Beta-Thalassemia Intermedia Complicated by Autoimmune Hemolytic Anemia.

We present a case of β-thalassemia intermedia complicated by autoimmune hemolytic anemia after blood transfusion. The patient, a 24-year-old male of Italian descent with a previous diagnosis of β-thalassemia trait, presented with massive splenomegaly (27 cm) and microcytic anemia. At presentation, hemoglobin (Hgb) was 78 g/L (140–180 g/L), mean red cell volume was 78.3 fl (82.0–100.0 fl), and serum ferritin was 786 μg/L (23.9–366.0 μg/L); HbF was 100% by electrophoresis. Molecular studies confirmed homozygosity for the Sicilian δ/β thalassemia mutation. The direct anti-globulin test (DAT) and antibody screen prior to blood transfusion (blood group O, Rh -) were negative. The patient received two units of PRBC [(O, Rh -, phenotypically matched for Rh and Kell antigens (C-, E-, K-)]. Nineteen days later, the patient was febrile and the Hgb was 46 g/L with a positive DAT with both IgG and C3, and non-specific cold autoantibodies in the serum. Bacterial cultures and viral serology, including for parvovirus B19, were negative and the patient remained febrile despite broad-spectrum antibiotics. Over the next 15 days, 27 units of PRBC were given without improvement in his Hgb (range of 37–58 g/L) or reticulocyte count [range of 52–73 x10⁹/L (23–120 x 10⁹/L)]. Serum markers of red cell hemolysis were elevated with an LDH of 871 – 1473 U/L (110 U/L - 210 U/L) and a total bilirubin of 37.5 – 84.5 μmol/L (1.7 – 18.9 μmol/L). A bone marrow biopsy showed a hypercellular marrow (~ 95%) with marked erythroid hyperplasia, moderate left shift of the erythroid series and large areas of infiltration by histiocytes. Red cell serological testing evolved with the development of a strong non-specific warm autoantibody in the serum and eluate. Despite treatment with prednisone, IV IgG and erythropoietin, the Hgb and reticulocyte counts remained low. Urgent splenectomy led to resolution of the fever and some improvement in Hgb and reticulocyte count although he remained anemic (mean Hgb 55 g/L) with biochemical and serological evidence of ongoing hemolysis despite cessation of blood transfusions. On examination, the splenectomy specimen weighed 3900 g and revealed marked expansion of the red pulp and foci of histiocytes. Neither marrow nor splenic histiocytes contained acid-fast bacilli, and their presence was consistent with a reaction to the severe hemolysis. To treat the autoimmune hemolytic anemia, prednisone (100 mg/day tapered over 20 weeks) and Rituximab (375 mg/m², four weekly doses) were begun 15 days post-operatively. The Hgb and reticulocyte count improved rapidly with resolution of hemolysis, peaking at 134 g/L and 72 x 10⁹/L, respectively, although the last DAT remained positive. The patient now feels well. This case illustrates

1. autoimmune hemolytic anemia, arising post blood transfusion in a patient with thalassemia intermedia, the hemolysis resolving completely with immunotherapy (prednisone and Rituximab);

2. an unusually prominent infiltration of marrow and spleen with Gaucher-like histiocytes.