Many thanks to everyone who contributed to our case.
This week the case centred on a pregnant female who was an obligate carrier of Haemophillia A (Her Father was affected). She had a factor VIII level of 54%. She was a carrier of intron 22 inversion. The free fetal DNA testing in this case confirmed she is carrying a male fetus. In this situation CVS would be offered or Amniocentesis for pre natal diagnosis but the patient declined.
She was keen for an elective c-section as she lives some way from the specialist centre and after careful discussion this was arranged for 37 weeks. A comprehensive care plan was agreed with MDT:
- Premise is to assume baby may have Severe Haemophillia A
- C-section planned for 37 weeks safe to proceed if factor VIII >50% and also safe for spinal if threshold reached. To deliver between 9-5 and inform MDT on initiation of section.
- VTE prophylaxis safe if VIII level >60%
- Mechanical VTE prophylaxis and adequate hydration to be encouraged.
- If admission in spontaneous labour no fetal blood has sampling or fetal scalp electrodes. No forceps or ventousse.
- Urgent cord blood for factor VIII level.
- Oral vitamin K not IM.
- Any bleeding concerns contact Haem consultant on call.
- Neonatal team to review on delivery.
- Cranial USS will be required if affected baby.
- Actively managed third stage of labour.
She had a successful C-section and factor VIII level at delivery on the neonate is 36%. This is slightly lower than may be expected for a neonate but certainly excludes severe Haemophillia A a repeat sample at 6 months confirmed factor VIII level of 85%.
This case hopefully highlighted the importance of MDT working when caring for a pregnant patient.
Ideally this lady should have had pre-natal counselling and reproductive options discussed with her given her obligate carrier status. It is important when caring for patients with severe Haemophillia to contemplate extended family and offer genetic screening as appropriate particularly to females of childbearing potential.
Carriers of severe Haemophillia A should receive genetic counselling and the options of preimplantation genetic diagnosis discussed. In England the NHS will find 3 cycles of pre implantation genetic diagnosis with a success rate of around 30%.
Other options for diagnosis:
- Free fetal DNA to determine sex from 9 weeks gestation.
- Carriers of Haemophillia A and male fetus should be offered Pre natal diagnosis via CVS at 11-14 weeks gestation.
- Third trimester amniocentesis could also be considered for a male fetus.
If no diagnostic testing must treat male fetus as affected by Haemophillia A.
Antenatal care needs a coordinated MDT approach. In the case of Haemophillia A factor VIII levels generally rise during pregnancy from 6 weeks to around 2-3x baseline by term. Falling by day 2-3 post partum. Most carriers will have a level of 50-60% but lyonisation and ABO blood group can affect an individuals level.
Factor levels should be checked at booking and pre procedure as well as in third trimester to assist in planning for delivery. It should be noted that individuals carrying Haemophillia have an increased bleeding risk even when levels are between 40-60%. They are also at higher risk of PPH.
Factor VIII levels should be >50% for delivery and epidural. They should be >60% for LMWH prophylaxis.
If levels of VIII are low then DDAVP (0.3 micro grams per kg based on pre pregnancy weight) should be given as a trial. Tachyphalaxis can occur with repeat doses. DDAVP is contraindicated if any evidence of pre-eclampsia. A fluid restriction should be kept to 1 litre post treatment. If trial of DDAVP fails then recombinant factor VIII should be used with levels checked before and after doses and after 4-6 hours. Tranexamic acid should also be used. Treatment should be continued for 3-5 days post delivery depending on circumstances.
Intrapartum care should be agreed with MDT and an anaesthetic opinion as well as obstetric advice is vital. A plan should be written and agreed before 37 weeks.
The options of delivery need careful discussion but a vaginal delivery is not contraindicated though induction may be needed if concerns about distance from specialist care centre. The optimal mode of delivery is uncertain but there is an increased risk of ICH in babies born with assisted vaginal delivery especially ventose. There is a suggestion of lower risks of ICH with planned Caesarean section and this should be offered to mothers for discussion depending on other additional risk factors.
During labour fetal blood sampling, fetal scalp electrode use and mid cavity or ventouse should be avoided. IM vitamin K should not be given oral used instead until confirmation of babies Haemophillia status via urgent cord blood.
Post delivery tranexamic acid is recommended for mothers until bleeding post delivery stops or lightens to normal menstrual period. This is felt to be safe with breast feeding. Women should be advised lochia passage can occur for long period upto 58 days post delivery.
If the baby is affected then cranial USS is recommended due to increased rates of ICH in these babies. MRI may be considered if suspicion of ICH. Prophylaxis may be considered for premature babies or those with traumatic delivery on a case by case basis.
There is a highly comprehensive guideline available on which the above case advice has been taken:
Pavord S et al. RCOG Green top guideline no 71. Management of inherited bleeding disorders in pregnancy. BJOG 2017;124:e193-e263.