Figure 150-4 Coombs or direct antiglobulin test (DAT). In the DAT, so-called Coombs serum that recognizes human immunoglobulin (Ig) or complement (C) is used to detect the presence of antibody or C on the surface of the red blood cells (RBCs) by agglutination. A, An IgM antibody can bind two RBCs simultaneously because of its multiple antigen-binding sites. The great size of the IgM allows it to bridge the surface repulsive forces (zeta potential) between RBCs and cause agglutination. B, An IgG antibody is too small to bridge the zeta potential and cause agglutination. C, On the addition of Coombs serum, the zeta potential is bridged successfully, and RBCs agglutinate. (Modified from Ware RE, Rosse WF: Autoimmune hemolytic anemia. In Orkin SH, Nathan DG, Look AT, Ginsburg D, editors: Hematology of Infancy and Childhood, ed 6,
Philadelphia, 2003, Saunders, p 530.)
Hemolytic Anemia Caused by Disorders Extrinsic to the Red Blood Cell Etiology and Clinical Manifestations
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Isoimmune hemolysis is caused by active maternal immunization against fetal antigens that the mother’s erythrocytes do not express (see Chapter 62). Examples are antibodies to the A, B, and Rh D antigens; other Rh antigens; and the Kell, Duffy, and other blood groups. Anti-A and anti-B hemolysis is caused by the placental transfer of naturally occurring maternal antibodies from mothers who lack A or B antigen (usually blood type O). Positive results of the direct antiglobulin (Coombs) test on the infant’s RBCs (Fig. 150-4), the indirect antiglobulin test on the mother’s serum, and the presence of spherocytes and immature erythroid precursors (erythroblastosis) on the infant’s blood smear confirm this diagnosis. Isoimmune hemolytic disease varies in clinical severity. There may be no clinical manifestations, or the infant may exhibit jaundice, severe anemia, and hydrops fetalis.
Autoimmune hemolytic anemia is usually an acute, self-limited process that develops after an infection (Mycoplasma,Epstein-Barr, or other viral infections). Autoimmune hemolyticanemia may also be the presenting symptom of a chronic autoimmune disease (systemic lupus erythematosus, lymphoproliferative disorders, or immunodeficiency). Drugs may induce aCoombs-positive hemolytic anemia by forming a hapten on theRBC membrane (penicillin) or by forming immune complexes(quinidine) that attach to the RBC membrane. Antibodies thenactivate complement-induced intravascular hemolysis. Thethird type of drug-induced immune hemolysis occurs duringtreatment with α-methyldopa and a few other drugs. In this type,prolonged drug exposure alters the RBC membrane, inducingneoantigen formation. Antibodies are produced that bind to theneoantigen; this produces a positive antiglobulin test result farmore commonly than it actually induces hemolysis. In each ofthese conditions, the erythrocyte is an innocent bystander.