Successful Pregnancies in Acquired Hemophilia Patient

Intoduction. The appearance of the inhibitor to FVIII in women of fertile age occurs in 10% of the total number of acquired hemophilia of different genesis, associates with a risk of miscarriage and the development of life-threatening postpartum bleeding. 15 women with postpartum acquired hemophilia are observed in the National Research Center for Hematology in Moscow.

Case report. We present a case-report of pregnancy management of a 30-old woman with acquired hemophilia. First clinical symptoms appeared the one year after the first normal delivery and were presented as spontaneous hemarthrosis and hematomas of soft tissues of various localizations. The patient was repeatedly examined in different hospitals. However, the diagnosis was not established. For the first time, disorders of plasma hemostasis were detected in 2012: the significant increase in APTT up to 140 seconds, the decrease in FVIII activity (0.5%) and the appearance of the inhibitor to FVIII (317 BE). Thus, the diagnosis of acquired hemophilia was verified. After a comprehensive examination, the metaplastic genesis of the disease, autoimmune diseases, and lymphoproliferative disorders were excluded. Dynamic monitoring of hemostasis revealed fluctuations in the inhibitor titer from 304 to 1300 BE.

Since 2012, the patient received therapy with eptactagog alpha (activated) on demand in standard doses of (90-120 μg/kg). The effectiveness of treatment was valued as high. In 2014 she had a second pregnancy that was tailored on prophylaxis therapy with rFVIIa at a dose of 7.2 mg/day (110 mg/kg body weight). Bleeding episodes during pregnancy were not observed. The delivery was performed under the hemostatic support of rFVIIa in a daily dose of 57.6 mg without any hemorrhagic complications. After the delivery maximum inhibitor titer was 1560 BE. The transient inhibitor was detected in the newborn (6 BE), it was eliminated by the three infusions of IVIG.

After delivery clinical picture was presented with recurrent hematomas of soft tissues. The average frequency of bleedings was 4-6 times a month. Three injections of eptacog alpha (activated) at a dose of 7.2 mg were required to stop the bleeding episode.

In January 2016 due to the severe clinical phenotype of the disease, a course of Rituximab therapy was conducted to eliminate the presence of a consistently high titer of the inhibitor. Two infusions (500 mg) were performed without additional high-dose therapy with FVIII concentrates and the use of by-pass products. Three months after the second infusion of anti-CD20, the inhibitor titer to FVIII was 0 BE, APTT 35 seconds, FVIII 64% (April 2016).

A month after the second infusion of Rituximab, the patient was pregnant with her third child. She received IVIG treatment at 4-5 weeks of gestation. At the gestational age of 7-8 weeks pregnancy complication was diagnosed - chorion abruption with a detachment area of 11,0 x 4,0 mm. It was treated with Duphaston. At the gestational period of 14-15 weeks another pregnancy complication was observed - uterine bleeding with the formation of bruising on the front wall of the uterus. It required a hemostatic therapy with rFVIIa at doses of 70 μg/kg of body weight with an interval of 12 hours. Coagulation parameters were in normal values: APTT 41 sec., PTI 94%, ATIII 102%, fibrinogen 4.2 g/l, D-dimer 159 ng/ml. Later on during the pregnancy there were no other complications, therapy with rFVII was not required. Physiological delivery was fulfilled at 38 weeks of gestation without any hemostatic support and bleeding complications. The baby was healthy.

Conclusion. Hemostatic effect of prophylaxis with rFVIIa allowed us to manage pregnancies and physiological deliveries of patient with acquired inhibitor to FVIII without any significant bleeding complication.