9/L (10-90), bilirubin 1.5 mg/dL (0-1.0), lactate dehydrogenase 1715 U/L (normal < 210) and ferritin 697 ng/mL. The blood film showed microcytosis and coarse basophilic stippling consistent with β-thalassemia trait. Only very occasional spherocytes were noted and there was no agglutination. A bone marrow biopsy revealed mild erythroid hyperplasia and otherwise unremarkable morphology. The direct antiglobulin test (DAT) was repeatedly negative for IgG but weakly positive for C3d. Special DAT assays by gel method, cold saline wash and IgM/IgA substrates, were negative. Weak red cell autoantibodies were detectable eventually by polyethylene glycol (PEG) method through a reticulocyte enriched blood specimen, aiming to increase the sensitivity of the DAT assay by reducing the contamination of more aged transfused red cells. Weak red cell autoantibodies with no demonstrable specificity were also detected in the patient’s serum by PEG. An AHA with IgG autoantibody directed against reticulocytes or a mature RBC precursor was suspected based upon the reticulocytopenia and IgG positive DAT restricted to the reticulocyte enriched RBC fraction. 2 Prednisone 1.5 mg/kg/day, i.v. cyclophos phamide (~900 mg/m 2 monthly for five doses) and ritux imab (1,000 mg/m 2 for two doses) were administered with subsequent cessation of transfusion requirements and return to her baseline hemoglobin of 10.5 g/dL. AHA with atypical features, as illustrated above, raises challenges in diagnosis and management. Anemia can be multifactorial and peripheral blood morphology with coexisting conditions such as thalassemia trait 3 may be misleading. Importantly, 5-10% of patients with AHA are “DAT-negative”. A laboratory approach to such cases has been suggested but definitive proof of autoimmune hemolysis is often difficult to establish. 4