RhD typing identifies human blood as being either positive or negative for the D antigen on the surface of red blood cells (RBCs).  During pregnancy, determining the correct RhD status of the expectant mother is particularly important in preventing alloimmunization and hemolytic disease of the fetus and newborn (HDFN).

What Is a Serologic Weak D Phenotype?

For several decades, blood donors and patients have been tested to determine their RhD status. However, over the years, it has been found that some patients have equivocal RhD results; that is, the results of one test will be RhD-positive, and another test RhD-negative. Though this was originally believed to be the result of errors in testing procedures, it is now known that this may be due to a serologic weak D phenotype.

Serologic weak D phenotypes occur because of variations in the expression of the D antigen on RBCs, caused by one of hundreds of known gene variants.  To err on the side of caution, clinicians commonly treat patients with serologic weak D phenotypes as RhD-negative; however, studies have shown that individuals with Weak D Types 1, 2 or 3 can be safely treated as RhD-positive. Only RHD genotyping can identify the specific gene variant responsible for a patient’s serologic weak D phenotype. 

Inconsistencies in Reporting RhD Status

In the United States, inconsistencies exist in the reporting of RhD results. Haspel and Westhoff (2015) discussed a College of American Pathologists (CAP) survey of 3100 U.S. laboratories that revealed variation in reporting the RhD status of patients with serologic weak D phenotypes. Of the 3100 facilities surveyed, 47 percent reported serologic weak D phenotypes as RhD-positive, 11 percent classified them as RhD-negative, and 30 percent used the term “weak D.”

Other factors contributing to these inconsistencies are whether the test is performed for a donor or a patient, and whether a patient is an adult or neonate. Each laboratory has its own policies regarding the classification of serologic weak D phenotypes. Because policies differ from one facility to the next, there can be confusion when a patient is seen at different centers.

The Importance of Accurate and Consistent RhD Classification

Studies have shown that some individuals with serologic weak D phenotypes are at risk for alloimmunization, while others are not; thus, some patients with serologic weak D phenotypes can be safely treated as RhD-positive, while others must be managed as RhD-negative. Only RHD genotyping can accurately determine the specific gene variant associated with a patient’s serologic weak D phenotype. Patients with Weak D Types 1, 2 or 3 are not at risk for alloimmunization and can be safely managed as RhD-positive, whereas patients with RHD gene variants other than Weak D Types 1, 2 or 3 should be treated as RhD-negative.       

In pregnant patients, it is especially important to correctly identify RHD gene variants associated with serologic weak D phenotypes, as RhIG prophylaxis must be given to some patients in order to prevent hemolytic disease of the fetus/newborn (HDFN) due to RhD alloimmunization.  On the other hand, wrongly classifying a pregnant patient with Weak D Type 1, 2, or 3 can lead to unnecessary use of RhIG, needlessly exposing a patient to a human-derived blood product and increasing costs to both patient and provider.

Benefits of RHD Genotyping

The use of RHD genotyping to determine a patient’s RhD status provides accurate information for appropriate patient management. RHD genotyping can reduce unnecessary RhIG prophylaxis, conserving RhIG supplies and reducing costs. Furthermore, RHD genotyping correctly identifies patients who are at risk for alloimmunization, and who should be treated as RhD-negative. 

RHD genotyping provides standardization in how patients with serologic weak D phenotypes are managed, eliminating the inconsistencies reported by Haspel and Westhoff (2015). Additionally, because RHD genotyping is a one-time test, and it can reduce unnecessary RhIG treatment in both current and future pregnancies, implementation of this testing may lead to cost savings over time.  

For more on RHD genotyping as it relates to obstetric patient management, download and read the Haspel and Westhoff (2015) study here