The diagnosis depends on the detection of antibodies and/or complement on red cells. This is done with the direct Coombs test, in which the patient’s red cells are incubated with antibodies against human immunoglobulin or complement. In a positive test result, these antibodies cause the patient’s red cells to clump (agglutinate). The indirect Coombs test, which assesses the ability of the patient’s serum to agglutinate test red cells bearing defined surface determinants, can then be used to characterize the target of the antibody.
In this entity, hemolysis results from the binding of high-affinity autoantibodies to red cells, which are then removed from the circulation by phagocytes in the
Table 12.4 Classification of Immunohemolytic Anemias
Secondary:Bcellneoplasms(e.g.,chroniclymphocyticleukemia),autoimmunedisorders(e.g.,systemiclupuserythematosus),drugs(e.g.,α-methyldopa,penicillin,quinidine)
Acute: Mycoplasma infection,infectiousmononucleosis
Chronic:idiopathic,Bcelllymphoidneoplasms(e.g.,lymphoplasmacyticlymphoma) spleen and elsewhere. In addition to frank erythrophagocytosis, incomplete consumption (“nibbling”) of antibody-coated red cells by macrophages removes membrane and transforms red cells into spherocytes, which are rapidly destroyed in the spleen, just as in hereditary spherocytosis (described earlier). Warm antibody immunohemolytic anemia is caused by immunoglobulin G (IgG) or (rarely) IgA antibodies that are active at 37°C. More than 60% of cases are idiopathic (primary), whereas another 25% are secondary to an underlying immunologic disorder (e.g., systemic lupus erythematosus) or are induced by drugs. The clinical severity is variable, but most patients have chronic mild anemia and moderate splenomegaly and require no treatment.
The mechanisms of hemolysis induced by drugs are varied and in some instances poorly understood. Drugs such as α-methyldopa induce autoantibodies against intrinsic red cell constituents, in particular Rh blood group antigens. Presumably, the drug somehow alters the immunogenicity of native epitopes and thereby circumvents T cell tolerance (Chapter 5). Other drugs such as penicillin act as haptens, which induce an antibody response by binding covalently to red cell membrane proteins. Sometimes antibodies recognize a drug in the circulation and form immune complexes that are deposited on red cells. Here they may fix complement or act as opsonins, either of which can lead to hemolysis.