French protocol for the diagnosis and management of autoimmune hemolytic anemia in adults

Autoimmune hemolytic anaemias (AIHAs) represent different subtypes of a rare autoimmune disease in which autoantibodies targeting autoantigens expressed on autologous red blood cells' (RBCs) membrane are produced, leading to their accelerated destruction. In the presence of hemolytic anaemia, the direct antiglobulin test (DAT) is the cornerstone of AIHA diagnosis. AIHAs are classified according to the isotype and the thermal optimum of the autoantibody, into warm (wAIHAs), cold and mixed AIHAs. wAIHAs, by far the most frequent type of AIHAs, are associated with underlying conditions in ∼50% of cases. Among adults, cold AIHAs include cold agglutinin disease (CAD), and cold agglutinin syndrome (CAS) when there is an underlying condition. Both CAD and CAS are IgM cold-antibody driven AIHAs characterized by classical complement pathway-mediated hemolysis. The management of AIHAs which has has long been empirical is mostly based on corticosteroids±rituximab for wAIHAs and on rituximab±bendamustine for CAD requiring to be treated, complement inhibition with sutimlimab being a new therapeutic option for CAD. This article reporting the French guidelines focused on diagnosis and treatment of adult AIHAs is adapted from the last update of the Protocole National de Diagnostic et de Soins (French protocol for diagnosis and management). These guidelines have been set up and led by the French national center for adult' immune cytopenias (CeReCAI).