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Weak D Testing

Historically, weak D red blood cells were defined as having decreased D antigen levels that required the indirect antiglobulin test for detection. Weak D phenotype most commonly results from a single point mutation in the transmembrane domain of the RHD gene.  More than fifty different weak D types have been reported so far. Since the difference in D antigen expression is quantitative and not qualitative, the majority of patients with a weak D phenotype can be safely transfused with Rh positive red blood cells and do not form anti-D antibody. Rarely, individuals with specific weak D alleles such as type 4.2 and type 15 have been reported to produce anti-D antibodies.

Molecular studies have revealed another weak D phenotype that has been classified as partial D. Affected red cells contain a normal quantity of D antigen, which lacks at least one D-specific epitope due to amino acid changes within the extracellular portion of the D protein. Individuals with partial D phenotypes are capable of making antibodies against epitopes they do not express. In the United States, approximately 1% of patients has weak D and 1% has partial D variants.

Today, the anti-D blood group reagents that have been approved by the FDA contain both monoclonal IgM and IgG antibodies. The former detect D antigen during immediate spin and the latter detect D antigen in the antiglobulin phase of testing. Weak D phenotypes are detected with these reagents. Many weak D variants that previously were only detected in the antiglobulin phase using older polyclonal reagents are now detected by routine typing. 

Today, weak D antiglobulin testing is required for blood donors and newborns of D negative mothers to detect potentially immunogenic weak D red blood cells. Weak D typing is not required, nor encouraged, for transfusion recipients and pregnant women. By eliminating the antiglobulin phase of testing for these patients, some partial D variants at risk of forming anti-D will be classified as Rh negative. Therefore, these patients will be candidates for Rh immune globulin during pregnancy and transfused with Rh negative red blood cells. 

Controversy still exists regarding whether pregnant women who were previously identified as weak or partial D should be given Rh immune globulin prophylaxis. Arguments against giving RhIG include the relatively low risk of anti-D formation and the lack of evidence supporting its efficacy. Arguments in favor of RhIG administration include the possibility of a partial D phenotype and the unknown risk anti-D formation. In these situations, the medical director of the transfusion service should consult with the obstetrician.

Occasionally, discrepancies in D typing occur between laboratories because of the various methods and reagents used for testing. An obstetrical patient may have been previously tested for weak D in another laboratory or as a blood donor. Laboratories following current guidelines will not perform weak D testing and classify this patient as Rh negative. Another possibility is that an obstetrical patient, who really has a weak D phenotype but was classified as Rh negative, may have a falsely positive postpartum fetal rosette test due to reaction with maternal red blood cells. 


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