Three examples of Rh haemolytic disease of the newborn with a negative direct antiglobulin test

Transfus Med. 1995 Jun;5(2):113-6. doi: 10.1111/j.1365-3148.1995.tb00197.x.


Typically the serological diagnosis of alloimmune haemolytic disease of the newborn (HDN) includes a positive direct antiglobulin test on the infant's red cells, and the presence of an IgG red cell alloantibody in both maternal and cord sera. HDN with a negative direct antiglobulin test has been reported with anti-A and anti-B, but not with other red-cell alloantibodies. In this report we describe four examples of HDN in infants whose red cells had a negative direct antiglobulin test. The first case was diagnosed retrospectively when the infant was admitted to hospital aged 3 weeks with severe anaemia and cardiac failure, and subsequently died. Maternal and infant sera were both shown to contain anti-C: however, the direct antiglobulin test on the infant's red cells was negative. Approximately 1 year later the mother of this infant gave birth to triplets: soon after birth one of the triplets required an exchange transfusion, one had hyperbilirubinaemia, and the third was unaffected. Anti-C and anti-e were detectable in the maternal serum at this time. The most probable Rh genotypes of the two affected infants were R1R2 (CDe/cDE), while the Rh genotype of the unaffected infant was R2R2 (cDE/cDE). Anti-c was implicated as causing HDN in a fourth infant (from a different family) who was a hydropic stillborn. The direct antiglobulin test on fetal blood was negative and other causes of non-immune hydrops were excluded. These four infants provide evidence that the direct antiglobulin test may be negative in some severely affected and even fatal cases of HDN.

Publication types

  • Case Reports

MeSH terms

  • Coombs Test
  • Erythroblastosis, Fetal / diagnosis*
  • Erythroblastosis, Fetal / immunology
  • Erythroblastosis, Fetal / mortality
  • Erythrocytes / immunology*
  • False Negative Reactions
  • Female
  • Humans
  • Infant, Newborn
  • Pregnancy
  • Retrospective Studies
  • Rh-Hr Blood-Group System / immunology*


  • Rh-Hr Blood-Group System