Delayed hemolytic transfusion reaction

Did You Know?

• Anti-Jk antibodies were responsible for 13 of 44 cases of DHTR reported in the UK during 2021.
• Delayed blood transfusion reactions occur at an incidence of about 1/500 to 1/10,000 transfusions in the United States.
• The subacute presentation, milder symptoms and paucity of reporting data make determination of the true incidence difficult.

Mechanism

In immune-mediated DHTR, the recipient has antibodies that react with antigens on incompatible donor red blood cells, leading to lysis by immune cells such as macrophages. Severity depends on the type and quantity of antigens and antibodies, and the ability of antibodies to activate complement or opsonization. Some recipients develop higher antibody levels after immune stimulation by transfused cells. Hemolysis may be intravascular, where antibodies bind and activate complement while red blood cells are still in circulation, or extravascular, where opsonized cells are sequestered and phagocytosed by macrophages. Macrophage activation can increase cytokine production, causing systemic symptoms like fever, chills, abdominal pain, and back pain. Common blood group systems involved include ABO, Rh, Duffy, Kell, Kidd, and Lewis. For example, a person without a Kidd antigen (e.g., Jka-Jkb+) who forms anti-Jka antibody may have a DHTR upon subsequent transfusion with Jka-positive red blood cells. Antibodies against Kidd antigens can be difficult to detect due to molecular variability and weak in vitro expression.

Diagnosis

Diagnosis of DHTR is based on a positive elution test showing alloantibodies on transfused red blood cells or newly identified red blood cell alloantibodies in recipient serum. Antibody elution removes antibodies from red blood cell surfaces using heat, ultrasound, acids, or organic solvents; the eluted antibodies are then tested against a panel of reagent red blood cells of known phenotype. Additional criteria include an inadequate rise in post-transfusion hemoglobin, a rapid fall in hemoglobin to pre-transfusion levels, or unexplained appearance of spherocytes. A newly identified alloantibody demonstrated between 24 hours and 28 days after transfusion, with incomplete laboratory evidence, may also support diagnosis. Symptoms include drop in hemoglobin, fever, jaundice, hemoglobinuria, and elevated bilirubin and LDH. The direct antiglobulin test (direct Coombs test) detects antibodies already bound to red blood cells, while the indirect test detects free antibodies in serum; both are useful in investigating suspected transfusion reactions. Hyperhemolysis, which involves lysis of the recipient's own red blood cells in addition to donor cells, is distinct from DHTR.