Autoimmune hemolytic anemia (AIHA) is an autoimmune disorder which 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 circulation (anemia).
[1][2] 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.
[9] Symptoms of AIHA may be due to the underlying anemia; including shortness of breath or dyspnea, fatigue, headache, muscle weakness and pallor.
[10] In cold agglutinin disease (cold antibody type), agglutination and impaired passage of red blood cells through capillaries in the extremities causes acrocyanosis and Raynaud phenomenon with a rare complication of gangrene[4] Spherocytes are found in immunologically mediated hemolytic anemias.
[11] Signs of hemolysis that are present in AIHA include low hemoglobin (blood count), alterations in levels of cell markers of hemolysis; including elevated lactate dehydrogenase (LDH), decreased haptoglobin and elevated unconjugated bilirubin.
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.
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).
[citation needed] In about half of cases, the cause of autoimmune hemolytic anemia cannot be determined (idiopathic or primary).
IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA).
Patients with cold-type AIHA, therefore, have higher disease activity when body temperature falls into a hypothermic state.
Warm-type AIHA shows a positive reaction with antisera to IgG antibodies with or without complement activation.
Following confirmation of hemolysis (seen with laboratory markers of low hemoglobin, elevated LDH, decreased haptoglobin, and elevated unconjugated bilirubin), a direct antiglobulin test (DAT)(also known as a Coomb's test) is done to show auto-immune pathogenesis with antibodies, complement or both on the erythrocyte surface.
Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA.
[4] Other third line options, that are less studied, include azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil and bortezomib.
[4] In warm AIHA; cross-matching of blood will show incompatibility so it is recommended to perform a bedside in vivo compatibility test prior to infusion.
[4] "Blood-induced icterus" produced by the release of massive amounts of a coloring material from blood cells followed by the formation of bile was recognized and described by Vanlair and Voltaire Masius' in 1871.
About 20 years later, Hayem distinguished between congenital hemolytic anemia and an acquired type of infectious icterus associated with chronic splenomegaly.
French investigators led by Chauffard stressed the importance of red-cell autoagglutination in patients with acquired hemolytic anemia.
[citation needed] During the past three decades, studies defining red-cell blood groups and serum antibodies have produced diagnostic methods that have laid the basis for immunologic concepts relevant to many of the acquired hemolytic states.
Of these developments, the antiglobulin test described by Coombs, Mourant, and Race in 1945 has proved to be one of the more important, useful tools now available for the detection of immune hemolytic states.
[citation needed] A hemolytic state exists whenever the red cell survival time is shortened from the normal average of 120 days.