Serologic testing for routine donor screening that can detect weak D types 38 and 11, particularly among populations in whom these variants are more prevalent, is strongly recommended, according to findings from a study conducted in southeastern Brazil and published recently in the journal Immunohematology.
Of the total 56 antigens carried by the Rhesus (Rh) blood group system, D is recognized as being the most immunogenic. In fact, anti-D is associated with hemolytic disease of the fetus and newborn (HDFN) and severe hemolytic transfusion reactions. In an effort to prevent formation of anti-D, standard practice involves the avoidance of transfusing D-positive red blood cells (RBCs) in D-negative individuals.
The large number of D variants can occasionally hamper the appropriate management of such patients, resulting in unnecessary utilization of Rh immune globulin, anti-D alloimmunization, and the overuse of D-negative RBC units.
The first D variant was discovered in 1946, with many variants reported since that time. It is recognized that in serologic tests, the majority of these variants demonstrate weak D reactivity (ie, ≤2+ in direct agglutination testing [DAT]). This may be indicative of either weak D variants, with no risk for formation of anti-D, or partial D variants that lack D epitopes, thus rendering anti-D alloimmunization a possibility.
Read more about HDFN signs and symptoms
Serologic tests are unable to differentiate between weak D variants and partial D variants. Further, certain partial D variants do not exhibit decreased reactivity in D typing or have a reaction that is stronger than 2+ on DAT—which is frequently recognized only following the formation of anti-D. In contrast, certain D variants exhibit very low antigen density, including DEL phenotypes and some weak D antigens, which are not detected in routine D typing.
Managing D variants differs among donors and patients. “A highly sensitive test is suitable for routine donor testing to cover D variants with low antigen density and avoid immunization of D[-negative] recipients.” In the patient typing routine, on the other hand, it is critical to identify partial D variants. Further, RHD genotyping is advised for samples that demonstrate a “serologic weak D phenotype,” in an effort to establish which patients are at risk for alloimmunization.
Recognizing that the prevalence of D variants differs among ethnic groups, the researchers sought to evaluate the serologic profiles of D variants and to establish which variants are associated the most with false-negative D typing results and alloimmunization.
They chose donor samples in 2 separate study periods:
- First period: D typing in donor routine testing was performed via use of a semi-automated instrument in microplates; weak D tests were carried out in tube or gel tests
- Second period: D typing was conducted via use of an automated instrument with microplates; weak D tests were carried out in the solid phase
Samples obtained from patients who were typed as D-positive with anti-D were chosen as well. All of the samples underwent molecular examinations during both study periods.
A total of 37 RHD variants were recognized. Results of the study revealed the following:
- Discrepancies and atypical reactivity without formation of anti-D were seen in 83.4% of samples
- Discrepant D typing findings between donations were observed in 12.3% of samples
- D-positive patients exhibiting anti-D were seen 4.3% of samples
DAR1.2 was the most common variant. Further, weak D type 38 accounted for 75% of the discrepant samples, followed by weak D type 11.
DIVa was the most common D variant linked to alloimmunization, and it was not recognized by serologic testing; this was true for DIIIc as well.
“The results highlight the importance of selecting tests for donor screening capable of detecting weak D types 38 and 11, especially in populations [in whom] these variants are more common,” the authors concluded.
