Successful pregnancy and delivery management in a patient with Bernard Soulier Syndrome

Introduction

Bernard Soulier Syndrome (BSS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of ristocetin-induced platelet aggregation. ¹ Jean Bernard and Jean-Pierre Soulier adescribed in 1948 what they called in French “dystrophie thrombocytaire hémorragipare congénitale”, later re-named BSS. ² The prevalence of this heterogenic syndrome is extremely rare and has been estimated at less than 1 in 1,000,000. The majority of cases are inherited in an autosomal recessive pattern. The main problem is in the glycoprotein Ib (GPIb)-V-IX function, which is responsible in primary hemostasis for initiating platelet adhesion at sites of vascular injury. ³ Most patients are identified with muco-cutaneous bleeding such as purpura, epistaxis and gingival bleeding in early childhood. Heavy menstrual bleeding is another bleeding pattern observed.^2,3

The multidisciplinary involvement of the Hematology and Perinatology departments is important in the management of thrombocytopenia and bleeding tendency, as bleeding during pregnancy can occur in almost 10% of pregnant women. ⁴ There are relatively few descriptions of BSS in pregnancy in the literature.

Case

A 24-year-old woman with BSS was followed up by our Hematology department as an outpatient and did not have platelet resistance. She was referred at the 6^th week of pregnancy. It was noted that she had been admitted with frequent nosebleeds and gastrointestinal bleeding in childhood. Flow cytometry was performed due to thrombocytopenia, and a significant decrease in CD42b expression was detected. In addition, a homozygous GP1BA mutation was identified in the mutation analysis. She had a history of platelet transfusion before tooth extraction 2 years previously.

She had not been pregnant before and followed at 2 weekly intervals in the first trimester together with her perinatologist. The initial platelet count was 6 × 10⁹/L and there were large platelets compatible with 60 × 10⁹/L in the peripheral smear. Since no bleeding was observed, follow-up was continued at 1-month intervals in the second trimester. At the 21^st week of pregnancy, epistaxis and gingival bleeding occurred, lasting for 36 h. One unit of platelet transfusion was given because bleeding continued despite local tamponade and ice application, and the bleeding stopped. No placental site bleeding or problems concerning the pregnancy occurred during the follow-up. As no recurrent bleeding occurred, follow-up was continued at 10-day intervals in the third trimester. After the 30^th week, platelet transfusion was given at 10-day intervals, because of the platelet half-life.

The patient was hospitalized at the 35^th week of gestation due to the presence of contractions. One unit of platelets was administered because of the low platelets of 9000×109/L on full blood count and 50,000×109/L on a peripheral smear. Platelet count was re-evaluated at 1 and 24 h after platelet transfusion. Both measurements showed similar results in peripheral smear and was evaluated as platelet refractoriness. Follow-up was done for 1 day, but due to the risk of preterm birth, antenatal dexamethasone was administered to accelerate lung maturation of the fetus. The method of delivery was decided as a caesarean section under general anesthesia, since the long duration of labor in the nulliparous gravida and uterine contractions would increase the risk of bleeding. A neonate weighing 2940 g was born with Apgar scores of 7 and 9 at 1 and 5 minutes respectively. The neonate had a normal platelet count. Recombinant activated Factor VII (rFVIIa), with off-label approval for use in delivery or bleeding, was administered at a dose of 10 mcg/kg for one hour before the caesarean section because of the platelet refractoriness. No excessive bleeding was observed while suturing the uterus but did occur during the closure of the muscle layer. Due to this excessive bleeding, 2 units platelet transfusion and 5 mcg/kg rFVIIa were administered. Powder absorbable hemostat (Surgicel®) patches were also applied locally over the muscle layer together with hemostatic sutures, and drains were placed to the pouch of Douglas and over the rectus muscles.

Elastic bandage was applied to both lower extremities as prophylaxis for thrombosis after delivery. Mobilization was encouraged on the evening of the delivery. Post-operative hemoglobin decreased (with ferritin: 19.4 ngml, transferrin saturation: 14.5%), a total of 3 units of red cells and 1000 mg intravenous iron carboximaltose were given. There was a total of less than 500 ml of bleeding from drains. Frequent leg exercises in bed were performed. One further unit of platelets was administered in the first two days in order to increase fibrin formation and accelerate wound healing. The drains were withdrawn on the second postoperative day. No abnormal bleeding or thrombotic events occurred. The patient was discharged home uneventfully on the 5^th day.

Discussion

Our literature review found very few successful pregnancies in patients with BSS. There is also a lack of a standard management approach. The first case described the successful delivery of a twin pregnancy complicated by preeclampsia and intrauterine growth retardation, reported in 1986. ⁵

The most extensive series was published in 2010 by Peitsidis et al. ⁶ In this review, there were a total of 30 pregnancies in 18 patients, of which 27 resulted in a live birth. While caesarean section was performed in 16 patients, vaginal delivery was undertaken in 11 women. Four patients had bleeding during pregnancy, 3 in the last trimester (36, 38, 40 weeks), but one woman had early bleeding at the 5^th week of gestation. When the methods used for treatment were examined, it is observed that platelet transfusion was the first choice (12 out of 18 patients). Tranexamic acid and desmopressin / 1-deamino 8 d-arginine vasopressin were also used. Bleeding between 200 and 1700 ml was observed in 9 women during delivery. In the first 24 h, postpartum hemorrhage was present in 33% of the patients, 40% had secondary postpartum hemorrhage. A total of 15 patients were given red cell transfusion. Alloimmune neonatal thrombocytopenia was reported in six neonates. ⁶ There are several more case reports after this review in the literature. In 2014, two cases were reported by Mitrovic M. et al., ⁷ one reported by Macedo et al. ⁸ in 2015, one by Smaoui et al. ⁹ in 2018, two by Fazal ABS, ¹⁰ and one by Perez et al. ¹¹

Caesarean section was the predominant route of delivery in these published cases. For vaginal delivery, it should be kept in mind that if the duration is prolonged after contractions start, the risk of bleeding may increase significantly. Regional anesthesia is contraindicated. Prophylactic platelet transfusion is recommended for all pregnant women before delivery is recommended for all pregnant women before delivery. During vaginal delivery, rVIIa may be used in combination with tranexamic acid. For caesarean section, human leukocyte antigen (HLA)-matched platelets and tranexamic acid are recommended as first-line treatment, but rFVIIa can also be added in the first line to reduce the risk of primary post-partum hemorrhage.^12,13 rFVIIa can be valuable especially in cases with platelet refractoriness. All neonates should have a full blood count. In addition to caesarean section, we gave our patient platelet transfusion at 10-day intervals due to the thrombocyte half-life, starting from the 30^th week. Although there is a risk of alloimmunization, we took this decision due to the frequency of bleeding history in our patient and the risk of uteroplacental separation, which may occur with the increased volume, venous dilatation and capillary leakage in the last trimester.

If the pregnant women referred with BSS have been diagnosed in another clinic, it is important to ensure the diagnosis is correct. The patient should be followed by the hematologist and the obstetrician. The patient and family should be warned about the potentially life-threatening bleeding during pregnancy and delivery. The mode of delivery should be discussed with the patient and multidisciplinary team.

The risk of post-partum thromboembolism should be taken into consideration, especially in cases who have had caesarean section and when rFVIIa is used. Other risk factors for thromboembolism (high body mass index, smoking, history of thrombosis, etc.) should be reviewed. After delivery, early mobilization should be ensured and this can also be supported through physical therapy, such as in-bed exercise. Elastic bandages or graduated compression, stockings should be preferred for mechanical prophylaxis, ¹⁴ all of which were performed in our patient. In the post-partum period, the patient should continue to be reviewed given the risks of secondary postpartum hemorrhage and thromboembolism.