LAUSR

Pathophysiology Hemolytic anemia refers to the decreased survival of red blood cells (RBCs) related to intrinsic abnormalities (intracorpuscular) or extrinsic factors (extracorpuscular). Intracorpuscular hemolysis is mainly due to inherited RBC disorders and can be triggered by several factors, such as hypoxia, fever, or oxidant stress, whereas extracorpuscular hemolysis is generally an acquired condition of immune, toxic, or mechanical origin [1]. AH may be either intraor extravascular, thereby leading to distinct clinical presentations. In intravascular AH, RBCs burst predominantly within the vessels and release hemoglobin into the plasma. This leads to hemoglobinuria and potentially to acute kidney injury. Intravascular AH can occur in various situations, including infections (malaria, sepsis), mechanical heart valve prosthesis, thrombotic microangiopathies (TMAs), and alloimmunization. Conversely, in extravascular AH, illustrated by warm auto-antibody-mediated AH, the hemolysis is mediated by macrophages and antibodydependent cell cytotoxicity. This occurs primarily in the extravascular compartment within the reticulo-endothelial system (mainly the spleen and liver). In this setting, auto-antibodies target different RBC antigens (glycophorin, P-antigen, Rhesus, band 3) without complement activation, leading to warm autoimmune hemolytic anemia (AIHA). AIHA can be primary or secondary to Bor T-cell malignancies, autoimmune diseases, or primary immune deficiencies. Warm AIHA (wAIHA) is distinguishable from cold AIHA (cAIHA) based on the best temperature for allowing the detection of antibody binding activity. Cold antibodies are identified in cold agglutinin disease (CAD), which refers to the presence of monoclonal immunoglobulin M (IgM) antibodies secondary to a latent or overt lymphoplasmacytic proliferation. These antibodies target I or i antigens, agglutinate, and then trigger complement-dependent hemolysis. The agglutination is best observed at 4 °C in vitro, but hemolysis and agglutination occur at higher temperatures in vivo. The immune mechanism involved in RBC destruction needs to identified in order that the appropriate treatment be initiated [2–4].