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CASE REPORT Table of Contents   
Year : 2016  |  Volume : 10  |  Issue : 2  |  Page : 155-158
A case of refractory immune thrombocytopenia in pregnancy managed with elthrombopag


1 Department of Transfusion Medicine, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India
2 Department of Obstetrics and Gynecology (OBG), Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India

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Date of Web Publication8-Aug-2016
 

   Abstract 

Immune thrombocytopenic purpura is a common acquired autoimmune disorder defined by a low platelet count secondary to accelerated platelet destruction or impaired thrombopoesis by anti-platelet antibodies. Thrombopoietin (TPO)-mimetic drugs such as eltrombopag and romiplostim have been used successfully in many nonpregnant individuals with immune thrombocytopenia (ITP) but studies based on its effects in pregnancy are limited. A 27-year-old multigravida who is a known case of ITP with bad obstetric history was referred to the Department of Obstetrics and Gynecology at 26 weeks of gestation with complaints of mucosal bleeding and recurrent abortions. After 2 weeks of hospital stay, the patient did not respond to treatment with steroid and immunosuppressant. There was a rapid decline in platelet count with mucosal bleeds for which she required frequent platelet transfusions. Due to high costs, short action periods, and other potential maternal and fetal side effects of intravenous immunoglobulin (IVIgG) and anti-D, it was decided that TPO-mimetic drug eltrombopag would be given. After starting treatment with eltrombopag, the patient's platelet count could be maintained between 30,000/μl and 50,000/μl. At 36 weeks of gestation following preterm-induced vaginal delivery, she delivered a male active baby weighing 1.86 kg with an Apgar score of 8/10. After delivery, her platelet count was 60,000/μl. Eltrombopag is a thrombopoietin receptor agonist. It has been assigned to pregnancy category C by the Food and Drug Administration (FDA). There are no adequate and well-controlled studies of use of eltrombopag in pregnancy. In our case, the drug was given in the last trimester of pregnancy and the mother and baby were in good health at the time of discharge from the hospital and during follow-up.

Keywords: Eltrombopag, immune thrombocytopenic purpura, neonatal alloimmune thrombocytopenia (NAIT), platelet transfusion

How to cite this article:
Purushothaman J, Puthumana KJ, Kumar A, Innah SJ, Gilvaz S. A case of refractory immune thrombocytopenia in pregnancy managed with elthrombopag. Asian J Transfus Sci 2016;10:155-8

How to cite this URL:
Purushothaman J, Puthumana KJ, Kumar A, Innah SJ, Gilvaz S. A case of refractory immune thrombocytopenia in pregnancy managed with elthrombopag. Asian J Transfus Sci [serial online] 2016 [cited 2021 Sep 18];10:155-8. Available from: https://www.ajts.org/text.asp?2016/10/2/155/177204



   Introduction Top


Immune thrombocytopenic purpura is an acquired autoimmune disorder characterized by a low platelet count secondary to accelerated platelet destruction and impaired thrombopoiesis as a result of circulating antiplatelet antibodies directed against platelet glycoproteins.[1] Immune thrombocytopenia (ITP) has been estimated to affect approximately 1 in 10,000 in the general population; about half of them are children. The incidence of ITP during pregnancy is reported to be 1-2 per 1,000 deliveries.[2] ITP is responsible for 4-5% pregnancy-associated thrombocytopenias.[3] The most important fetal or neonatal complication of ITP in pregnancy is “fetal or neonatal alloimmune thrombocytopenia.”[4]

The approach to treatment of ITP during pregnancy is different from that in nonpregnant women because the potential side effects of drugs may complicate fetal development and the course of pregnancy. Glucocorticoids are considered for initial therapy if there are no life-threatening bleeding symptoms. Other treatment options include intravenous immunoglobulin (IVIgG), which is safe for the fetus but often associated with maternal side effects and high costs. Experience with anti-Rh(D) therapy in pregnant women is limited.[4] TPO-mimetic drugs such as eltrombopag and romiplostime have been used successfully in many nonpregnant individuals with ITP but studies and experiments regarding its effects on pregnancy is limited.[5] We present here a case of refractory ITP in pregnancy managed with elthrombopag.


   Case Report Top


A 27-year-old multigravida, a known case of ITP, was referred to the Department of Obstetrics and Gynecology at 26 weeks of gestation with complaints of spotting per vagina and petechial spots over her face and limbs. She was a fifth gravida with a bad obstetric history of three abortions and one neonatal death.

Diagnosis of ITP was made after her second pregnancy and treatment was started with steroids and immunosuppressant. Splenectomy was advised but she refused due to fear of surgery.

She was given platelet transfusions three times in the current pregnancy before she was admitted to our hospital. She was on azathioprine 50 mg and prednisolone 40 mg daily since 2 months. Her platelet count was 10,000/µl at the time of admission. She was transfused with four units of platelets.

Laboratory investigations for antinuclear antibody, beta 2 microglobulin, lupus anticoagulant, anticardiolipin antibodies were negative and all other causes of recurrent abortion were ruled out. All other blood investigations were normal except for a prolonged bleeding time. The details are listed in [Table 1].
Table 1: Blood investigations

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She was given a full course of anti-Helicobacter pylori (H. pylori) medication. After 2 weeks of hospital stay, there was no satisfactory rise in her platelet count and her symptoms worsened. She did not respond to steroid and immunosuppressant. She required frequent platelet transfusions. Other treatment options of ITP had to be considered such as intravenous (IV) immunoglobulin, anti-D, and TPO-mimetic drugs. Due to high costs, short action periods, and other potential maternal side-effects of IVIgG and anti-D, it was decided that TPO-mimetic drug eltrombopag would be given at 29 weeks of gestation. Elthrombopag 25 mg once daily (OD) was given for 7 days. The dose was then increased to 50 mg. After 2 weeks of treatment with eltrombopag, her platelet count became 30,000/µl. Eltrombopag was continued till delivery [Table 2].
Table 2: Platelet count, management, and clinical conditions of the patient from the time of admission to discharge from the hospital

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After starting treatment with eltrombopag, her platelet count never went below 30,000/µl and she had no signs and symptoms of bleeding. Platelet transfusion was not given to the patient till delivery after the commencement of treatment with eltrombopag.

At 36 weeks of gestation, she delivered an active male baby weighing 1.86 kg with an Apgar score of 8/10. During delivery, she was given 6 units of platelet transfusion due to anticipated bleeding. The postpartum and peripartum periods were uneventful.

After delivery, her platelet count was 55,000/µl. Eltrombopag was discontinued. Platelet count of the baby was 145,000/µl on the first postnatal day. The baby's platelet count dropped to 55,000/µl by the third postnatal day. Suspecting neonatal alloimmune thrombocytopenia (NAIT), IVIgG was started due to the risk of intracranial hemorrhage. After two doses of IVIgG, the baby's platelet count increased to 155,000/µl. The mother and baby were discharged from the hospital 2 weeks after delivery. At the time of discharge from the hospital, her platelet count was 60,000/µl and that of the baby was 249,000/µl. She was reviewed 6 weeks after delivery. Both the mother and baby were in good health. Her platelet count was 70,000/µl.


   Discussion Top


ITP is caused by antiplatelet antibodies called platelet-associated immunoglobulin (PAIg), which binds to glycoprotein (GP) llb/llla complex or GP1b/IX complex or other glycoprotein complexes. This antibody-coated platelets are destroyed by tissue macrophages located primarily in the spleen.[6],[7] A marked reduction in platelet production was also observed in acute and chronic ITP since autoantibodies against this platelet glycoprotein interfere with megakaryocytic maturation.[8],[9]

The most common condition confused with ITP is gestational thrombocytopenia, which occurs in 4-8% of the pregnancies. Gestational thrombocytopenia is likely when an otherwise healthy woman with a previously documented normal platelet count develops mild thrombocytopenia with platelet count between 70,000/μl and 100,000/μl in the third trimester of an uncomplicated pregnancy. ITP generally causes moderate to severe thrombocytopenia in the first trimester. ITP may exacerbate during pregnancy but generally the platelet count returns to the prepregnancy level after delivery.[10]

While treating ITP during pregnancy, the potential side effects of the drugs have to be considered as they affect the course of the pregnancy and the development of the fetus. A multidisciplinary approach should be adopted to manage the mother and fetus with the help of a hematologist, an obstetrician, and a neonatologist.

Glucocorticoids are considered for initial therapy if there is no life-threatening bleeding. Glucocorticoids are not teratogenic but they can induce gestational diabetes or hypertension. Cytotoxic drugs, such as vinca alkaloids, azathioprine, and cyclophosphamide, are potentially teratogenic. In our patient, azathioprine was started during the second trimester. The rigors of splenectomy may induce preterm labor and so it was not considered for our patient. IVIg should be considered if patients fail to respond to glucocorticoids and if there is life-threatening bleeding, IVIg is safe for the fetus but is often associated with maternal side effects, its effect is transient, and it is not cost-effective. Experience with anti-(Rh)D therapy in pregnant women is limited.[4]

Some studies showed that eradication of H. pylori with antibiotics resulted in a marked increase in the platelet count in patients with ITP.[11]

Platelet count and bleeding symptoms are important for the management of these patients. A platelet count above 30 × 109/L with no bleeding symptom requires only observation. Platelet transfusions are required if a pregnant woman has a platelet count of less than 10 × 109/L in any trimester, a platelet count of 10 to 30 × 109/L in the third trimester, or if there is any sign of bleeding.

Vaginal delivery can be performed with a platelet count above 50 × 109/L. Platelet count should be raised to 80 × 109/L if caesarean section is considered.[4] Platelet count of less than 30 × 109/L requires platelet transfusions to prevent maternal bleeding during labor.[4],[12]

Eltrombopag olamine is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia that has had an insufficient response to corticosteroids, immunoglobulin, or splenectomy. Eltrombopag is a nonpeptide thrombopoietin receptor agonist for oral administration. Eltrombopag interacts with the transmembrane domain of the thrombopoietin receptor (cMpl) leading to increased platelet production. It triggers megakaryocytic growth and differentiation.[5]

Eltrombopag is initiated with 50 mg OD dose for most patients with chronic ITP. The initial dose can be reduced in patients with hepatic impairment. The dose can be adjusted to maintain a platelet count of ≥50 × 109/L.[5],[13] Daily doses should not exceed 75 mg. A 25 mg OD dose was tried for our patient due to cost constraints and considering pregnancy but the dose was changed to 50 mg OD as we failed to achieve a rise in platelet count as expected.

Eltrombopag has been assigned to pregnancy category C by the Food and Drug Administration (FDA). There are no adequate and well-controlled studies of eltrombopag use in pregnancy. Eltrombopag should be used in pregnancy only when benefit outweighs risk. In animal reproduction and developmental toxicity studies, there was evidence of embryo lethality and reduced fetal weights at maternally toxic doses. In our case, the drug was started during the third trimester and so there was no question of embryo lethality.

The most common adverse reactions include nausea, diarrhea, upper respiratory tract infection, vomiting, myalgia, urinary tract infection, oropharyngeal pain, pharyngitis, back pain, influenza, paresthesia, and rash. However, our patient had no such adverse reactions.

The most important complication of this drug is hepatotoxicity and so the monitoring of liver function before and during therapy is very essential. For our patient, liver function tests were performed before starting therapy with eltrombopag and it was repeated every 2 weeks and before discharge from hospital [Table 3].
Table 3: Liver function test before and after starting treatment with eltrombopag

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   Conclusion Top


Eltrombopag can be considered as a treatment option in transfusion-dependent pregnant patients with ITP who failed to respond to steroids and immunosuppressant. We can also reduce the risks associated with repeated platelet transfusions.

Acknowledgement

We would like to acknowledge the doctors and other staff of the Department of OBG of Jubilee Mission Medical College, Thrissur, Kerala, India.

Financial support and sponsorship

In the form of grants, equipment, drugs, or all of these.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
George JN, Woolf SH, Raskob GE. Idiopathic thrombocytopenic purpura: A guideline for diagnosis and management of children and adults. American Society of Hematology. Ann Med 1998;30:38-44.  Back to cited text no. 1
    
2.
Kelton JG. Idiopathic thrombocytopenic purpura complicating pregnancy. Blood Rev 2002;16:43-6.  Back to cited text no. 2
    
3.
McCrae KR, Samuels P, Schreiber AD. Pregnancy-associated thrombocytopenia: Pathogenesis and management. Blood 1992;80:2697-714.  Back to cited text no. 3
    
4.
Letsky EA, Greaves M. Guidelines on the investigation and management of thrombocytopenia in pregnancy and neonatal alloimmune thrombocytopenia. Maternal and Neonatal Haemostasis Working Party of the Haemostasis and Thrombosis Task Force of the British Society for Haematology. Br J Haematol 1996;95:21-6.  Back to cited text no. 4
    
5.
Kuter DJ. Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med 2009;60:193-206.  Back to cited text no. 5
    
6.
Dixon R, Rosse W, Ebbert L. Quantitative determination of antibody in idiopathic thrombocytopenic purpura. Correlation of serum and platelet-bound antibody with clinical response. N Engl J Med 1975;292:230-6.  Back to cited text no. 6
    
7.
McMillan R, Smith RS, Longmire RL, Yelenosky R, Reid RT, Craddock CG. Immunoglobulins associated with human platelets. Blood 1971;37:316-22.  Back to cited text no. 7
    
8.
Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. Blood 1946;1:27-50   Back to cited text no. 8
    
9.
Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood 2003;102:887-95.   Back to cited text no. 9
    
10.
Burrows RF, Kelton JG. Incidentally detected thrombocytopenia in healthy mothers and their infants. N Engl J Med 1988;319:142-5.  Back to cited text no. 10
    
11.
Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D. Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: A systematic review and meta-analysis. J Antimicrob Chemother 2007;60:237-46.  Back to cited text no. 11
    
12.
George JN, Saucerman S. Platelet IgG, IgA, IgM, and albumin: Correlation of platelet and plasma concentrations in normal subjects and in patients with ITP or dysproteinemia. Blood 1988;72:362-5.  Back to cited text no. 12
    
13.
Psaila B, Bussel JB. Refractory immune thrombocytopenic purpura: Current strategies for investigation and management. Br J Haematol 2008;143:16-26.  Back to cited text no. 13
    

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Correspondence Address:
Jyothis Purushothaman
Department of Transfusion Medicine, Jubilee Mission Medical College and Research Institute, Thrissur - 680 005, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-6247.177204

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