Transfusion reactions

Transfusion reactions

1. Acute hemolytic transfusion reactions most commonly occur when ABO-incompatible blood is transfused, resulting in recipient anti-A and/or anti-B antibodies attaching to donor RBC antigens and forming antigen-antibody complexes. These antigen-antibody complexes activate complement, precipitating intravascular hemolysis with the release of RBC stroma and free Hb. Immune system activation also results in endothelial and mast cell activation, stimulating the release of serotonin, histamine, and bradykinin; these mediators set off a cascade of widespread vasodilation, diffuse inflammation, and acute hypotension. The net results may include shock, kidney injury due to Hb precipitation in renal tubules, and DIC (see Section IX.B). Many signs and symptoms of an acute hemolytic transfusion reaction appear immediately and include fever, chest pain, anxiety, back pain, and dyspnea. Many are masked by general anesthesia, but intraoperative clues to the diagnosis include fever, hypotension, hemoglobinuria, unexplained bleeding, or failure of the Hct to increase after transfusion. Table 36.3 outlines steps to take if a transfusion reaction is suspected. The incidence of fatal hemolytic transfusion reactions in the United States is approximately 1 in every 250,000 to 1,000,000 units transfused. Most reactions occur because of administrative errors, with the majority caused by improper identification of the blood unit or patient. The importance of adhering to strict policies of checking blood and matching to the correct patient in the operating room cannot be overemphasized.
2. Delayed hemolytic transfusion reactions occur because of antibodies targeting minor RBC antigens (eg, Kidd) and are characterized by extravascular hemolysis. Delayed hemolytic transfusions reactions are most common in patients with a history of multiple prior transfusions, especially those with chronic anemias or hemoglobinopathies. These reactions often present days to weeks after transfusion. Patients may experience minimal symptoms but may display signs of anemia and jaundice. Laboratory studies reveal a positive direct antiglobulin test, hyperbilirubinemia, decreased haptoglobin levels, and hemosiderin in the urine. Treatment is aimed at correcting the anemia.
3. Febrile nonhemolytic transfusion reactions (FNHTRs) are the most common transfusion reactions, occurring in approximately 1% of RBC transfusions and up to 30% of platelet transfusions. These may occur in response to cytokines in the stored product or may occur when anti-leukocyte or anti-HLA antibodies in the recipient react with donor white blood cells or platelets in the transfused blood product, thus producing pyrogen and proinflammatory cytokine release. Signs and symptoms include fever, chills, rigors, tachycardia, malaise, nausea, and vomiting. Approach to treatment involves first stopping the transfusion and excluding an acute hemolytic transfusion reaction or bacterial contamination of the donor unit. Acetaminophen and meperidine may diminish fever and rigors, respectively. Once the diagnosis of FNHTR has been made, future reactions may be avoided or diminished by administering leukoreduced blood products (see Section IV.B.2), premedicating at-risk patients with acetaminophen and hydrocortisone (50-100 mg IV), and administering the transfusion slowly.
4. Allergic transfusion reactions are common, occurring in 1% to 3% of transfusions. They arise from recipient IgE-mediated antibody responses to donor plasma proteins. Urticaria with pruritus and erythema is the most common manifestation, but bronchospasm or anaphylaxis may occur in rare instances. Many patients also develop fevers. Patients with IgA deficiency may be at an increased risk of allergic transfusion reactions and anaphylaxis because of the presence of anti-IgA antibodies that react with transfused IgA; this is best prevented by administering plasma-free blood products (eg, washed PRBCs) to patients with known IgA deficiency. Treatment involves stopping the transfusion, excluding more severe reactions (see above), and administering antihistamines (eg, diphenhydramine 50 mg IV and ranitidine 50 mg IV). A significant reaction may warrant administration of a corticosteroid (methylprednisolone 80 mg IV). Bronchospasm and anaphylaxis should be treated as described in Chapter 17.
5. TRALI is a condition involving rapid-onset respiratory insufficiency following blood, FFP, cryoprecipitate, or platelet transfusion. Signs and symptoms include fevers, dyspnea, hypoxemia, hypotension, and low-pressure pulmonary edema developing within 4 hours of transfusion. TRALI is thought to occur when anti-HLA and anti-leukocyte antibodies present in donor plasma target recipient neutrophils, which damage the lung parenchyma. This mechanism also accounts for the transient leukopenia that may be observed in recipients who develop TRALI. TRALI may rapidly progress to hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS) and is currently the leading cause of transfusion-related mortality in the United States. Most cases are traced to plasma-containing blood products from multiparous female donors who have developed anti-HLA antibodies; therefore, measures to prevent plasma donation by women who have been pregnant may reduce the incidence of TRALI-related episodes.
6. Transfusion-associated circulatory overload (TACO) is a condition of circulatory congestion secondary to the fluid volumes administered during massive transfusion. Symptoms often mimic those of decompensated congestive heart failure and include dyspnea, high-pressure pulmonary edema, tachycardia, and jugular venous distention. While TRALI usually produces pulmonary edema in the absence of overt hypervolemia, signs of hypervolemia and increased left ventricular filling pressures may be observed in TACO. TACO often affects patients at risk for congestive heart failure and occurs in less than 1% of transfusions. If a patient is at risk for fluid overload with high-volume transfusion, diuretics or volume-reduced blood products may be administered prophylactically. However, as TACO is often traced to overly aggressive transfusion in patients with preexisting myocardial dysfunction, the clinician should also be judicious with respect to the volume transfused.
7. GVHD is a rare and serious complication of blood transfusion resulting from an attack of immunocompetent donor lymphocytes on the host’s tissues. In a great majority of transfusions, donor lymphocytes are destroyed by the recipient’s immune system, thus preventing GVHD. However, if the host is immunodeficient or if a specific type of partial donor-recipient HLA matching occurs, the risk of GVHD is increased. The condition often develops 4 to 30 days after transfusion, with patients typically presenting with fever and an erythematous rash that may become generalized. Other symptoms include anorexia, vomiting, abdominal pain, and cough. The diagnosis is made by skin biopsy and confirmed by demonstrating the presence of circulating lymphocytes with a different HLA phenotype, verifying their origin from the donor. GVHD is poorly responsive to most available treatments. Therefore, prevention is of utmost importance and is achieved by exposing lymphocyte-containing components to gamma radiation, thereby inactivating donor lymphocytes. In addition to immunocompromised recipients, patients receiving blood products from family donors or HLA-matched platelets are viable candidates for transfusion of irradiated blood components owing to an associated risk of partial HLA matching.