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...
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Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss (Part 14) 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 commonform of acquired hemolytic anemia. In fact, not quite appropriately, the twophrases 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 redcells. Once a red cell is coated by antibody, it will be destroyed by one or moremechanisms. In most cases the Fc portion of the antibody will be recognized bythe Fc receptor of macrophages, and this will trigger erythrophagocytosis (Fig.101-7). Thus, destruction of red cells will take place wherever macrophages areabundant—i.e., in the spleen, liver, and bone marrow. Because of the specialanatomy 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 spleenand liver, and it is therefore called extravascular hemolysis. In some cases thenature of the antibody is such (usually an IgM antibody) that the antigen-antibodycomplex 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 bedestroyed directly, known as intravascular hemolysis. Figure 101-7 Mechanism of antibody-mediated immune destruction of red cells.(From N Young et al: Clinical Hematology. Copyright Elsevier, 2006; withpermission.) Clinical Features The onset of AIHA is very often abrupt and can be dramatic. Thehemoglobin level can drop, within days, to as low as 4 g/dL; the massive red cellremoval will produce jaundice, and often the spleen will be enlarged. When thistriad is present, the suspicion of AIHA must be high. When hemolysis is (in part)intravascular, the telltale sign will be hemoglobinuria, which the patient mayreport or for which the physician must test. The diagnostic test for AIHA is theantiglobulin test worked out in 1945 by R.R.A. Coombs and known since by hisname. The beauty of this test is that it directly detects the pathogenetic mediator ofthe disease, i.e., the presence of antibody on the red cells themselves. When thetest is positive, it clinches the diagnosis; when it is negative, the diagnosis isunlikely. However, the sensitivity of the Coombs test varies depending on thetechnology that is used, and in doubtful cases a repeat in a specialized lab isadvisable; the term Coombs-negative AIHA is a last resort. In some cases theautoantibody 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 withvirtually all types of red cells. As in autoimmune diseases in general, the real cause of AIHA remainsobscure. However, from the clinical point of view, an important feature is thatAIHA can appear to be isolated, or it can develop as part of a more generalautoimmune disease, particularly systemic lupus erythematosus (SLE), of whichsometimes it may be the first manifestation. Therefore, when AIHA is diagnosed,a full screen for autoimmune disease is imperative. In some cases AIHA can beassociated, on first presentation or subsequently, with autoimmunethrombocytopenia (Evanss syndrome). Autoimmune Hemolytic Anemia: Treatment The first-line treatment of AIHA is glucocorticoids. A dose of prednisoneof 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. Forpatients who do not respond, and for those who have relapsed, second-linetreatment measures include long-term immunosuppression with low-doseprednisone, azathioprine, or cyclosporine. In patients whose AIHA has becomechronic, and sometimes even earlier, splenectomy is a viable option: although itdoes not cure the disease, it can produce significant benefit by removing a majorsite of hemolysis, thus improving the anemia and/or reducing the need forimmunosuppressive 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 severerefractory cases, either auto- or allohematopoietic stem cell transplantation hasbeen used, sometimes successfully.