The majority of cases of hemolytic disease of the fetus and newborn (HDFN) are due to RhD, Kell, or ABO antigen incompatibility. However, a rare case of HDFN due to C antigen incompatibility was recently published in the Southeast Asian Journal of Case Report and Review.
The case involved a newborn delivered at 37 weeks of gestation after an uncomplicated pregnancy. However, he was admitted to the neonatal intensive care unit (NICU) due to a positive Coombs test suggestive of red blood cell destruction, also known as hemolysis.
At the time of admission, the patient had an unremarkable physical exam, without the typical pallor of jaundice, and his vital signs were normal. Laboratory tests, however, revealed elevated bilirubin levels—a hallmark of HDFN.
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Due to findings suggestive of HDFN, the physicians performed several antibody tests to rule out HDFN caused by minor antigens. The results showed that the mother was negative for the C antigen, while the father was positive.
The patient’s condition continued to worsen despite receiving a blood transfusion and intensive phototherapy. After receiving two doses of intravenous immunoglobulin, the patient exhibited marked improvement in both hemoglobin and bilirubin levels.
After several weeks of treatment, the symptoms and laboratory parameters continued to improve, and the baby was discharged. He is currently healthy and does not appear to have any long-term symptoms.
The role of minor blood group incompatibility in HDFN
Minor blood group incompatibility involving antigens such as C, c, E, e, Fy, and Jk is responsible for approximately 3.5% of all HDFN cases. In many instances, HDFN caused by minor blood group incompatibilities is misdiagnosed, so the actual incidence may be higher.
“When a newborn presents with signs of hemolysis, such as a positive direct agglutination test and hyperbilirubinemia, and no Rh or ABO incompatibility is identified, it may indicate the possibility of a minor blood group incompatibility,” the authors wrote.
The clinical severity of minor blood group incompatibility can vary. Many patients are asymptomatic or present with very mild symptoms, while others may exhibit severe hemolysis and hyperbilirubinemia.
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