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Delayed Hemolytic Transfusion Reactions
Delayed hemolytic transfusion reactions (DHTRs) typically occur 3–10 days after red blood cell (RBC) transfusion that appear to be serologically compatible. These reactions occur in patients who have been alloimmunized to minor RBC antigens during previous transfusions and/or pregnancies; pretransfusion testing fails to detect these alloantibodies due to their low titer. After reexposure to antigen-positive RBCs, an anamnestic response occurs, with rapid rise in antibody titer. Decreased survival of transfused RBCs may result, primarily due to extravascular hemolysis. In the majority of cases, however, anamnestic antibody production does not cause detectable hemolysis. The term delayed serologic transfusion reaction (DSTR) defines reactions in which anamnestic antibody is identified serologically, with absence of clinical evidence of accelerated RBC destruction. Antigens implicated most often in DHTRs and DSTRs are in the Kidd, Duffy, Kell, and MNS systems, in order of decreasing frequency.
Incidence
In combination, DHTRs and DSTRs occur in approximately 1 in 1500 transfusions, with DSTRs occurring up to four times more often than DHTRs. Data from Mayo Clinic calculated an incidence rate of 1:6944 patients transfused for DHTR and 1:3146 patients transfused for DSTR using gel technique and 1:1200 patients transfused for DHTR and 1:611 patients transfused for DSTR using PEG technique. Antibodies to E, Fy(a), and Jk(a) were most frequently identified.
Clinical Manifestations
DHTRs are characterized clinically by an unexpected drop in hemoglobin or less than expected posttransfusion increment in hemoglobin ( Table 64.1 ). This diagnosis should be considered days to weeks after transfusion, although hemolysis may be more prolonged. Symptoms of extravascular hemolysis include fever, chills, jaundice, malaise, back pain and, uncommonly, renal failure. Symptoms may mimic vasoocclusive pain crisis in patients with sickle cell disease (SCD), and thus the underlying diagnosis of DHTR is often missed.
Table 64.1
Timeline of Delayed Hemolytic Transfusion Reaction
Modified from Hillyer, C. D., Silberstein, L. E., Ness, P. M., Anderson, K. C., Roback, J. D. (Eds.), (2007). Blood banking and transfusion medicine: Basic principles & practice, (2nd ed.). Philadelphia: Elsevier.
| Time (Days) | Event | Explanation |
|---|---|---|
| 0 | Pretransfusion antibody screening negative | Antibody titer below detectable levels |
| 1 | RBC transfusion | |
| 3–10 | Clinical signs of hemolysis may appear | Accelerated destruction of transfused donor RBCs |
| 10–21 | Posttransfusion sample: positive direct antiglobulin (DAT) and positive antibody screen due to newly detected antibody | Antibody titer increases |
| >21 | DAT may become negative | Antibody-sensitized donor RBCs removed from circulation |
| 21–300 | DAT may persist as positive; eluates may reveal alloantibody specificity or panagglutination | Alloantibody binding nonspecifically to autologous RBC, or development of a warm autoantibody |
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