Desai A*, Tiwari N**, Chauhan AR***.
(* Second Year Resident, ** Assistant Professor, *** Professor, Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)
Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder that is secondary to accelerated destruction of platelet or impairment of thrombopoiesis by anti-platelet antibodies. We present a case of a 26-year-old primigravida with 33 weeks’ gestation with ITP, where thrombopoietin (TPO) analogue Eltrombopag (Revolade®) was used successfully. Patient had a falling platelet count despite injection methyl prednisolone and intravenous immunoglobulin (IVIG), and transfusions of Single Donor Platelets (SDP) and Random Donor Platelets (RDP), hence was started on eltrombopag. Though a category C drug, it was used when all other treatments failed and only in the third trimester; no adverse maternal or neonatal outcomes were noted.
Immune thrombocytopenic purpura (ITP) affects 1 in 10000 persons in the general population and the reported incidence in pregnancy is 1-2 per 1000 deliveries. ITP is responsible for 4% pregnancy associated thrombocytopenia.
Because of the side effects of drugs on the fetus and possible effects on course of pregnancy, the approach to treatment of ITP in pregnancy is different from that in non-pregnant state. Glucocorticoids are the initial drug of choice in the absence of major bleeding symptoms. Intravenous immunoglobulin (IVIG) and immunosuppressants are used in severe cases of ITP or those with bleeding. TPO mimetics like Eltrombopag and Romiplostim have been successfully used in non-pregnant patients but data regarding their effects on pregnancy are limited.
A 26-year-old primigravida 33 weeks of gestation was referred to us in view of low platelet count (45000 per cmm at the time of admission) and petechiae over the thigh. She was admitted in the intensive care unit in view of severe thrombocytopenia.
Diagnosis of ITP was made after complete hematological investigations, and bone marrow aspiration and biopsy, which was suggestive of hypercellular marrow consistent with peripheral destruction of platelets. The patient was jointly managed by the hematologist and obstetrician. Platelet counts were monitored on a daily basis and patient was given platelet transfusion twice in the pregnancy, 1 SDP and 2 RDP given at platelet count of 10000 cu mm. At platelet count of only 1000 cu mm, patient was given intravenous immunoglobulin, injection methyl prednisolone and azathioprine, after which counts improved. Patient was started on tablet eltrombopag 50 mg along with tab prednisolone 60 mg once daily when platelet count was 36000 per cu mm. Eltrombopag was continued throughout pregnancy and the dose was tapered to 25 mg once a day. Tab Prednisolone was also continued throughout pregnancy and then tapered and omitted in the postnatal period.
After starting treatment with eltrombopag, platelet counts initially fell below 30000 cu mm only once and she was given 1 SDP. After 1 week of treatment with eltrombopag, platelet counts rose and subsequently were always above 100,000 cu mm; she did not require further transfusions.
At 40 weeks 2 days of gestation, a decision for planned induction of labor was taken, after confirming availability of adequate platelets. However, the NST was non-reactive, hence patient underwent emergency LSCS. The outcome was a female child weighing 3420 gm with an Apgar score of 9/10. The peripartum and postpartum periods were uneventful and the platelet count at the time of discharge was above 100,000 cu mm. Patient was continued on tablet eltrombopag at the same dose (25 mg) in the postnatal period, for 6 weeks.
ITP is caused by antiplatelet antibodies also known as platelet associated immunoglobulin (PAIg) which bind to the glycoprotein complex on the platelet surface. These antibody- coated platelets are destroyed by tissue macrophages. The autoantibodies also affect megakaryocytic maturation thus reducing platelet production. Management decisions in cases of ITP depend on the platelet count and presence of bleeding symptoms. Glucocorticoids are the first line of treatment if the patient does not have major bleeding symptoms. Though safe for the fetus, they may induce gestational diabetes or hypertension in the mother. Cytotoxic drugs like azathioprine are teratogenic and thus not safe in early pregnancy. In our patient azathioprine was given only in third trimester. In case of life threatening bleeding the treatment of choice is IVIG, which is safe for the fetus but may cause adverse reactions in the mother; however, its effect is short lasting and not cost effective. Eradication of H. pylori with antibiotics has a positive impact on the platelet count in a patient with ITP.
Eltrombopag is a nonpeptide TPO receptor agonist. Mode of administration is oral. Eltrombopag is of benefit in patients who have not responded to steroids or IVIG. It increases platelet production by acting on the cMpl receptor. Eltrombopag belongs to pregnancy category C, to be used only when the benefits outweigh the risks, as in our case. Eltrombopag is usually started at a dose of 50 mg per day and modified as per the platelet count so as to keep the count above 50000 cu mm.[3,6] Daily dose should not exceed 75 mg as the most common complication is hepatotoxicity; the dose should be reduced in cases with liver disease. Side effects like rash, nausea, backache, diarrhea and upper respiratory tract infection may sometimes be seen. The main limitation at present to the use of eltrombopag, is the lack of studies in pregnant women and its prohibitively high cost.
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Desai A, Tiwari N, Chauhan AR. Use Of Eltrombopag In Immune Thrombocytopenic Purpura In Pregnancy. JPGO 2017. Volume 4 No.6. Available from: http://www.jpgo.org/2017/06/use-of-eltrombopag-in-immune.html