Autoimmune hemolytic anemia: causes and consequences

Abstract

Introduction: Autoimmune hemolytic anemia (AIHA) is classified according to the direct antiglobulin test (DAT) and thermal characteristics of the autoantibody into warm and cold forms, and in primary versus secondary depending on the presence of associated conditions.

Areas covered: AIHA displays a multifactorial pathogenesis, including genetic (association with congenital conditions and certain mutations), environmental (drugs, infections, including SARS-CoV-2, pollution, etc.), and miscellaneous factors (solid/hematologic neoplasms, systemic autoimmune diseases, etc.) contributing to tolerance breakdown. Several mechanisms, such as autoantibody production, complement activation, monocyte/macrophage phagocytosis, and bone marrow compensation are implicated in extra-/intravascular hemolysis. Treatment should be differentiated and sequenced according to AIHA type (i.e. steroids followed by rituximab for warm, rituximab alone or in association with bendamustine or fludarabine for cold forms). Several new drugs targeting B-cells/plasma cells, complement, and phagocytosis are in clinical trials. Finally, thrombosis and infections may complicate disease course burdening quality of life and increasing mortality.

Expert opinion: Beyond warm and cold AIHA, a gray-zone still exists including mixed and DAT negative forms representing an unmet need. AIHA management is rapidly changing through an increasing knowledge of the pathogenic mechanisms, the refinement of diagnostic tools, and the development of novel targeted and combination therapies.

Keywords: Warm autoimmune hemolytic anemia; cold agglutinin disease; complement system; direct antiglobulin test; infection; monocyte/macrophage system; rituximab; thrombosis.