In the Partial D mechanism, various epitopes of the D protein are missing or altered. The red cells of some of these individuals may have weak or missing reactivity during routine testing with anti-D reagents. In contrast, others may show normal reactivity when typing with anti-D. This was first noted when individuals who had been typed as D positive formed anti-D.
Wiener and Unger postulated that the D antigen is made of antigenic subparts. Alloantibodies can be made against the absent subparts of the D antigen. Anti-D was produced in a D-positive patient warranting investigation, which led to the discovery of an antibody that behaved like an anti-D but was only reactive with normal D-positive and not partial D cells of the recipient.
Tippett and Sanger performed further studies resulting in the categorization of partial D, represented by Roman numerals I through VII. Category I has been deleted and several categories have been subdivided based on more sophisticated molecular testing methods.
Classifications of partial D are now made on the molecular level and are thought to be hybrid genes resulting from the replacement of sections of the RHD gene with sections of the RHCE gene. The protein changes occur external to the red cell membrane; therefore, when an individual with these altered proteins is exposed to normal D antigens during transfusion, they can make an antibody to the part of the RhD protein they lack. This antibody may cause hemolytic disease of the newborn or hemolytic transfusion reactions. Once identified, these individuals must receive Rh-negative blood products during transfusion. Most commonly, these individuals are recognized following the production of anti-D.
In a few cases, a D typing discrepancy may lead to further investigation. For example, a donor whose samples have tested D positive on multiple visits may surprisingly type as D negative. Further investigation may include a review of the records for changes in testing method and/or reagent antisera used. As in the case of weak D, the information in the reagent antisera's direction circular is crucial to understanding the potential for discrepancies in D typing.
