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Obesity is a Risk Factor for Rh D Alloimmunization

RhD hemolytic disease of the fetus and newborn is caused by maternal immunization to the D antigen, followed by subsequent transfer of maternal IgG across the placenta resulting in immune hemolysis of fetal red blood cells. Rhesus immune globulin (RhIg) is a concentrated solution of IgG anti-D derived from human plasma that was developed to prevent immunization of Rh-negative women to the D antigen and thereby prevent hemolytic disease of the fetus and newborn caused by anti-D. It was licensed in the United States in 1968 and since that time the incidence of Rh D alloimmunization has dramatically decreased from 16% to 0.1%. In spite of this success, new cases of anti-D sensitization continue to occur. Two recent Letters to the Editor of the Archives of Pathology and Laboratory Medicine suggest that obesity may be an unrecognized risk factor for D sensitization.

In the first article, Pham et al. explained that dosing of RhIg is based on the Nadler formula, which includes height and weight to calculate maternal blood volume. If these measurements are not known, the College of American Pathologists RhIg dose calculator recommends using an assumed maternal total blood volume of 5000 mL.

During the past 20 years, there has been a dramatic increase in the prevalence of obesity in the United States. Today, it is estimated that 34.9% of the adults in the United States are obese. Pregnant women may weigh more than 100 kg and their total blood volume may exceed 6000 mL. Therefore, many patients may have a total blood volume that exceeds 5000 mL. Underestimation of maternal total blood volume and consequent underdosing of RhIG increase the risk of developing D alloimmunization and severe hemolytic disease of the fetus and newborn in future pregnancies.

In a subsequent Letter to the Editor, Woo et al. expressed concern that the route of administration of RhIg to obese patients may also be a contributing factor. A thick layer of adipose tissue increases the chance that RhIg will be injected into the subcutaneous tissue instead of muscle, resulting in a subtherapeutic dose. These authors point out that the package insert for Rhophylac includes a statement that intravenous administration should be considered if reaching the muscle is a concern.

To further reduce the incidence of D alloimmunization, physicians need to accurately calculate the total blood volume of obese patients and administer RhIg intravenously using a product such as Rhophylac or WinRho.

Pham HP, Marques MB and Williams LA, Rhesus Immune Globulin Dosing in the Obesity Epidemic Era. Arch Pathol Lab Med 2015;139:1084.

Woo EJ and Kaushal M. Rhesus Immunoglobulin Dosage and Administration in Obese Individuals. Arch Pathol Lab Med 2017;141:17.

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