Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss (Part 14) Autoimmune Hemolytic Anemia (AIHA) Except for countries where malaria is endemic, AIHA is the most common form of acquired hemolytic anemia. In fact, not quite appropriately, the two phrases are sometimes used synonymously. Pathophysiology AIHA is caused by an autoantibody directed against a red cell antigen, i.e., a molecule present on the surface of red cells. The autoantibody binds to the red cells. Once a red cell is coated by antibody, it will be destroyed by one or more mechanisms. In most cases the Fc portion of the antibody will be recognized by the Fc receptor of macrophages, and this will trigger erythrophagocytosis (Fig. 101-7). Thus, destruction of red cells will take place wherever macrophages are abundant—i.e., in the spleen, liver, and bone marrow. Because of the special anatomy of the spleen, this organ is particularly efficient in trapping antibody- coated red cells, and often this is the predominant site of red cell destruction. Although in severe cases even circulating monocytes can take part in this process, most of the phagocytosis-mediated red cell destruction takes place in the spleen and liver, and it is therefore called extravascular hemolysis. In some cases the nature of the antibody is such (usually an IgM antibody) that the antigen-antibody complex on the surface of red cells is able to activate complement (C). As a result, a large amount of membrane attack complex will form, and the red cells may be destroyed directly, known as intravascular hemolysis. Figure 101-7 Mechanism of antibody-mediated immune destruction of red cells. (From N Young et al: Clinical Hema tology. Copyright Elsevier, 2006; with permission.) Clinical Features The onset of AIHA is very often abrupt and can be dramatic. The hemoglobin level can drop, within days, to as low as 4 g/dL; the massive red cell removal will produce jaundice, and often the spleen will be enlarged. When this triad is present, the suspicion of AIHA must be high. When hemolysis is (in part) intravascular, the telltale sign will be hemoglobinuria, which the patient may report or for which the physician must test. The diagnostic test for AIHA is the antiglobulin test worked out in 1945 by R.R.A. Coombs and known since by his name. The beauty of this test is that it directly detects the pathogenetic mediator of the disease, i.e., the presence of antibody on the red cells themselves. When the test is positive, it clinches the diagnosis; when it is negative, the diagnosis is unlikely. However, the sensitivity of the Coombs test varies depending on the technology that is used, and in doubtful cases a repeat in a specialized lab is advisable; the term Coombs-negative AIHA is a last resort. In some cases the autoantibody has a defined identity: it may be specific for a Rhesus system antigen (often anti-e). In many cases it is regarded as "unspecific" because it reacts with virtually all types of red cells. As in autoimmune diseases in general, the real cause of AIHA remains obscure. However, from the clinical point of view, an important feature is that AIHA can appear to be isolated, or it can develop as part of a more general autoimmune disease, particularly systemic lupus erythematosus (SLE), of which sometimes it may be the first manifestation. Therefore, when AIHA is diagnosed, a full screen for autoimmune disease is imperative. In some cases AIHA can be associated, on first presentation or subsequently, with autoimmune thrombocytopenia (Evans's syndrome). Autoimmune Hemolytic Anemia: Treatment The first-line treatment of AIHA is glucocorticoids. A dose of prednisone of 1 mg/kg per day will cause a prompt remission in at least one-half of cases. Whereas some patients are apparently cured, relapses are not uncommon. For patients who do not respond, and for those who have relapsed, second-line treatment measures include long-term immunosuppression with low-dose prednisone, azathioprine, or cyclosporine. In patients whose AIHA has become chronic, and sometimes even earlier, splenectomy is a viable option: although it does not cure the disease, it can produce significant benefit by removing a major site of hemolysis, thus improving the anemia and/or reducing the need for immunosuppressive agents. Most of the management of AIHA is not evidence- based. However, the anti-CD20 antibody rituximab has produced responses. Anecdotal reports suggest response to intravenous immunoglobulin. In severe refractory cases, either auto- or allohematopoietic stem cell transplantation has been used, sometimes successfully. . Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss (Part 14) Autoimmune Hemolytic Anemia (AIHA) Except for countries where malaria. receptor of macrophages, and this will trigger erythrophagocytosis (Fig. 101- 7). Thus, destruction of red cells will take place wherever macrophages are abundant—i.e., in the spleen, liver, and. associated, on first presentation or subsequently, with autoimmune thrombocytopenia (Evans's syndrome). Autoimmune Hemolytic Anemia: Treatment The first-line treatment of AIHA is glucocorticoids.