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

SUMMARY. 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 hyperbili‐rubinaemia, 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.