Cold Agglutinin Disease: Improved Understanding of Pathogenesis Helps Define Targets for Therapy

The last 2 decades have seen great progress in understanding the pathogenesis of cold agglutinin disease (CAD) and development effective therapies. Cold agglutinins can cause hemolytic anemia as well peripheral circulatory symptoms such acrocyanosis. We distinguish CAD, a well-defined clinicopathologic entity, from secondary syndrome. This review addresses histopathologic, immune phenotypic, molecular features that allow CAD to be classified distinct clonal lymphoproliferative disorder bone marrow, recently recognized WHO classification. discuss recent data on possible overlap or distinction between Waldenström’s macroglobulinemia. Two major steps are identified: B-cell lymphoproliferation (leading monoclonal IgM production) complement-mediated hemolysis. Each these constitutes target for treatment. Established novel experimental therapies reviewed.