Hemolytic transfusion reactions can be defined as acute or delayed. Both are the result of recipient antibody and complement attack on donor cells. The target and concentration of recipient antibodies differentiates acute from delayed hemolytic transfusion reactions. In contrast to acute hemolytic transfusion reactions which are almost always due to ABO incompatibility, delayed hemolytic transfusion reactions (DHTRs) are typically secondary to antibodies associated with the Rh and Kidd systems (or other “minor” antigens). Patients who have delayed reactions also typically have lower initial antibody concentrations than patients who have acute reactions; the initial antibody concentration in patients with DHTRs is usually too low to be detected by laboratory tests.
DHTRs occur in 0.2-2.6% of patients receiving transfusions. The most common manifestation of DHTR is a decrease in post-transfusion hematocrit due to mild, gradual hemolysis. Rarely, patients present with jaundice, hemoglobinuria, and acute kidney injury.
The onset of DHTR is 24 hours to 21 days and is determined by the presence of prior alloimmunization. When alloimmunization is de novo, hemolysis may occur several weeks after the exposure. More commonly, when alloimmunization has already occurred because of prior transfusions or pregnancy, hemolysis may occur within hours or a few days following reexposure to the same antigen (anamnestic response).
In the postoperative patient with a decreasing hematocrit (≥24 hours post-transfusion), DHTR should be on the differential along with acute or subacute blood loss. Laboratory evidence of DHTR includes spherocytes on blood smear, reticulocytosis, increased LDH, and increased unconjugated bilirubin. Direct antiglobulin test (DAT) and antibody screen should be repeated on any patient who is suspected of having DHTR, although DAT may be negative if all transfused red cells have been eliminated from the circulation. No specific management is indicated for DHTR other than adequate hydration and monitoring of hematocrit and renal function.