Cryopathic Hemolytic Anemias

Autoimmune hemolytic anemia (AHA) is characterized by the presence of autoantibodies directed against autologous red blood cells (RBCs), leading to a shortened RBC survival. The presence of an autoantibody and/or complement on RBC membranes detected by positive direct antiglobulin test (DAT) is essential for the diagnosis. Most patients with AHA exhibit warm-reactive antibodies usually of the IgG immunoglobulin isotype, whereas the majority of the remaining AHAs demonstrate cold-reactive antibodies. These autoantibodies bind to RBCs at temperatures below 37 °C, usually below 31 °C, thus triggering a cascade of immune responses resulting in the destruction of RBCs. These types of AHA, termed cryopathic hemolytic anemias, are uncommon, at least in the classic form. Approximately, 7–25% of AHAs are cold agglutinin mediated. The incidence of cold agglutinin disease is approximately 1 in 300,000 patients. Reports demonstrate a slight predilection for female patients who are 60 years of age and older, peaking in the seventh and eighth decades of life. In this chapter, we will discuss the pathogenesis, diagnosis, prognosis, and management of these cryopathic hemolytic anemias.