Successful maternal and fetal outcome in a rare case of essential Thrombocythemia with pregnancy using Interferon alpha

Through your esteemed journal, we are pleased and honored to write a case of uneventful pregnancy in a young woman suffering from essential thrombocythemia treated with interferon- a. Physicians caring for pregnant women with essential thrombocythemia face a difficult therapeutic decision. Careful observation might lead to thrombotic and obstetric complications, whereas cytoreductive therapy might have deleterious effects on the fetus. There is no consensus on the optimal treatment during pregnancy.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder with increased risk of vascular complications [1]. It is characterized by platelet count >600 000/µl, megakaryocytic hyperplasia, and splenomegaly with no alternative cause [2]. Two to three cases of ET are diagnosed per 100 000 individuals annually [3]. The median age of ET patients at presentation is around 60 years, though 20% of patients are women of child-bearing age [4]. It is more common in females, sex ratio M:F – 2:3 [5].

The risks of infertility, teratogenesis, and unfavorable pregnancy outcomes associated with the use of cytotoxic agents and/or with the disease itself cause concern with regards to the management of this subset of ET patients [6–8]. There is no consensus on the optimal treatment during pregnancy.

Our patient 27 years primi-gravida with history of essential thrombocythemia (ET) for last 2 years, was referred to us at 9 weeks. She was diagnosed as ET during medical check-up for a job. She was on Hydroxyurea for last 2 years. This was a planned conception; she stopped Hydroxyurea, received peri-conceptional folic acid and continued low dose aspirin. Platelet counts at the time of her first visit were 5.3 lacs. JAK2 (V617F) mutation was found to be negative. Fortnightly platelet count monitoring was done. Aspirin and folic acid were continued. At 17 weeks period of gestation, platelet count was 13 lacs, and she was started on interferon α, 3 miu, (s.c.) thrice weekly. She was diagnosed Gestational Diabetes Mellitus at 28 weeks, controlled on diet and insulin. At 29 weeks, she developed diagnosed Intra hepatic cholestasis of pregnancy and started on ursodeoxycholic acid. Her platelet counts gradually dropped to 3.5 lacs on Interferon alpha. At 34 weeks, Interferon alpha was stopped in view of her platelet counts being normal. While platelet counts monitoring was continued. Aspirin was stopped at 35 weeks. Fetal monitoring was done. She underwent elective caesarean section at 37 weeks for cephalopelvic disproportion. She delivered a 3.8 kg baby with no gross congenital anomaly. Injection Clexane 60 mg s.c. was started in view of her higher chances of thrombosis after 12 hours post op and continued for 2 weeks. Aspirin was started after 48 hours. Platelet counts started rising again and after 2 weeks. Platelet count was found to be 13 lacs and she was started on interferon- a. There were no signs of immunosuppression in baby.

ET in pregnancy has been reported to be complicated by spontaneous abortion (25–50%), intrauterine death (3–5%), stillbirth, premature delivery, preeclampsia (9%), and fetal growth restriction (4–5%) caused by placental infarction resulting from thrombosis. Live birth rate has been documented from 50–70% in various studies [8–11]. Maternal complications, such as bleeding or thrombotic events, may also occur during pregnancy or post partum [12], [13]. To improve pregnancy outcome and reduce maternal complications, the use of antiplatelet drugs and/or cytoreductive agents is often considered, but the optimal treatment is still controversial. Antiproliferative drugs such as Hydroxyurea could have adverse effects on the fetus (abortion, congenital malformations, or intrauterine growth restriction) [13–15]. Following early reports on safety and efficacy during pregnancy in women with ET, a-IFN is increasingly being used during pregnancy [16]. α-IFN is not mutagenic in vitro or teratogenic in animal studies; it does not reduce fertility [15–18]. Some reports have shown that IFN and IFN-like molecules are produced by murine and human placenta (trophoblast interferons). They are expressed for a short period in high concentrations, and have antiluteolytic, antiviral, Antiproliferative, and immunomodulator effects through receptors on the endometrial epithelium [19]. Pons et al. studied the pharmacokinetics of α-IFN in pregnant women in 1995 and demonstrated that α-IFN was undetectable both in the amniotic fluid and in fetal blood, and that the pharmacokinetic parameters did not differ from that in non- pregnant women [20]. Thus, at the doses used, α-IFN does not seem to cross the placenta and cannot cause any damage to embryogenesis or to the development of the immunologic system in the fetus [13]. Comparative analysis of 143 pregnancies in 75 cases in 27 studies showed improvement in live birth rate from 36% (with no treatment) to 71% after treatment with IFN alpha. Rate of spontaneous abortions declined from 35% to 14% after IFN alpha treatment [13]. Live birth rate up to 95% have been documented after treatment with INF-alpha in 122 pregnancies in 92 females in last 10 years in 17 canters of Italian thrombocythemia registry [21].

Optimal management of ET patients is still poorly defined, and there are no established protocols. However, we feel that during pregnancy all women are at risk of complication and should be treated. We suggest α -IFN to reduce platelet count, combined with ASA if no hemorrhagic complication is present

Acknowledgements

We acknowledge the co-operation and the permission given by Medical Superintendent to use the medical records for this case.

Declaration of interest: The authors report no declarations of interest.