LAUSR

BACKGROUND Approximately 5%-10% of autoimmune hemolytic anemia (AIHA) cases are negative for direct antiglobulin test (DAT). We previously reported a classification system for untreated patients with DAT-negative AIHA by quantifying levels of red blood cell (RBC)-bound IgG. This study investigated the clinical utility of a novel diagnostic algorithm with a comprehensive classification system and characterized each subgroup in DAT-negative AIHA. STUDY DESIGN AND METHODS We assessed 637 patients with undiagnosed hemolytic anemia using our diagnostic algorithm and classification system, which was based on RBC-bound IgG levels and results of column method-DAT before and after washing RBCs. RESULTS Patients were diagnosed with DAT-negative AIHA with 97% sensitivity and 84% specificity when the laboratory tests were performed before treatment and classified into the following six categories: tube DAT-negative, low-affinity IgG, double DAT-negative, IgA- or IgM-positive, low-affinity IgM, and s/o non-AIHA. The first three types were major conditions and accounted for 76% of DAT-negative AIHA cases. Based on multivariate analyses of idiopathic DAT-negative AIHA (n = 71), platelet count and albumin concentration were significant factors for survival at 1-year follow-up. The low-affinity IgG group showed the highest platelet count and albumin levels, better response to steroids, and higher 1-year survival rate than those in other groups. DISCUSSION Our classification included DAT-negative, IgA-driven, and warm-IgM AIHA categories, which were atypical forms of AIHA with the severe onset and increased risk of relapse. When treating a patient with DAT-negative hemolysis, atypical AIHA should be considered and tested in reference laboratories, especially before treatment.