Blood Transfusion Reactions

Patients on blood transfusion are monitored to detect the development of the following reactions that may occur in response to blood transfusion.

The reactions may be immediate reactions or delayed reactions.

1. Hemolytic Reactions:

Transfusion of ABO incompatible blood cause immediate hemolysis and can even lead to the death of the recipient. Incompatibility due to other blood groups are usually less severe, however, deaths have been reported.

The most common immediate presentation of an incompatible blood transfusion is fever with chills. Chest pain, hypotension, nausea, flushing, dyspnoea, loin pain, and hemoglobin urea are the other signs and symptoms.

The hemolytic transfusion reaction may progress to shock, disseminated intravascular coagulation, renal failure, and death. Delayed hemolytic transfusion reactions may occur 3 to 10 days after transfusion or it may pass off undetected clinically. It occurs in a recipient who has antibodies against donor RBC antigens (such as Kidd, Duffy, and Kell blood group antigens), which were not detected during pretransfusion screening tests.

The recipient develops fever, anemia, and jaundice. Blood sample is taken from such recipient and a DAT is performed. A positive DAT indicates the presence of transfused RBCs coated with antibodies. In the laboratory, the antibodies coating the RBCs are eluted and tested against a panel of reagent erythrocytes by indirect Coombs’ agglutination (IAT) procedure. The IAT procedure is done to identify the nature of RBC antigens against which the transfusion reaction occurred.

2. Febrile Non-Hemolytic Transfusion Reactions (FNHTR):

Earlier it was thought that the FNHTR in a blood transfused patient was due to a reaction between recipient antibodies with donor leukocytes. Hence leukocyte filters were introduced. (Blood from the blood bag is allowed to pass through a leukocyte filter so that only RBCs and plasma reached the recipient.)

In spite of the introduction of leukocyte filters, the recipients still developed FNHTR. It is also observed that during storage of blood the leukocytes release cytokines such as IL-lβ, IL-6, and TNFa. These cytokines are known to have pyrogenic effect i.e. fever inducing effect; .

Now it is suggested that these cytokines may be responsible for FNHTR. The clinician should distinguish the cause of fever in a blood transfused patient, which may be due to (a) an associated hemolytic transfusion reaction, (b) bacterial contamination of the blood, or (c) due to FNHTR.

3. Blood transfusion related acute lung injury:

High titers of recipient leukocyte antibodies against donor leukocytes may cause pulmonary edema in the recipient. The leukocyte antibodies-donor leukocyte immune complexes deposit in the lung microvessels. Consequently, the complement system is activated leading to leukocytes accumulation in the lung microvasculature. The enzymes and free radicals released by the activated leukocytes are thought to cause lung injury.

The patient develops fever, dyspnoea, and marked hypoxemia. The acute respiratory distress occurs within 1 to 6 hours after transfusion and needs aggressive intensive care respiratory support. Most patients improve within 48 to 96 hours if treated promptly (Sometimes donor’s leukocyte antibodies may bind to recipient’s leukocytes and lead to pulmonary edema).

4. Allergic Reactions due to Blood Transfusion:

Allergic reactions due to blood transfusion are thought to be caused by the donor plasma proteins. The allergic reactions occur in 1 to 2 percent of blood transfusions. Patients with a previous history of allergy have a greater tendency to develop allergy after blood transfusion. The allergic recipient develops itching, hives, and local erythema, and rarely cardiopulmonary instability.

Mild allergic reactions are treated with antihistamines. If the recipient develops severe allergic reactions, washed RBCs may be transfused to the patient. One should take enough care in transfusing blood to IgA deficient patients. Anti-IgA antibodies in the circulation of IgA deficient patient react with the IgA in the transfused blood and leads to development of severe allergy and anaphylaxis.

Immunological Mechanisms of Blood Transfusion Reactions:

The recipient antibodies bind to donor RBC antigens and form immune complexes. The immune complexes activate the complement system and kinin system and result in the production of a number of cytokines.

i. Activation of Hageman factor (factor Xlla) results in the activation of kinin system. Activation of kinin system results in the production of bradykinin, which causes vasodilatation, increased vascular permeability, and hypotension.

ii. Immune complex activation of classical complement pathway leads to intravascular hemolysis. The C3a and C5a complement components formed during complement activation release mast cell inflammatory mediators.

iii. Hageman factor and free erythrocyte stroma (of the hemolysed RBCs) activate the intrinsic clotting cascade and result in development of disseminated intravascular coagulation (DIC).

iv. Systemic hypotension, vasoconstriction of renal vessels, and DIC lead to renal failure.

Transfusion-associated Graft Versus Host Disease (TA-GVHD):

In a blood transfused patient, if the donor lymphocytes engraft the bone marrow of the recipient and clonally expand the TA-GVHD occurs. In GVHD the donor lymphocytes recognize the recipient’s tissue as foreign and induce immune responses against the recipient’s tissues. GVHD is characterized by fever, skin rash, hepatitis, and diarrhea. The donor lymphocytes attack the recipient’s bone marrow and lead to significant aplasia. Most cases of TA-GVH respond poorly to treatment and result in death.

The following patients are at risk of developing TA-GVHD:

i. Patients transfused with HLA-matched platelets.

ii. Newborns undergoing exchange transfusion.

iii. T cell immunodeficiency patients.

iv. Severely immunosuppressed patients (due to drugs or radiotherapy, etc).

v. Fetuses receiving intrauterine transfusions.

Infections Transmissible Through Blood Transfusion:

Viruses, bacteria, and parasites in the donor blood lead to blood transfusion induced infections in the recipient.

Therefore, before use, the blood should be screened for the presence of microbes or antibodies against the microbes by standard tests:

i. Peripheral blood smear of the donor blood is screened for malarial parasites.

ii. The donor blood is screened for

a) Anti-HIV-1 and anti-HIV-2 by ELISA

b) HIV p24 by ELISA

c) Anti-HCV by ELISA

d) Anti-HBc by ELISA

e) HBsAg by ELISA

f) Anti-HTLV-1 and anti-HTLV-2 by ELISA

g) Antibodies to Treponema pallidum (the bacteria that causes syphilis).

About 50 percent of blood donors are infected with cytomegalovirus (CMV). In severely immunocompromised patients, CMV infection results in significant mortality and morbidity. If possible, anti-CMV (determined by ELISA) negative blood should be given to low- birth weight infants and CMV sero-negative pregnant women.

Other microorganisms and parasites transmissible by blood transfusion are gram-positive bacteria, gram- negative bacteria, Babesis microti, Tryponosoma cruzi, Wucherireria bancrofti, Loa loa, and other filarial parasites in blood.