Should a reference laboratory discontinue testing for weak D for ALL patients?

The following question was sent on 10/19/00 to the e-network for discussion: Is it a good idea for a reference laboratory to discontinue testing for weak D for ALL patients? The laboratory in question performs Rh typing mainly for prenatal women and babies. According to the individual who referred this question, the Technical Manual states that weak D testing is only required for determining Rh labeling of donor units, and that the Standards do not require weak D typing for recipients of blood transfusions. The inquiring individual also states that the Technical Manual and the Standards are vague regarding the need to perform weak D testing for pregnant women. Based on the foregoing, if weak D testing of a pregnant woman is done and positive, should the pregnant woman be designated as Rh positive or negative? If she is designated as Rh positive, should she receive RHIG to protect her against future hemolytic disease of the newborn? The inquiring individual would like clarification of the intent of the Standards with regards to Rh typing of pregnant women and with regards to the use of RHIG for pregnant women who type weak D positive and who deliver an Rh positive baby. To make matters even more complex, the inquiring individual would like to know if RHIG should be given to an Rh negative woman who delivers a baby who types as weak D positive? The inquiring individual would also like to know if ACOG has established guidelines that address the above situations?

Here are the replies that were submitted in response to the above:

1. One of the small hospitals that comes under our jurisdiction was doing weak D testing on pregnant moms as well as all other Rh negative patients in order to reduce the amount of Rh negative blood transfused unnecessarily. On their AABB inspection they were cited for not providing a method to determine if the weak D in a pregnant mom was actually due to a feto-maternal bleed. A feto-maternal bleed can result in the mistyping of the mom as Rh positive when indeed she is Rh negative. The solution was to either cease the weak D testing for pregnant patients or have a method to detect the mixture as we do for moms after delivery - rosette test followed by Kleihauer-Betke, if indicated. Since the hospital in question is small with limited staff, they elected to just quit the weak D for this population.
   
   
2. The individual asking these questions on weak D testing should be addressing them to the AABB Standards committee for clarification. I'll be interested to see what discussion comes from the CBBS group, but the "intent" of the standards should come from the AABB.
   
   
3. According to Issitt and Anstee, "It is now appreciated that production of anti-D by persons with weak D on their red cells, who are transfused with D+, is a very rare event." pp. 328-330, Applied Blood Group Serology, Fourth Ed. As far as the reference laboratory testing for weak D: they are a consultation service and this should be included in the investigation. The question whether to test pregnant women for weak D has been an ongoing dilemma for years. If a pregnant woman types weak D positive, she is indeed D (RH) positive. Should she be issued RhIg? It probably won't hurt but is probably unnecessary; the probability of a mom being partial D is extremely rare.
   
   
4. Many laboratories around the world perform DNA-based genotyping for the RHD gene. We recently reported a study on RHD gene alterations that lead to incorrect genotype assignments for RHD in cases of feto-maternal incompatibilities (Allen et. al.. Genetic Testing, in press). Our recommendation from that study is that all information pertaining to parental genotype/phenotype be incorporated into the analysis of fetal genotyping results. Consequently, I would recommend that performing serological analysis for weak D phenotypes remain part of the laboratory workup for pregnant women at risk for RhD incompatibilities. Only with a complete picture of the genotype and phenotype of parents can an accurate prediction of fetal RhD phenotype be made.
   
   
5. The issue of weak D testing on mother and baby, and what to do about Rh Immune Globulin administration in various clinical scenarios is a difficult one. I do not think there is a consensus among transfusion medicine or Ob-Gyn professionals. For some guidance please see the recent publication: Domen RE. Policies and procedures related to weak D phenotype testing and Rh Immune Globulin administration. Arch Pathol Lab Med 2000;124:1118-1121 (August 2000). ACOG has established guidelines and recommendations that follow the AABB for the most part. However, from personal experience, I do not think all Ob-Gyn physicians necessarily agree with the established guidelines. There are documented cases of anti-D formation in individuals with the weak D phenotype following pregnancy or transfusion, and according to the above referenced paper, 31.8% of transfusion services reported seeing at least one anti-D alloantibody in weak D individuals over a 12 month period. Alternatively, if weak D testing is not performed then the patient will most likely be typed as Rh(D)-negative and could receive Rh Immune Globulin as a result. This is not necessarily a bad thing. It would be interesting to conduct a survey of Ob-Gyn physicians to see what they actually do in practice.
   
   
6. Reference laboratories, if they are performing ABO/Rh typing as a part of the test for compatibility, are not required to perform the test for weak D. That is clear. However, related to reference laboratory testing in general, I would look to the CLIA regulations for requirements, as they "regulate" the reference laboratory as a whole. I would look to 42CFR493.859, 42CFR 493.959, 42CFR 493.1271-1279. I would also see if California State Clin Lab has any requirements related to Clinical Laboratory testing other than the AABB Standards, which are the Standards for Blood Banks and Transfusion Services. You bring up a good point -- what direction is there for the clinical laboratory performing testing that is not pre-transfusion testing.
   
   
7. Well since it is our policy, I think it's a good idea not to test recipients for weak D. The problem with not doing it on OB patients comes when we perform the fetal screen test [looking for FMH] and we find out that the mom is a weak D. We then have it in our records that they are a weak D, and the next pregnancy they may or may not get RhIg. Also our old patients that are weak D's are not getting RhIg because we report them as D+. Thus, we currently have some inconsistencies in how to deal with OB's. The other situations where we routinely test for weak D are for bone marrow donors, newborns and autologous donors. Finally, Rh negative women who deliver a weak D baby should get RhIg. We send the mom's sample for Kleihauer-Betke because the fetal screen is not sensitive enough to detect a large bleed if baby is weak D. This is recommended in the mfrs. insert. A bulletin was sent out a couple of years ago with the ACOG and AABB recommendations. I believe they said weak D testing should be done on pregnant women but I am not sure what they said about whether the weak D women should be called D+ or D-. I know AABB has always felt they should be called D+ but ACOG has historically not trusted blood bank results and wanted these patients to receive RhIg if they are weak D. I don't have a copy of this bulletin so I am only guessing.
   
   
8. We do weak D testing on all prenatals. If weak D positive, we consider these individuals to be D positive and do not consider the women to be a RhIg candidate. If the mother is D negative and delivers a weak D positive infant then we consider her to be a candidate for RhIg since the baby is considered to posses the D antigen.

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