Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients.

The clinical outcome, response to treatment, and occurrence of acute complications, were retrospectively investigated in 308 primary autoimmune hemolytic anemia (AIHA) cases and were correlated with serological characteristics and severity of anemia at onset. Patients had been followed-up for a median of 33 months (range 12-372); 60% were warm AIHA, 27% cold hemagglutinin disease, 8% mixed, and 5% atypical (mostly DAT-negative). The latter two categories showed more frequently a severe onset (Hb levels ≤6 g/dL) along with reticulocytopenia. The majority of warm AIHA received first line steroid therapy only, whereas patients with mixed and atypical forms were more frequently treated with 2 or more therapy lines, including splenectomy, immunosuppressants and rituximab. The cumulative incidence of relapse was increased in more severe cases (HR 3.08, 95% CI 1.44-6.57 for Hb ≤6 g/dL, p<0.001). Thrombotic events were associated to Hb levels ≤6 g/dL at onset, intravascular hemolysis and previous splenectomy. Predictors of a fatal outcome were severe infections particularly in splenectomized cases, acute renal failure, Evans' syndrome and multi-treatment (4 or more lines). The identification of severe and potentially fatal AIHA in a largely heterogeneous disease requires particular experienced attention by clinicians.