Clinical Pathology: General Principles, Hematology & Coagulation, Transfusion Medicine

• ABO and Rh typing and antibody screen/antibody identification are performed at the first prenatal visit.

• Antibodies to antigens in the Rh, Kell, and Duffy systems are the most common causes of hemolytic disease of the fetus and newborn (HDFN); however, there are many reports of other IgG antibodies causing HDFN.

• If a clinically significant antibody is identified, paternal expression should be determined.

• Serologic testing should be performed first to determine whether the father expresses the antigen and whether he is homozygous or heterozygous. Fetal tissue may be obtained via chronionic villus sampling, amniocentesis, or cordocentesis for molecular typing.

• The maternal antibody titer should be determined during the first trimester, if possible, to establish a baseline.

• For anti-D, the critical titer is 16 or 32 at antihuman globulin phase. If the titer is less than or equal to 8, maternal samples should be drawn every 4 to 6 weeks to determine the antibody titer. Often, previous frozen maternal samples are run simultaneously with new samples to account for differences in technique between technologists. A twofold increase in the titer is considered clinically significant.

• A titer of 16 or 32 is considered clinically significant for most other antigens as well. However, Kell antigens are expressed on erythropoietic precursor cells and HDFN due to Kell antibodies can suppress erythropoiesis. A titer of 8 is generally considered clinically significant for antibodies directed against antigens in the Kell system.

• If the mother has a clinically significant titer, the fetus may be monitored with middle cerebral artery Dopplers. An increase in cardiac output due to fetal anemia will be detected as an increase in middle cerebral artery peak blood flow velocity.

• Fetal samples may be drawn via cordocentesis for direct measurement of the hemoglobin and hematocrit, and intrauterine transfusions may be provided. Red blood cells for intrauterine transfusion should be irradiated, leukoreduced or cytomegalovirus negative, hemoglobin S negative, and lack the offending antigen(s).

• Prior to the use of middle cerebral artery Dopplers, the clinical status of the fetus would be monitored by amniocentesis for mothers with critical titers. The change in the optical density (OD) of the amniotic fluid is proportional to the bilirubin concentration. The optical densities would be plotted on a graph (Liley’s system) of OD versus weeks of gestation to determine the severity of disease.



 
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