A case of Fanconi anaemia in pregnancy

Abstract

Fanconi anaemia is a rare autosomal recessive chromosomal instability syndrome characterised by progressive bone marrow failure, skeletal defects, reduced fertility and increased susceptibility to malignancy. Successful pregnancy in both transplanted and non-transplanted patients have been recorded. In this paper, we present a woman diagnosed with Fanconi anaemia and who had a spontaneous conception at the age of 25 years with an uneventful delivery at 38 weeks of pregnancy.

Introduction

Fanconi anaemia is a rare autosomal recessive chromosomal instability syndrome characterised by progressive bone marrow failure, skeletal defects, reduced fertility and increased susceptibility to malignancy.^1–4 Endocrinopathies are a common feature of Fanconi anaemia. ⁵ Pregnancies are rare and the potential complications include low blood count, infection, haemorrhage, growth and placental dysfunction.^2,3

Case report

A 25-year-old woman was referred by her haematologist to the combined obstetric haematology clinic at 10 weeks’ gestation. She had been diagnosed with Fanconi anaemia when she was 15 years of age. She was heterozygous for the FANCA whole gene mutation, FANCA nonsense mutation PGlu 369 and she did not have a blood transfusion. She had a booking appointment for her pregnancy at 10 weeks and the booking bloods were normal apart from a low platelet count (Table 1), as was her blood pressure and urinalysis. Her body mass index (BMI) was 19.3 kg/m².

Table 1.

Blood results throughout pregnancy.

GA weeks	Hb g/l	Platelets ×109/l	WCC ×109/l	Neutrophils ×109/l	Reticulocyte count	Ferritin mcg/l	Vitamin B12
Booking	118	87	3.72	2.21	76	55
20	94	59	3.86	2.38	76		348
24	98	70	5.06	3.38
28	103	52	4.60	2.39	76
30	101	51	4.23	2.71	78	123
34	107	32	4.13	2.14	72
35	102	24	4.94	2.63	70
37 + 6	100	26	6.42	3.38
38	100	129	6.53

The patient was counselled about the effects of Fanconi’s anaemia on pregnancy and the impact which pregnancy may have on her condition. She was counselled about the risks of miscarriage, infections, placental abruption and low blood counts and the potential need for blood products.^1,3,4,6

She was commenced on low dose aspirin 75 mg once daily to reduce her risk of pre-eclampsia,^1,3,7 and she had regular fetal growth and umbilical artery Doppler scans from 26 weeks. She declined chromosomal screening. She was referred to the clinical geneticist who reassured her about the baby’s low risk of having Fanconi’s anaemia because the baby’s father was known to not be a carrier of the gene mutation.

Aspirin was stopped at 26 weeks when she had episodes of gum bleeding. She was treated with tranexamic acid mouth wash. Fetal growth scans, performed from 26 weeks of gestation, showed normal fetal growth and no placental concerns (Figure 1).

Figure 1.

Customised growth chart of the fetus.

She was reviewed in the obstetric anaesthesia clinic at 32 weeks, and she was advised against epidural and Entonox registered trademark sign please because of the risk of hematoma and bone marrow failure. ⁸ Spinal anaesthesia could be considered during labour if her platelet count were to be greater than 60x10⁹/L. She was also informed of a possibility of having platelet transfusion and antibiotics. The risk of postpartum haemorrhage was also discussed.

Her platelets dropped to 32 × 10⁹/L at 34 weeks, and a threshold for platelet transfusion was set at 20 × 10⁹/L.

The patient was admitted for induction of labour at 37 weeks. In view of the high risk of morbidity association with Fanconi’s anaemia, it was deemed safe and appropriate to induce labour once maturity was reached. Her blood results showed severe thrombocytopenia with platelet count of 26 × 10⁹/L at induction. Haemoglobin was 100 g/L. She was reviewed by the haematologist and she had two pools of platelets transfused when artificial rupture of membranes was performed, and two pools of platelets were reserved if needed. The platelet count after transfusion was 129 × 10⁹/L.

Continuous fetal monitoring was performed throughout labour and no concerns were identifed. She had diamorphine injection for analgesia during labour. She had a spontaneous vertex delivery of a live neonate. The baby was born in good condition with Apgar scores of 9 at 1 min and 10 at 5 min. Baby weighed 2680 g. The third stage of labour was actively managed with 1 ml oxytocin/ergometrine injetction, syntocinon infusion and 1 g tranexamic acid.

The estimated blood loss at delivery was 200 ml. Her blood pressure was normal after delivery. She was followed up by midwives, health visitor and GP in the community. Her platelet count remained stable at 124 g/x10⁹/L when she was seen at three weeks after delivery.

Clinical discussion

Fanconi anaemia is a rare autosomal recessive disorder with a prevalence of 1 in 136,000. It is commoner in people of Ashkenazi Jewish descent, Roma population of Spain and black South Africans. ⁹ Pregnancy is rare in women with Fanconi anaemia, and the literature is sparse on managing the condition in pregnancy and its potential complications. Some publications have quoted a pregnancy rate of 15% in those who have had no complications.^2,4

Fanconi anaemia is the most common inherited form of aplastic anaemia, and it is diagnosed in children between 3 and 14 years old.^1–3,9 It is diagnosed with full blood count, bone marrow biopsy and chromosomal fragility tests. Survival rates vary, and the outlook is poor in those with low blood count.^9,10 New and improved treatments such as bone marrow transplant have improved survival. Patients with Fanconi anaemia develop several types of blood disorders and cancers such as leukaemia.^1,3–5,10

Women who are pregnant are better managed in a multidisciplinary team that comprise of at least an obstetrician, haematologist, anaesthetist, specialist midwives with close collaboration from the blood bank services.^1,3,4,6,9 The major complications during pregnancy involve the effects of anaemia, neutropenia and thrombocytopenia on the pregnancy. Assessment of fetal growth and placental function may be advisable, especially if significant anaemia is present.

This condition and it's complications are not an routine indication for early induction of labour or caesarean section, the latter being reserved for obstetric indications only. The timing of delivery depends on the clinical status of the woman. The third stage needs to be actively managed, and any perineal trauma repaired expeditiously. We would suggest a low threshold to start an oxytocin infusion after delivery to reduce the risk of bleeding, as well as giving 1 g of intravenous tranexamic acid at delivery.

The close surveillance from a multidisciplinary team has resulted in a positive outcome in this case, and this remains the cornerstone in managing these patients.^1,3,4,6 Patients with Fanconi anaemia should be referred and managed in a tertiary centre to optimise their care.