Pregnancy in a woman with Bombay blood group

Introduction

Bombay phenotype is a rare blood group where an individual does not express A, B, or H antigens, which are characteristic of the common blood groups. Pregnancy in women with this phenotype is complicated by the limited availability of compatible units of red blood cells, because these women have anti-A, anti-B and anti-H antibodies. The presence of the anti-H antibody means that even red cells of the ‘O’ blood type, which express the H antigen, are incompatible . Therefore, only red cells from a donor with the rare Bombay phenotype are compatible for transfusion. Described here is a case of a pregnant woman found to have the Bombay phenotype, and a review of the key aspects of her antenatal and intrapartum management.

Case

A 29-year-old woman from Goa, India, was pregnant for the first time. Antenatal blood tests showed the presence of anti-H antibody. Total anti-H titre (IgM and IgG) was 1:128 at 13 weeks’ gestation. The IgG anti-H titre was 1:256 units at 18 weeks and 1:128 by 25 weeks.

She had no past medical history, or history of prior blood transfusions. Her medications were ferrous sulphate and vitamin D daily. Her haemoglobin was 144 g/L, ferritin was 134 ng/mL, and B12 and folate were normal.

Due to the risk of haemolytic disease of the fetus and newborn (HDFN), fetal monitoring was undertaken with serial growth and middle cerebral artery (MCA) Dopplers. A detailed growth scan at 33 weeks of gestation showed estimated fetal weight on the 15^th centile and normal MCA Doppler.

Induction of labour at 38–39 weeks’ gestation was planned. After discussion with the national blood transfusion laboratory, it was established that two compatible units would take 12 h to be available due to the need to thaw and transport the frozen red cells. A plan was made to arrange the donation of fresh units from another individual with Bombay blood group, to be made within 5 days of the planned delivery date.

Active management of the third stage of labour was advised, and cell-salvage techniques were planned in case of a requiring a caesarean delivery.

In case of lack of availability of compatible products, transfusion of Rh/K compatible group O units with concurrent intravenous methylprednisolone and intravenous immunoglobulin (IVIG) was planned.

At 35 weeks’ gestation, the woman presented with spontaneous rupture of membranes. The local and national blood transfusion laboratories were immediately alerted. Three available units of O-ve, Rh/K compatible units were cross-matched due to the lack of immediate availability of compatible units . After 90 min, cardiotocography showed a pathological trace. She was found to be fully dilated, and a female infant in good condition was delivered with forceps. She was given Syntometrine^® (oxytocin and ergometrine) and tranexamic acid. Estimated blood loss was 350mls. After delivery, the mother was monitored closely, and there was no post-partum haemorrhage (PPH).

The infant weighed 2115 g. Cord blood was sent for full blood count (FBC), direct antiglobulin test (DAT), bilirubin, reticulocytes, and film microscopy. The cord FBC sample clotted but haemoglobin on the cord blood gas was 161 g/L, bilirubin 52 umol/l, and DAT was positive (IgG +1.). Due to the elevated bilirubin, the neonate received phototherapy for the first 12 hours of life, with an appropriate decrease in bilirubin. Haemoglobin at 9 h life was 159 g/L and remained stable, with no abnormalities detected on blood film. The baby was admitted to the neonatal unit at 27 h of life due to episodes of hypoglycaemia which required enteral feeding, and was discharged from the unit on the third day of life. The neonate's blood group was B, rhesus positive.

In the postnatal period, the woman was contacted, and both the possibility of her joining the rare blood donor list as well as autologous blood donation in advance of a future pregnancy was discussed.

Discussion

The H antigen is the substrate for the two antigens that make up the ABO blood group and is converted to the A or B antigens by glucosyltransferase enzymes. It is produced by fucosyltransferase enzymes encoded by the FUT1 and FUT2 genes. H antigen is expressed on RBCs and secretory gland cells. ¹

‘Bombay phenotype’ individuals are homozygous for a mutation of the FUT1 and FUT2 genes. Unable to express the H antigen, the individual develops anti-H antibodies in the serum. ¹ At 37 degrees, the antibody agglutinates with H antigen and causes intravascular haemolysis of transfused group O red cells.^2,3

The Bombay phenotype is very rare. It was first discovered in Mumbai in India, where the prevalence is 1 in 7600,^1,4 and in Europe, it is reported in the literature to be 1 per 1,000,000 ⁵ although with increasing global migration, the modern incidence may be higher. There are 12 published reports where the antenatal management in pregnancy is described.^3,6–16

Maternal concerns

The main maternal concern is that of the potential requirement for red blood cell transfusion for the management of haemorrhage. Women should be transfused with H antigen-negative blood to prevent a haemolytic transfusion reaction. Regular discussion with the national blood transfusion laboratory throughout the pregnancy is important in planning antenatal care and delivery. Due to rarity of compatible donors, only very limited numbers of frozen compatible units were stored in the national blood transfusion laboratory. Due to their scarcity, no units were defrosted and transported electively prior to delivery, considering the patient's low overall risk of peripartum haemorrhage, the risk of wastage, and the need to preserve these units for situations of high clinical need. Frozen units would have taken several hours to be thawed and transported and so would have been of limited utility in an emergency such as major haemorrhage. In women considered to be at higher risk of PPH, immediate liaison with the national transfusion laboratory at the start of labour could allow the relevant units to be made available.

In an attempt to provide available fresh compatible units, a donation from a registered Bombay phenotype blood donor was planned to take place within 5 days of the delivery. Induction of labour was therefore planned at 38–39 weeks of gestation, in order to coordinate with this planned donation, to reduce the chance of delivery out of hours, and also because of the reduced sensitivity of MCA Doppler measurement after 37 weeks’ gestation. However, ultimately, this donation did not occur due to the onset of spontaneous pre-term labour. To mitigate against this risk of pre-term labour, earlier fresh compatible unit donation in pregnancies could be considered, especially in women predicted to be at increased risk of pre-term labour and peripartum haemorrhage, although timing this with the onset of labour would present significant challenges.

It was important to minimise the likelihood of PPH in the management of such pregnancies. Both optimisation of haemoglobin and iron stores during pregnancy and active management of the third stage are advised. ¹⁷ The use of prophylactic tranexamic acid should be considered, especially in those women undergoing caesarean section and those at increased risk of PPH. ¹⁸

Intra-operative blood salvage is recommended in the case of delivery by caesarean section, and has been employed in a case of post-partum haemorrhage in a woman with Bombay phenotype.^10,19,20 Cell salvage has also been demonstrated as feasible in vaginal deliveries outside of the operating theatre. ²¹ While more trial data is required to demonstrate its safety and effectiveness before it can be recommended routinely, it could be considered depending on local expertise and equipment. The use of prepartum autologous transfusion has been described elsewhere,^11,12 but risks depleting the maternal haemoglobin and increasing the need for transfusion at delivery. However, pre-conception donation and storage of frozen red cells should be considered.

Despite the above measures designed to maximise the chances of availability of compatible units, and minimise the chance of their requirement, in the event of a life-threatening obstetric haemorrhage, it may be necessary to transfuse non-Bombay group O cross-matched blood while awaiting compatible units. In this situation, concurrent administration of methylprednisolone and IVIGs may reduce the likelihood or severity of transfusion reactions.^22,23 Their use has been reported in the management of a transfusion reaction due to anti-H, and they are compatible with pregnancy.^24–26

Fetal and neonatal concerns

HDFN is a risk in a Bombay phenotype pregnancy, due to transfer of the IgG form of the anti-H antibody across the placenta. This results in the destruction of fetal red cells. ²⁷ Conversely, the IgM form of the antibody does not cross the placenta and has no fetal implications. Although maternal anti-H is usually predominantly of the IgM form, HDFN has been reported in pregnancies with maternal Bombay phenotype, with the risk of the fetus or neonate requiring intervention occurring generally at IgG titres >1:64. In this case, the IgG specific titre was 1:256 at 18 weeks of gestation, rising to 1:256 at 25 weeks, and therefore the patient was at risk of HDFN. For this reason, fetal monitoring was undertaken with serial ultrasound and MCA Dopplers. Antenatal fetal genotyping was not available for anti-H. At birth, although the baby required phototherapy for jaundice and the DAT was positive, given the stable haemoglobin and normal blood film, this was likely related to prematurity rather than HDFN.

Conclusions

In conclusion, careful multidisciplinary antenatal planning is crucial in pregnant women with Bombay phenotype in order to reduce the risk of bleeding and transfusion requirement at delivery, to facilitate the availability of compatible blood products at delivery, and to plan for circumstances where no available compatible units are available for transfusion.