With regards to CAD, the disease is typically characterized by cold-reactive IgM autoantibodies of monoclonal origin that function as hexamers, and an associated anemia that has been considered for decades to be due to the clearance of IgM and CP derived C3 fragment-bound cells by complement receptors in the reticuloendothelial system in a process designated extravascular hemolysis (Shi et al., 2014). This evidence concerns the gene CD40LG and cold agglutinin disease.