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  1. Transfusion Reactions
    1. Acute hemolytic transfusion reactions are estimated to occur in 1 in 250 000 transfusions and are usually due to a label or clerical error at the time of sample collection, bag labeling, or bedside infusion. Symptoms include anxiety, agitation, chest pain, flank pain, headache, dyspnea, and chills. Nonspecific signs include fever, hypotension (or cardiovascular collapse), unexplained bleeding (or disseminated intravascular coagulation [DIC]), and hemoglobinuria (or renal failure). Fatal reactions are estimated at 1 in 1 250 000 units. Table 34.2 describes the steps to be taken if a transfusion reaction is suspected.
    2. Nonhemolytic transfusion reactions are usually due to antibodies against donor white cells or plasma proteins. These patients may complain of anxiety, pruritus, or mild dyspnea. Signs may include fever, rigors, flushing, hives, tachycardia, tachypnea, and hypertension. The transfusion should be stopped and the possibility of a hemolytic transfusion reaction evaluated (see earlier text).
      1. If the reaction is only urticaria, the transfusion should be slowed and may be continued. Antihistamines (eg, diphenhydramine, 25-50 mg IV) are not required but may be given for symptomatic relief of itching. There is no role for antipyretics such as acetaminophen in allergic transfusion reactions. Urticarial reactions are usually not reproducible in subsequent transfusions. Routine pretransfusion use of antihistamines or antipyretics is not recommended.
      2. Patients with a prior history of febrile transfusion reactions should be transfused with leukoreduced pRBCs and platelets. Premedication is not recommended.
      3. Anaphylactic reactions occur rarely and have been associated in some studies with high-titer antibodies to IgA among patients with undetectable IgA. Transfusion of patients with a documented history of transfusion anaphylaxis should be undertaken in consultation with a transfusion medicine physician. Because there is very poor correlation between IgA deficiency and anaphylactic reactions, prophylactic use of washed RBCs in patients with IgA deficiency without a history of prior anaphylaxis is not recommended.
  2. Metabolic Complications of Blood Transfusions
    1. Potassium (K+) concentration changes are common with rapid blood transfusion but seldom of clinical importance. Although red cells leak K+ into the extracellular storage fluid during storage, red cells rapidly take back the K+ after transfusion. Large-volume transfusion results in recipient hypokalemia.
    2. Calcium (Ca2+) is bound by citrate, which is present in excess concentration as the anticoagulant in stored blood products. Rapid transfusion causes direct citrate infusion. Citrate is metabolized in all mitochondria and is excreted unchanged in the urine. Rapid infusion of citrate by transfusion may bind blood Ca2+ and decrease the ionized calcium level. Because citrate in blood components partitions with the plasma, plasma transfusions given rapidly are more likely than are pRBCs to induce citrate toxicity in the recipient. Severe hypocalcemia, manifested as tetany in the patient who is not anesthetized, hypotension, QT-segment prolongation on the electrocardiogram, and narrowed pulse pressure may occur. Citrate toxicity only occurs in rapid transfusion and is exacerbated by hypothermia, hyperkalemia, and impaired hepatic or renal perfusion. Ionized calcium levels should be monitored during rapid transfusions and aggressively repleted before development of signs or symptoms of severe hypocalcemia.
    3. Acid-base status: Although banked blood is acidic because of the metabolic effects of storage, the clinical effect on the patient is minimal. Citrate metabolism following transfusion induces a metabolic alkalosis. Acidosis in the setting of ongoing transfusion is more likely due to hypoperfusion and recipient lactic acidosis and will improve with volume resuscitation and tissue oxygenation.
    4. Other analytes: Blood storage solutions are hypernatremic and hyperglycemic. Transient disturbance of Na+ and glucose can be seen after large-volume transfusion. There is no evidence that the ammonia content of stored blood is of any clinical consequence. The level of free Hgb in RBCs due to storage hemolysis is less than 1%. Routine stored blood transfusions do not result in elevation of bilirubin or lactate dehydrogenase (LDH) or depression of haptoglobin in normal recipients.
  3. Infectious Complications of blood transfusions have been markedly reduced because of improved testing of donated blood. Recent changes to U.S. blood bank screening for viral pathogens include addition of specific nucleic acid testing of small pooled donated samples to enhance detection of hepatitis C virus (HCV) and HIV before serologic antibody conversion has occurred. Pooled products (eg, cryoprecipitate) have an increased risk of infection proportional to the number of donors.
    1. Hepatitis B: The current risk of HBV transmission is estimated to be 1 in 220 000 units transfused. Although the majority of infections are asymptomatic (only 35% of infected individuals demonstrate acute disease), approximately 1% to 10% become chronically infected with potentially significant long-term morbidity.
    2. Hepatitis C: The risk of transfusion-related HCV is approximately 1 in 1 935 000 units. Risks of HCV infection are more serious than those with HBV, however, because 85% of patients suffer chronic infection, 20% develop cirrhosis, and 1% to 5% of infections cause hepatocellular carcinoma.
    3. HIV: Because of improved screening and testing, the risk of transfusion- associated HIV has been estimated to be approximately 1 in 2.1 million units transfused in the United States.
    4. Cytomegalovirus (CMV): The prevalence of antibodies to CMV in the general population is approximately 70% by adulthood. The incidence of transfusion-associated CMV infection in patients who are previously uninfected is quite low following the use of leukoreduced blood.
    5. West Nile virus is a seasonal epidemic causing febrile and neurologic illnesses including meningoencephalitis and acute flaccid paralysis. Transfusion transmission was first documented in 2002 and blood donors are routinely screened for infection. The current risk in these areas is estimated at 1 in 1 million units transfused.
    6. Bacterial infections: Exclusion of donors with evidence of infectious disease and the storage of blood at 4 °C reduces the risk of transmitted bacterial infection. However, the necessity of room-temperature storage of platelets to maintain functional integrity creates a favorable medium for bacterial growth. Infection rates for platelets are estimated at 1 in 1000 to 2000 units and rates of septic reactions are on the order of 1 in 100 000 platelet doses transfused. Organisms likely to infect platelet concentrates include Staphylococcus aureus, coagulase-negative Staphylococcus, and diphtheroids. All platelet products are now screened for bacterial contamination during storage. RBCs are much less likely to become contaminated with bacteria, but the most commonly cultured organism is Yersinia enterocolitica, and the mortality rate from transfusion-acquired sepsis is approximately 60%.
  4. Transfusion-Related Acute Lung Injury (TRALI) is a syndrome of acute lung injury (see Chapter 19) after blood product transfusion. Symptoms may include severe hypoxemia, dyspnea, frothy sputum, and noncardiogenic pulmonary edema, sometimes accompanied by fever and hypotension, and usually occurring 4 to 6 hours after transfusion. The pathophysiology is incompletely understood but includes recipient exposure to HLA or granulocyte antibodies present in donor plasma. Mild forms are likely to go underrecognized.

    5. The incidence of TRALI has decreased over the past several years largely due to reduction in collections from multiparous donors and screening other at-risk donors for HLA antibodies. Any transfused product that contains plasma may cause TRALI. Mortality from TRALI is approximately 5%. Treatment is similar to that of other forms of acute lung injury and frequently requires mechanical ventilation. Most patients show dramatic clinical improvement within 48 hours and radiographic clearing of edema within a few days.

  5. Transfusion-Associated Circulatory Overload (TACO) is the most common serious noninfectious hazard of transfusion. TACO is associated with transfusion of multiple units of blood, older recipients, renal impairment, and cardiopulmonary disease. TACO commonly is associated with hypertension, tachypnea, venous engorgement, and signs of right or left heart volume overload.