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Harrison’s Manual of Medicine



Transfusion Reactions

Immunologically Mediated Reactions

Nonimmune Reactions

DEFINITION   A life-threatening systemic hypersensitivity reaction to contact with an allergen; it may appear within minutes of exposure to the offending substance. Manifestations include respiratory distress; pruritus; urticaria; mucous membrane swelling; gastrointestinal disturbances including nausea, vomiting, pain, and diarrhea; and vascular collapse. Virtually any allergen may incite an anaphylactic reaction, but among the more common agents are proteins such as antisera, hormones, pollen extracts, Hymenoptera venom, foods; drugs (especially antibiotics); and diagnostic agents. Atopy does not seem to predispose to anaphylaxis from penicillin or venom exposures.
CLINICAL PRESENTATION   Time to onset is variable, but symptoms usually occur within seconds to minutes of exposure to the offending antigen:

Respiratory: mucous membrane swelling, hoarseness, stridor, wheezing

Cardiovascular: tachycardia, hypotension

Cutaneous: pruritus, urticaria, angioedema
DIAGNOSIS   Made by obtaining history of exposure to offending substance with subsequent development of characteristic complex of Sx.

Mild symptoms such as pruritus and urticaria can be controlled by administration of 0.2 to 0.5 mL of 1:1000 epinephrine solution SC, repeated at 20- min intervals as necessary.
An IV infusion should be initiated. Hypotension should be treated by IV administration of 2.5 mL of 1:10,000 epinephrine solution at 5- to 10-min intervals, volume expanders, e.g., as normal saline, and vasopressor agents, e.g., dopamine, if intractable hypotension occurs.
Epinephrine provides both a- and b-adrenergic effects, resulting in vasoconstriction and bronchial smooth-muscle relaxation. Beta blockers are relatively contraindicated in persons at risk for anaphylactic reactions.
The following should also be used as necessary:

Antihistamines such as diphenhydramine 50 to 100 mg IM or IV

Aminophylline 0.25 to 0.5 g IV for bronchospasm


Glucocorticoids—IV; not useful for acute manifestations but may help control persistent hypotension or bronchospasm

PREVENTION   Avoidance of offending antigen, where possible; skin testing and desensitization to materials such as penicillin and Hymenoptera venom, if necessary. Individuals should wear an informational bracelet and have immediate access to an unexpired epinephrine kit.
Transfusion reactions may be classified as immune or nonimmune.
Immunologically Mediated Reactions
Reaction may be directed against red or white blood cells, platelets, or IgA; in addition, other, less well-characterized reactions may occur.
1.   Acute hemolytic transfusion reactions: Usually due to ABO incompatibility, although alloantibodies directed against other antigens may result in intravascular hemolysis; very rapid and massive hemolysis occurs. Sx may include restlessness, anxiety, flushing, chest or back pain, tachypnea, tachycardia, nausea, shock, renal failure, coagulation disorders (including DIC).
2.   Delayed hemolytic transfusion reactions: Occur in pts previously sensitized to RBC alloantigens who have a negative alloantibody screen due to low antibody levels. When the pt is transfused an anamnestic alloantibody response occurs, leading to extravascular hemolysis of the transfused RBCs.
3.   Allergic reactions: Characterized by a pruritic rash, edema, headache, and dizziness. Related to plasma proteins found in transfused components.
4.   Anaphylactic reactions: Severe reactions characterized by hypotension, difficulty breathing, bronchospasm, respiratory arrest, shock. Patients with IgA deficiency are at particular risk for severe reaction due to sensitization to IgA.
5.   Transfusion-related acute lung injury: Rare reaction that results from transfusion of donor plasma that contains high titer anti-HLA antibodies that bind to corresponding antigens on recipient leukocytes. Recipient develops respiratory compromise and signs of noncardiogenic pulmonary edema. Treatment is supportive; most pts recover without sequelae.
6.   Graft-versus-host disease (GVH): Rare complication of transfusion mediated by donor T lymphocytes that recognize host HLA antigens as foreign and mount an immune response. Can occur when blood components that contain viable T lymphocytes are transfused into immunodeficient recipients or into immunocompetent recipients who share HLA antigens with the donor. Clinically, characterized by pancytopenia, cutaneous eruption, diarrhea, and liver function abnormalities. Transfusion GVH is notoriously resistant to treatment with immunosuppressive medications and is usually fatal. Transfusion-related GVH can be prevented by irradiation of cellular components before transfusion into pts at risk.
Laboratory Investigation of Immune-Mediated Reactions

Careful check on identity of donor and recipient; samples of recipient blood to blood bank for analysis and further cross-matching

Documentation of hemolysis—plasma and urine hemoglobin, haptoglobin, hematocrit, bilirubin

Check renal status—urinalysis, BUN, creatinine

Check coagulation status—platelet count, PT, PTT


Avoid further transfusion unless absolutely necessary

Management of shock and renal failure in intravascular hemolysis; osmotic diuresis and volume expansion may be indicated in certain cases; if renal failure ensues, adjust drug doses and closely monitor fluid/electrolyte status

Factor replacement if needed to control coagulation abnormalities; platelet infusion if thrombocytopenia severe

Nonimmune Reactions
1.   Circulatory overload: Especially in infants and pts with renal or cardiac insufficiency. Effects of massive transfusion include hyperkalemia, ammonia and citrate toxicity, dilutional coagulopathy, thrombocytopenia.
2.   Transmission of infection: Hepatitis, syphilis, CMV, malaria, babesiosis, toxoplasmosis, brucellosis, and HIV can all be transmitted by transfused blood.
3.   Iron overload: With repeated transfusions; may require chelation therapy.

For a more detailed discussion, see Austen KF: Allergies, Anaphylaxis, and Systemic Mastocytosis, Chap. 310, p. 1913; and Dzieczkowski JS, Anderson KC: Transfusion Biology and Therapy, Chap. 114, p. 733, in HPIM-15.

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