Diagnostic and therapeutic challenges of severe Rh e-specific IgA-mediated autoimmune hemolytic anemia

Dear Editor, Autoimmune hemolytic anemia (AIHA) is usually easily diagnosed using general laboratory findings such as elevated lactate dehydrogenase, reticulocytosis, low serum haptoglobin levels, and a positive direct antiglobulin test (DAT) using antibodies directed against IgG and C3d complement. However, in about 14% of AIHA cases, only IgA antibodies are found, which are not detected by routine DAT [1]. We here present a case with a severe Rh e-specific IgA-mediated AIHA. A 26-year-old man presented at the emergency ward with icterus, red urine, fever, and complaints of profound malaise. Initial laboratory results showed a severe anemia with a hemoglobin concentration of 4.9 g/dL, with high mean corpuscular volume (MCV, 113 fl), 36 erythroblasts/ 100 white blood cells, spherocytes in the blood smear, and 15% reticulocytes (reference range 0.4–2%). Physical examination demonstrated hepatosplenomegaly. AIHA was suspected, and prednisone (1 mg/kg) was started. However, DAT was negative with anti-IgG and anti-complement reagent. Since the patient's Hb was decreasing even further, he was transfused with two erythrocyte concentrates (ECs) blood group O, ccdee. The presence of irregular antibodies was excluded, and his Rh genotype was determined to be CCDee. In the next 2 days, multiple causes for hemolytic anemia were excluded and the patient received another transfusion. DAT was repeated using anti-IgG, anticomplement, and, additionally, anti-IgA. The test with anti-IgA was strongly positive indicating a rare IgAmediated autoimmune hemolytic anemia. The IgA antibodies were eluted from the red blood cells (RBC) and were shown to be of the IgA class and were strong autoanti-e. This