A cold scare: Formation of cold reactive anti-A1 coinciding with gross hemolysis

Anti-A₁ antibodies can be found as a usually clinically insignificant naturally occurring cold IgM antibody in A-subgroup patients. It is known from multiple prior case reports that warm-reactive anti-A₁ that reacts at 37 °C can be clinically significant, and it has been previously reported that it could form after alloimmunization with donor A₁ red blood cell (RBC) transfusion. In addition, the development of anti-A₁, often as an autoantibody, have been described in the setting of various malignancies, perhaps due to expressed subtle alterations of the ABO antigens provoking an immune response. Here, we report a rare case of a cold-reactive anti-A₁ alloantibody (after multiple transfusions with group A₁ RBC units) in a 76 year old male patient (A₂) with history of myelodysplastic syndrome and metastatic carcinoma who presented with hemolytic anemia and dark urine. The patient had previously typed as blood type A without reverse typing reaction for anti-A₁; as a result, the patient had been transfused with group A₁ RBCs. Four days prior to discovery of the ABO discrepancy, the patient had a febrile transfusion reaction associated with his A₁ RBC transfusion. On admission, his immunohematology workup demonstrated an alloantibody to anti-A₁ that coincidentally appeared during a new onset of hemolytic anemia. Case reports of patients with hemolytic anemia with a newly developed anti-A₁ alloantibody are sparse in the literature, and this case is particularly interesting as the cold reactive anti-A₁ (without demonstrable wide thermal amplitude) appeared to form after alloimmunization and in the setting of an underlying malignancy.