British Society for Haematology (BSH) ‘Guideline for the investigation and management of red cell antibodies in pregnancy’ 

The British Society for Haematology (BSH) has recently published its updated ‘Guideline for the investigation and management of red cell antibodies in pregnancy’ [1]. The new name for the guideline mirrors the complementary UK Royal College of Obstetricians and Gynaecologists (RCOG) clinical guidance document, ‘The management of women with red cell antibodies during pregnancy’ [2]. The BSH guideline is intended to incorporate the necessary scope of the 2014 RCOG Green-top guidelines. 

While retaining the essential format and structure of the previous version (2016), it is worth noting that the numbering of sections has been updated, and two new sections have been added: ‘Requirements for Blood’ (Section 8) and "Obstetric Considerations" (Section 10).  

The main focus of the BSH guideline remains the antibodies anti-D, -c and -K which have significant risks for the fetus or neonate, including anaemia, jaundice, and perinatal loss. However, many other antibodies can cause anaemia or jaundice predominantly in the neonatal period (with occasional case reports of the fetus being severely affected) and/or pose challenges for laboratory screening and the timely provision of blood for the mother or baby. Red cell antibodies showing published clinical significance are outlined in table 3. 

In Section 5 ‘Antenatal testing protocols’, the recommendation for determining the blood group and antibody status of a pregnant woman is unchanged, with testing early in pregnancy (at booking) and at 28-weeks’ gestation to identify the ABO and RhD group and to detect potentially clinically significant antibodies. In the first algorithm (Figure 1) ‘Timing and frequency of antibody screening in pregnancy’, the recommendation is to now “offer” (rather than “consider”) paternal and fetal genotyping for clinically significant red cell antibodies, with further specific details provided within the guideline.  

In Section 6 ‘Red cell antibodies detected in pregnancy’, the second algorithm (Figure 2), ‘Management of anti-D, anti-K, or anti-c alloimmunisation’, reflects the guidance in this section and includes important changes that highlight the timing and thresholds for additional monitoring, testing, and referral to fetal medicine specialists. For women with immune anti-K, there is recognition of the ongoing uncertainty around the significant titres for anti-K levels (≥32 versus ≥4) and the importance therefore of early referral to a fetal medicine specialist on first detection of the antibody, irrespective of the antibody titre. 

The third algorithm (Figure 3) ‘Managing anti-D detection post-prophylaxis’, and subsection 6.1.1, help differentiate between passive and immune anti-D, noting our local criteria potentially vary based on Australian anti-D Ig dosing. 

With the increasing use of non-invasive fetal genotyping using cell-free fetal DNA (cffDNA) from maternal plasma, it is important to ensure testing is performed by the appropriate methodology and gestational age of the fetus to avoid false negative results. The timing and method are particularly noteworthy when comparing fetal genotyping for immunised mothers versus high-throughput screening of non-alloimmunised RhD negative mothers to target anti-D Ig prophylaxis (see subsections 4.6.1 and 4.6.2).  Information on Lifeblood fetal blood group testing, including a comparative table, can be found here. 

In summary, this guideline aims to improve the management of red cell antibodies in pregnancy, ensuring timely and appropriate interventions to mitigate risks to both the mother and fetus. 

Recommended further reading and listening on this topic – from the ‘How I Treat Transfusion Medicine’ series with international experts in the field, including from Australia 

You may also be interested in the recent publications in the journal Blood from experts in the management of pregnant women who are alloimmunised to red cell antigens and in the use non-invasive prenatal testing for red cell and platelet antigens [3, 4], as well as the accompanying editorial [5] and podcast interview with the authors [6].  

References 

1. Regan F, Veale K, Robinson F, et al. Guideline for the investigation and management of red cell antibodies in pregnancy: A British Society for Haematology guideline. Transfusion Medicine. 2025; 35(1): 3-23. doi:10.1111/tme.13098
2. Royal College of Obstetricians and Gynaecologists (RCOG). The management of women with red cell antibodies during pregnancy. Green-Top Guidelines. 2014;65:1-26.
3. van ’t Oever RM, Verweij EJT, de Haas M; How I use noninvasive prenatal testing for red blood cell and platelet antigens. Blood 2025; 145 (20): 2266–2274. doi: https://doi.org/10.1182/blood.2023022893 
4. Savoia HF, Parakh A, Kane SC; How I manage pregnant patients who are alloimmunized to RBC antigens. Blood 2025; 145 (20): 2275–2282. doi: https://doi.org/10.1182/blood.2023022894 
5. Erica M. Wood; Introduction to a How I Treat series on transfusion medicine. Blood 2025; 145 (20): 2233–2234. doi: https://doi.org/10.1182/blood.2025028947
6. Blood Podcast – How I treat series: How I Treat Transfusion Medicine (part 1)