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I. DEFINITION

Isoimmune hemolytic anemia may result when ABO incompatibility occurs between the mother and the newborn infant. This disorder is most common with blood type A or B infants born to type O mothers. The hemolytic process begins in utero and is the result of active placental transport of maternal isoantibody. In type O mothers, isoantibody is predominantly 7S-IgG (immunoglobulin G) and is capable of crossing the placental membranes. Because of its larger size, the mostly 19S-IgM (immunoglobulin M) isoantibody found in type A or type B mothers cannot cross. Symptomatic clinical disease, which usually does not present until after birth, is a compensated mild hemolytic anemia with reticulocytosis, microspherocytosis, and early-onset unconjugated hyperbilirubinemia.

II. INCIDENCE

Risk factors for ABO incompatibility are present in 12% to 15% of pregnancies, but evidence of fetal sensitization (positive direct Coombs test) occurs in only 3% to 4%. Symptomatic ABO hemolytic disease occurs in <1% of all newborn infants but accounts for approximately two-thirds of observed cases of hemolytic disease in the newborn.

III. PATHOPHYSIOLOGY

Transplacental transport of maternal isoantibody results in an immune reaction with the A or B antigen on fetal erythrocytes, which produces characteristic microspherocytes. This process eventually results in complete extravascular hemolysis of the end-stage spherocyte. The ongoing hemolysis is balanced by compensatory reticulocytosis and shortening of the cell cycle time, so that there is overall maintenance of the erythrocyte indices within physiologic limits. A paucity of A or B antigenic sites on the fetal (in contrast to the adult) erythrocytes and competitive binding of isoantibody to a myriad of other antigenic sites in other tissues may explain the often mild hemolytic process that occurs and the usual absence of progressive disease with subsequent pregnancies.

IV. RISK FACTORS

  1. A1 antigen in the infant. Of the major blood group antigens, the A1 antigen has the greatest antigenicity and is associated with the greater risk of symptomatic disease. However, the hemolytic activity of anti-B antibodies is higher than that of anti-A antibodies and may produce a more severe disease, in particular among infants of African American descent.

  2. Elevated isohemagglutinins. Antepartum intestinal parasitism or third-trimester immunization with tetanus toxoid or pneumococcal vaccine may stimulate isoantibody titer to A or B antigens.

  3. Maternal immune serum globulin anti-A/B titers. Anti-A/B titers >512% are significantly associated with the risk of ABO hemolytic disease of the newborn and may be an early indicator for therapy.

  4. Birth order. Birth order is not considered a risk factor. Maternal isoantibody exists naturally and is independent of prior exposure to incompatible fetal blood group antigens.

V. CLINICAL PRESENTATION

  1. Jaundice. Icterus is often the sole physical manifestation of ABO incompatibility with a clinically significant level of hemolysis. The onset is usually within the first 24 hours of life. The ...

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