Hemolytic disease of the fetus and newborn (HDFN) caused by the Rh blood group system can go undetected due to a rare diagnostic challenge known as the “blocked D phenomenon,” according to a case report published recently in The Turkish Journal of Pediatrics.
This condition was seen in a set of twins born to a RhD-negative mother and initially misidentified as RhD-negative themselves. Misdiagnosis delayed the recognition of HDFN and complicated early management. The twins were ultimately found to be RhD-positive after undergoing specialized testing, highlighting the importance of advanced techniques in identifying immune-mediated hemolysis in newborns.
HDFN results when maternal antibodies attack the baby’s red blood cells, leading to anemia and jaundice. In this case, a 35-year-old woman gave birth to twins via cesarean section at 38 weeks. The infants were vigorous dichorionic diamniotic twins, meaning each twin had its own chorionic and amniotic sacs.
The mother, who was B RhD-negative, had not received proper antibody screening during pregnancy. Her husband’s blood group was O RhD-positive. Although the babies initially appeared healthy, both were diagnosed with severe jaundice and anemia within the first 24 hours of life.
Read more about HDFN causes and risk factors
“The possibility of the blocking phenomenon should be considered while interpreting blood group results from fetal or neonatal samples in an alloimmunized pregnancy with potent antibodies,” the study authors wrote. “A false-negative RhD grouping can occur if maternal IgG antibodies saturate all available antigen sites on fetal red blood cells, preventing the anti-D reagent from binding.”
Blood tests revealed high levels of bilirubin and anemia in both twins, requiring immediate double-volume exchange transfusions and phototherapy. The mother’s blood showed high titers of anti-D antibodies. Surprisingly, initial Rh typing showed the babies as RhD-negative, inconsistent with the suspected diagnosis. The discrepancy raised suspicion of the blocked D phenomenon—a rare situation in which maternal anti-D antibodies coat fetal red cells so densely that standard tests cannot detect the D antigen.
Further testing involved gentle heat elution of the newborns’ red cells, allowing for accurate re-typing with monoclonal IgM anti-D reagents. The results confirmed both infants were actually RhD-positive. At a 6-month follow-up, both twins were correctly phenotyped as O RhD-positive. This case adds to 12 known reports of blocked D and emphasizes the diagnostic importance of using antiglobulin tests, such as the direct and indirect Coombs tests, in Rh-incompatible pregnancies.
For patients, this means that even when a baby’s RhD typing appears negative, HDFN may still be present if the mother has Rh antibodies. Early detection can allow for timely interventions such as exchange transfusions, intravenous immunoglobulin and blood transfusions, preventing long-term damage.
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