CMV, and hepatitis. Hepatitis B infection occurs in one in 1 million transfusion recipients, while the risk of hepatitis C is one in 1.2 million and HIV infection one in 1.5 million.32,33
Electrolyte Derangement
Electrolyte derangements after multiple-unit transfusions include hypocalcemia, hyperkalemia, and acid-base disorders. Massive blood transfusions with blood anticoagulated with sodium citrate and citric acid may contribute to metabolic alkalosis and hypocalcemia. Potassium may move into cells in exchange for hydrogen ions moving out of cells to minimize extracellular alkalosis, contributing to hypokalemia.34-36 To avoid hypocalcemia and alkalosis, the maximum citrate infusion rate should be 0.02 mmol/kg/minute, with the citrate concentration in whole blood measured as 15 mmol/L. If liver function is impaired in the setting of hypocalcemia-related blood transfusion, calcium chloride is preferred over calcium gluconate because it decreases citrate metabolism resulting in a slower release of ionized calcium.37 Calcium replacement should be considered in patients with liver dysfunction or patients with normal liver function who have received greater than 10 U pRBCs per hour. Calcium chloride (10%) is preferred over calcium gluconate to correct ionized hypocalcemia with 2 to 5 mL given for every 500mL of blood.37 Hyperkalemia risks are minimized by avoiding prolonged blood storage or irradiation.38
Conclusion
Timely administration of blood products is crucial in resuscitation and can be life-saving in a variety of bleeding disorders. Emergent reversal of warfarin therapy, correction of thrombocytopenia, bleeding due to hemophilia, GI bleeding, trauma, and obstetric hemorrhage are among the most common disorders managed in the ED. To select the most appropriate treatment, one must know the merits of the various blood products including PRBCs, platelets, FFP, and cryoprecipitate. The clinician must also be prepared to manage the immediate complications that may arise from transfusion including intravascular hemolytic reactions, fever, urticaria, and TRALI, as well as the delayed complications of extravascular hemolytic reactions, TA-GVHD, acute bacteremia, viral infection, electrolyte derangements, cardiogenic pulmonary edema, and TACO.
Dr Stewart is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, Virginia, and Riverside Medical Group, Newport News, Virginia. Dr Devine is an emergency physician in the department of emergency medicine, Eastern Virginia Medical School, Norfolk, and Emergency Physicians of Tidewater, Norfolk, Virginia. The authors report no conflicts of interest.