Autoimmune haemolytic anaemias

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs (RBCs originating from outside the person themselves, e.g. in the case of a blood transfusion). AIHA is a relatively rare condition, affecting one to three people per 100,000 per year. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus. Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs (RBCs originating from outside the person themselves, e.g. in the case of a blood transfusion). AIHA is a relatively rare condition, affecting one to three people per 100,000 per year. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus. The terminology used in this disease is somewhat ambiguous. Although MeSH uses the term 'autoimmune hemolytic anemia', some sources prefer the term 'immunohemolytic anemia' so drug reactions can be included in this category. The National Cancer Institute considers 'immunohemolytic anemia', 'autoimmune hemolytic anemia', and 'immune complex hemolytic anemia' to all be synonyms. Spherocytes are found in immunologically-mediated hemolytic anemias. The causes of AIHA are poorly understood. The disease may be primary, or secondary to another underlying illness. The primary illness is idiopathic (the two terms used synonymously). Idiopathic AIHA accounts for approximately 50% of cases. Secondary AIHA can result from many other illnesses. Warm and cold type AIHA each have their own more common secondary causes. The most common causes of secondary warm-type AIHA include lymphoproliferative disorders (e.g., chronic lymphocytic leukemia, lymphoma) and other autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Crohn's disease, ulcerative colitis). Less common causes of warm-type AIHA include neoplasms other than lymphoid, and infection. Secondary cold type AIHA is also caused primarily by lymphoproliferative disorders, but is also commonly caused by infection, especially by mycoplasma, viral pneumonia, infectious mononucleosis, and other respiratory infections. Less commonly, it can be caused by concomitant autoimmune disorders. Drug-induced AIHA, though rare, can be caused by a number of drugs, including α-methyldopa and penicillin. This is a type II immune response in which the drug binds to macromolecules on the surface of the RBCs and acts as an antigen. Antibodies are produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a, activate granular leukocytes (e.g., neutrophils), while other components of the system (C6, C7, C8, C9) either can form the membrane attack complex (MAC) or can bind the antibody, aiding phagocytosis by macrophages (C3b). This is one type of 'penicillin allergy'. In about half of cases, the cause of autoimmune hemolytic anemia cannot be determined (idiopathic or primary). This condition can also be caused by or occur with another disorder (secondary) or rarely, occur following the use of certain drugs (such as penicillin) or after a person has a blood and marrow stem cell transplant. Secondary causes of autoimmune hemolytic anemia include: AIHA can be caused by a number of different classes of antibody, with IgG and IgM antibodies being the main causative classes. Depending on which is involved, the pathology will differ. IgG is not very effective at activating complement and effectively binds the Fc receptor (FcR) of phagocytic cells, AIHA involving IgG is generally characterized by phagocytosis of RBCs. IgM is a potent activator of the classical complement pathway, thus, AIHA involving IgM is characterized by complement mediated lysis of RBCs. IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA). In general, IgG AIHA takes place in the spleen, whereas IgM AIHA takes place in Kupffer cells – phagocytic cells of the liver. Phagocytic AIHA is termed extravascular, whereas complement-mediated lysis of RBCs is termed intravascular AIHA. In order for intravascular AIHA to be recognizable, it requires overwhelming complement activation, therefore most AIHA is extravascular – be it IgG- or IgM-mediated.