Diagnostic challenges in DAT-negative autoimmune haemolytic anaemia

Autoimmune haemolytic anaemia (AIHA) is a rare, heterogeneous condition that poses diagnostic challenges, especially in direct antiglobulin test (DAT)-negative cases, where the absence of detectable autoantibodies complicates diagnosis. We report a case of a male patient in his late 60s diagnosed with a rare subtype of IgA-mediated, DAT-negative AIHA. The patient presented with painless jaundice, pruritus and laboratory evidence of haemolysis, including anaemia, reticulocytosis, elevated unconjugated bilirubin, increased lactate dehydrogenase and decreased haptoglobins. Initial and repeated standard DATs were negative. Subsequent testing ruled out viral, autoimmune and malignancy-related causes. An extended DAT using alternative reagents for IgA and IgM confirmed an IgA-mediated AIHA. Further investigations later confirmed the diagnosis of an indolent lymphoproliferative disorder following detection of a clonal B-cell population in the peripheral blood. This case underscores the diagnostic complexity of AIHA and the value of a comprehensive diagnostic approach to finding cases of rare DAT-negative subtypes.