Essential thrombocythemia (ET) is one of the chronic myeloproliferative diseases characterized by a markedly elevated platelet count in the peripheral blood due to an excessive proliferation of megakaryocytes in bone marrow, and thrombotic complications leading to marked morbidity. It is seen in almost every age group but peaks in the fifth decade. Therefore the association of this disease with pregnancy may be rare. Some cases are diagnosed during pulmonary embolism, venous thrombosis, or stroke etiology investigation and some on routine blood counting for any indication. Hydroxyurea, aspirin, interferon-α, and anagrelide are the preferred treatment choices (1–3). To our knowledge, this is the first case of multiple gestation in an ET patient who had elective cesarean delivery at 36 week of gestation treated with interferon-α during pregnancy. A 24-year-old woman applied to our Hematology Department complaining of fatigue and amaurosis one year before. Upon a routine blood count, platelets were elevated (1,050×109/l); we diagnosed ET after excluding other reasons for elevated platelets by bone marrow aspiration and cytogenetic studies. She was treated with interferon-α (Roferon, Roche, Basel, Switzerland), 4.5 million units (MU) subcutaneously, three times per week. She was a housewife and had a 2-year-old daughter. Interferon-α was well tolerated, with only fever episodes relieved by paracetamol and minimal flu-like symptoms in the first month of treatment. Interferon-α dosage was reduced to 3 MU three times per week in the second month of the treatment. Platelet count was about 350–450×109/l at the end of one year's treatment. She had no menses for two months at the 14th month of treatment. A pregnancy test was positive, and 6 weeks of twin gestation was reported on pelvic ultrasound examination. The family insisted on continuing the gestation and we planned an antenatal follow-up period at the perinatology clinic of our hospital. The pregnancy was dichorionic and diamniotic. Iron deficiency anemia occurring during the pregnancy was treated with oral iron supplementation. Until the 3rd trimester there was no change in platelet count and no sign of thrombosis or hemorrhagia. In the 3rd trimester the platelet count decreased to 140×109/l and we decreased the interferon-α dose to 1.5 MU three times per week. The pregnancy was terminated by elective cesarean delivery on the 36th week of gestation. Both of the infants were female, 48–49 cm height, 2,400–2,500 g weight, and healthy, and placenta was normal on examination. The infants’ complete blood counts were normal in the first week. ET patients are increasingly recognized in young adults because of the availability of automated complete blood counts. The ratio of fertile and pregnant patients is increasing within ET patients. Recent reports indicate that young patients have a slight risk of thrombosis, with potentially life-threatening complications (1). Patients with moderate thrombocytosis should be withheld without treatment until thrombotic and hemorrhagic complications occur. Emergency thrombocytapheresis may rapidly lower the platelet count with or without anti-aggregating agents such as aspirin. Low-dose hydroxyurea can also be used because of its high efficacy and its lower carcinogenic potential compared to alkylating agents. Interferon-α is a highly effective alternative therapy for patients with ET. Adequate control of platelet count can be achieved in most patients with ET. In our patient, interferon-α was instituted because she had a prominent increase in her platelet count and a history of amaurosis. Anagrelide, which interferes with megakaryocyte maturation, is another promising drug, currently under investigation. Asymptomatic patients with a moderate platelet count can be followed by frequent complete blood counting during pregnancy (1), (4). Whether vascular complications are increased by gestation in ET patients is debatable. There are some reported cases of miscarriage, particularly in the first trimester of pregnancy. In these cases aspirin can be useful. Congenital malformations are a major concern with chemotherapeutic agents, especially when used during the first trimester. In animals, hydroxyurea during pregnancy has resulted in severe developmental defects during the first trimester, whereas interferon-α has not been reported to be mutagenic or associated with congenital malformations in animals (4–6). Few cases in the literature treated with interferon-α had an abnormal fetus, suggesting that interferon-α does not alter fertility. It is unlikely that interferon-α could be teratogenic in humans, because this medication does not cross the placenta, as shown before (5), (6). Our case is the first multiple gestation with ET treated with interferon-α case in the literature. During pregnancy no maternal complications were observed because of primary disease or medication and healthy infants were born. It is likely that an asymptomatic pregnant women with ET could be followed up without medication. However, current data suggest that interferon-α may be used safely in pregnant patients who have ET and who required myelosuppression.
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Jul 15, 2020
John M Graham 
Open Access