Anti-D Prophylaxis Reviewed in the Erea of Foetal RHD Genotyping

Abstract

A few years ago, the prevention of anti-D immunization was currently based on systematic postnatal prophylaxis associated with targeted antenatal injection in high-risk situations of foeto-maternal haemorrhage. The failures of prevention are mainly due to the non-respect of established guidelines for RhIG prophylaxis, and to spontaneous undetected foetal-maternal haemorrhages without any obvious cause during the third trimester of pregnancy.In order to reduce the rate of residual post-pregnancy anti-D immunization, several countries decided to associate the classical prophylaxis to a routine antenatal anti-D prophylaxis (RAADP) during the 28th or 29th week of gestation. Since about ten years, the foetal RHD genotyping in maternal plasma enables us to limit the antenatal prophylaxis only to those D-women carrying a D+ foetus. This paper deals with: the advantages of an antenatal prevention in the light of non invasive foetal RHD genotyping, the rules rendering prevention protocols efficient whatever the algorithm applied, and the recommended immuno-haematology follow-up of women who have received RhIG.

Anti-D Antibodies in Pregnant D Variant Antigen Carriers Initially Typed as RhD+

“…The low risk of RhD immunization in women with weak D types 1, 2 and 3 is the reason why most authors hold that women with prevalent weak D types do not require RhD immunoprophylaxis [5,10,11,12,13], and weak D patients could safely receive D+ RBC units [4]. Conversely, women with partial D should be classified as D- considering their prenatal management and RhD immunoprophylaxis [13,14].…”

“…Conversely, women with partial D should be classified as D- considering their prenatal management and RhD immunoprophylaxis [13,14]. In Europe, anti-D reagents are selected to deliberately type pregnant DVI carriers as D- to ensure that such mothers would receive RhD immunoprophylaxis in their second trimester and/or postpartum.…”

Usefulness of Non-Invasive Fetal RHD Genotyping towards Immunoprophylaxis Optimization

“…Their availability would make a great impact on regional public health policies both in the management of D-negative pregnant women and with regard to the optimization of the scarce resources available for prophylaxis. In other countries, it is well known that between 20 and 40% of D-negative pregnant women carry D-negative fetuses [11], and therefore in these cases prophylaxis is not necessary.…”

“…Therefore, non-invasive genotyping of fetal RHD status by analyzing cffDNA in maternal plasma has already been incorporated into routine clinical practice of many countries, causing a great impact on management protocols of D-negative pregnant women [10]. In Belgium, since 2002, fetal RHD genotyping has been used during the follow-up of D-negative pregnant women for an accurate indication of prophylaxis, and, in parallel, prevention policies have been implemented, allowing to avoid IgRH injection in 39% of the women who carry D-negative fetuses [11]. In Denmark, a national routine antenatal anti-D prophylaxis program implemented in 2010 guaranteed that administration of IgRH is based on the results of antenatal screening of fetal RHD gene and allows to avoid unnecessary use of prophylaxis in 37.3% of D-negative pregnant women [2,12].…”