Coombs Test Exceptions

There are some antibodies where an infant’s direct coombs can come back negative, but still be affected. These infants need to have either an antigen test done (to confirm baby cannot be affected by antibodies) or indirect coombs run (to tell if there are circulating antibodies in the plasma that haven’t bound yet). In rare cases, there are antibodies where mom's antibody test can come back negative, but baby still be affected.

Negative IAT on Mom - Still Affect Baby

Negative DAT on Baby - Still Affect Baby

anti Dia,
anti Jsa,
anti Wra
C
c
Fya
Good
H
Jra
M
Mta

Negative IAT on Mom But Still Affect Baby

Anti-Dia

Anti-Dia has been known to be undetectable on maternal indirect coombs test during pregnancy, yet still cause issues with the infant after birth. It leads to speculation if the other Diego blood group antibody, anti-Dib, would be similar. 

[Hemolytic disease of newborn infants caused by anti-Diego antibodies]. - 
Monestier M https://www.ncbi.nlm.nih.gov/pubmed/6542344
Characterization of an anti-Dia antibody causing hemolytic disease in a newborn infant - 
Authors L. M. Alves de Lima http://onlinelibrary.wiley.com/doi/10.1046/j.1537-2995.1982.22382224952.x/abstract

Anti-Jsa

The first case of hydrops from anti-Jsa was reported in 2005. What is startling to note about this was that the mother's Indirect Coombs test was NEGATIVE despite the infant having hydrops and a positive direct coombs (strength of 3+). The woman had lost an infant before due to hydrops, the cause of which was never identified. Further testing revealed the woman to be Jsa- and the baby Jsa+. Both maternal and fetal blood reacted with Jsa+ cells and they were able to identify the antibody as anti-Jsa. Delayed onset anemia was found on day 14 and the infant was treated with a transfusion, phototherapy and erythropoietin.
The first case of hydrops fetalis caused by anti-Jsa. - Alvaro Ringressi 
http://www.bloodtransfusion.it/articoli/000026/en/76-83.pdf

Anti-Wra

Like anti-Dia, anti-Wra has been known to be undetectable on maternal indirect coombs test during pregnancy, yet still cause issues with the infant after birth. It leads to speculation if the other Diego blood group antibody, anti-Dib, would be similar. 

[A case of hemolytic disease in a newborn associated with anti-Wra (WRIGHT) antibodies]. - 
Monestier M https://www.ncbi.nlm.nih.gov/pubmed/6463512
[Clinical case of the month. Mild hemolytic disease of the newborn due to an anti-Wr(a) antibody] - Keutgens A https://www.ncbi.nlm.nih.gov/pubmed/22984759

Negative DAT on Baby But Still Affected

Anti-C

“In newborns with hemolytic disease due to anti-c or anti-C antibodies, direct antibody test results may be negative, and the diagnosis is established after indirect Coombs testing.” http://emedicine.medscape.com/article/974349-workup?

Three examples of Rh haemolytic disease of the
newborn with a negative direct antiglobulin test.
Typically the serological diagnosis of alloimmune haemolytic disease of the newborn (HDN) includes a positive direct antiglobulin test on theinfant'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, thedirect 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. https://www.ncbi.nlm.nih.gov/pubmed/7655573

Anti-c

“In newborns with hemolytic disease due to anti-c or anti-C antibodies, direct antibody test results may be negative, and the diagnosis is established after indirect Coombs testing.” http://emedicine.medscape.com/article/974349-workup?

Three examples of Rh haemolytic disease of the
newborn with a negative direct antiglobulin test.
Typically the serological diagnosis of alloimmune haemolytic disease of the newborn (HDN) includes a positive direct antiglobulin test on theinfant'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, thedirect 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. https://www.ncbi.nlm.nih.gov/pubmed/7655573

Anti-Fya

Haemolytic disease of the newborn caused by anti-c, anti-E and anti-Fya antibodies: report of five cases - Author Agota Babinszki
http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0223(199906)19:6%3C533::AID-PD570%3E3.0.CO;2-5/full

Anti-Good

It is known that the direct coombs test may be negative with anti-Good and still cause severe HDN. 

The Good Factor as a possible cause of hemolytic disease of the newborn. - Abraham Frumin http://www.bloodjournal.org/content/bloodjournal/15/5/681.full.pdf?sso-checked=true

Anti-H

2013 saw the first recorded case of HDN due to anti-H in a Bombay phenotype mother. The infant had a negative direct coombs test, but signs of hemolysis. His bilirubin levels were high enough to warrant an exchange transfusion at 33.2 mg/dL, but compatible blood could not be found for him.
A rare case of haemolytic disease of newborn with Bombay phenotype mother - 
Shamee Shastry https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757779/

Anti-Jra

The direct coombs can be negative, but baby still be affected because infants can have low Jra antigen density immediately postpartum (basically the antigens aren't fully developed and in large quantities at birth).

Suspected anemia caused by maternal anti-Jra antibodies: a case report - 
Yasufumi Endo https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546206/

Anti-M

Like other antibodies in the MNS group, anti-M can cause issues even with a negative DAT.

" In the third case, hemolytic anemia required transfusion of the newborn, despite a negative direct Coombs' (DAT).....After delivery the infant's M antigen status should be determined, because a negative direct Coombs' test may be found even when M antigen is present in the infant and hemolysis is occurring."
Anti-M antibody in pregnancy. - Thompson DJ https://www.ncbi.nlm.nih.gov/pubmed/2771305

Severe hemolytic disease of the newborn caused by anti-M antibodies - Eduardo Alfredo Duro https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006517/

Maternal anti-M induced hemolytic disease of the newborn followed by prolonged anemia in newborn twins - Satyam Arora
http://www.ajts.org/article.asp?issn=0973-6247%3Byear%3D2015%3Bvolume%3D9%3Bissue%3D1%3Bspage%3D98%3Bepage%3D101%3Baulast%3DArora

Anti-Mta

Like other antibodies in the MNS group, anti-Mta can cause anemia even with a negative DAT. 

Anti-Mta associated with three cases of hemolytic disease of the newborn. -  Cheung CC http://europepmc.org/abstract/med/15373562