At a Glance

All pregnant women should be tested for red cell alloantibodies. Detection of a clinically significant alloantibody may put the fetus at risk for hemolytic disease of the newborn (HDN). Predelivery antibody titers, as well as the paternal phenotype can help predict risk to the fetus. Fetal anemia may be detected by obstetric testing, such as amniocentesis for bilirubin levels and ultrasound. Although not typically severe, ABO incompatibility can also lead to HDN (most often A or B infants with O mothers). At birth, an anemic baby with jaundice may have HDN.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

ABO typing and a direct antiglobulin test (direct antiglobulin test [DAT], direct Coombs test) should be performed on a sample from the neonate. A cord blood sample is adequate. If positive and if testing has not already been performed, the mother should have a type and screen. If an alloantibody is detected, the baby should be phenotyped for that antigen. The baby will be antigen positive in the setting of HDN. The severity of the hemolysis can be determined by measuring the bilirubin. As bilirubin is a breakdown product of hemoglobin, hemolysis will raise levels. Indirect hyperbilirubinemia is typically seen in HDN (See Table 1).

Table 1
Direct antiglobulin test (DAT) Bilrubin, indirect Antibody Screen (mother) Antigen phenotype
positive for IgG elevated positive for alloantibody positive for antigen

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Other causes of indirect hyperbilirubinemia in the neonate should be ruled out.

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In the setting of ABO incompatibility, the DAT may only be weakly positive.

In cases of HDN to low-frequency antigens, the DAT may be positive but the antibody screen performed on the mother or neonate may be negative. In these cases, reactivity can be demonstrated by taking plasma or serum from the mother and demonstrating reactivity with the father’s red cells.

Not all infants with a positive DAT consistent with an alloantibody from the mother have hemolysis. Clinical correlation is necessary.

What Lab Results Are Absolutely Confirmatory?

No test is absolutely confirmatory. Although an eluate made from the infant’s red blood cells can confirm the identity of the antibody causing hemolysis, diagnosis is generally made without need for this test.