Clinical Review

Autoimmune Hemolytic Anemia: Evaluation and Diagnosis

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Transfusion Therapy

Performing transfusions can be very difficult in patients with AIHA.2 The presence of the autoantibody can interfere with typing of the blood and almost always interferes with the crossmatch, since this final step consists of mixing the patient’s serum or plasma with donor red cells. In most patients with AIHA, the autoantibodies will react with any donor cells, rendering a negative crossmatch impossible. Without the crossmatch, the concern is that underlying alloantibodies can be missed. Studies indicate that 15% to 32% of patients will have underlying alloantibodies, which can lead to transfusion reactions.2 However, there are 2 considerations that may mitigate these concerns.11,12 First, patients who have never been transfused or pregnant will rarely have alloantibodies. Second, a patient who has been transfused in the remote past may have an anamnestic antibody response but not an immediate hemolytic reaction.

The transfusion service can take several steps to identify alloantibodies. Occasionally, if the autoantibody is weakly reacting when the patient’s serum is tested against a panel of reagent red cells, the alloantibodies can be identified by their stronger reactions as compared with the weakly reactive autoantibody. The most common technique for identifying alloantibodies is the autoadsorption technique.4,13 This involves incu-bating the patient’s red cells with the patient’s serum to adsorb the autoantibody. After a period of incubation, the cells are pelleted and the serum is collected as the supernatant. The adsorbed serum may be incubated with another sample of the patient’s cells for a second adsorption if the initial agglutination reactions of the patient’s serum with the reagent cells were strong. After 1 to 3 adsorptions, the adsorbed serum is tested with a red cell panel in order to check for “leftover” alloantibodies.

When a patient is first suspected of having AIHA, a generous sample of blood should be given to the transfusion service to allow for adequate testing. Many centers will test the blood not only for blood groups ABO and D but also perform full Rh typing plus check for Kidd, Duffy and Kell status.14 Increasingly, this is performed by direct genetic sequencing for the appropriate genotypes. This can allow transfusion of phenotypically matched red blood cells to lessen the risk of alloantibody formation.

One difficult issue is timing of transfusion. Clinicians are often hesitant to transfuse patients with AIHA due to fear of reactions, but in patients with severe anemia, especially elderly patients or those with heart disease, transfusion can be lifesaving. Since in some cases it may take hours to screen for alloantibodies, it is often preferable to transfuse patients with severe anemia and observe carefully for reaction.


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