LETTER TO THE EDITOR
|Year : 2016 | Volume
| Issue : 4 | Page : 532-533
Cerebral venous thrombosis in refractory idiopathic thrombocytopenia treated with eltrombopag
Vivek Nambiar1, TS Dhanya1, Neeraj Sidharthan2
1 Division of Stroke, Department of Neurology, Amrita Institute of Medical Sciences, Amrita Viswa Vidyapeetham University, Kochi, Kerala, India
2 Department of Hemato Oncology, Amrita Institute of Medical Sciences, Amrita Viswa Vidyapeetham University, Kochi, Kerala, India
|Date of Submission||06-Jun-2016|
|Date of Decision||16-Jun-2016|
|Date of Acceptance||16-Jun-2016|
|Date of Web Publication||21-Nov-2016|
Division of Stroke, B Block, Amrita Institute of Medical Sciences, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Nambiar V, Dhanya T S, Sidharthan N. Cerebral venous thrombosis in refractory idiopathic thrombocytopenia treated with eltrombopag. Ann Indian Acad Neurol 2016;19:532-3
|How to cite this URL:|
Nambiar V, Dhanya T S, Sidharthan N. Cerebral venous thrombosis in refractory idiopathic thrombocytopenia treated with eltrombopag. Ann Indian Acad Neurol [serial online] 2016 [cited 2019 Dec 7];19:532-3. Available from: http://www.annalsofian.org/text.asp?2016/19/4/532/194468
A 36-year-old lady, diagnosed with idiopathic thrombocytopenic purpura (ITP) for 5 years, presented with menorrhagia and a low platelet count of 5000/μL. She was on immunotherapy but with poor response, had splenectomy followed by a course of intravenous immunoglobulins. Her connective tissue and autoimmune work up for the evaluation of ITP were negative. On admission, she was started on thrombopoietin agonist (oral eltrombopag) in a dose of 50 mg/day. On day 3, she complained of mild holocephalic headache which gradually worsened in intensity, without any focal signs. Computed tomography (CT) imaging of the brain was unremarkable, and magnetic resonance (MR) imaging was planned.
However, after 48 hours of onset of headache, she developed sudden hemiparesis with fall at the hospital. Headache continued and she developed episodes of irrelevant talk. Urgent MR revealed venous infarct in the right frontal lobe with hemorrhagic transformation. MR venogram showed extensive thrombosis of the superior sagittal and transverse sinuses. The platelet counts gradually improved to 95,000/μL. Antiphospholipid antibodies levels and other antibodies were normal, and thrombophilia profile was negative. She was transferred to stroke service and admitted to the Intensive Care Unit, where the same night she developed status epilepticus. She was loaded with antiepileptic medications to control the seizures. Enoxaparin was started in a dose of 0.6 mg twice daily subcutaneously, meanwhile continuing the eltrombopag administration. Her headache resolved in 3 days, and there was improvement in left hemiparesis, and she was transferred to a rehabilitation facility.
Eltrombopag is a thrombopoietin-receptor agonist used as an effective treatment for ITP , as well as hepatitis C-associated thrombocytopenia. It is a nonpeptide ligand, binding the thrombopoietin receptor on megakaryocytes and platelets thereby enhancing the megakaryocyte production and platelet maturation. However, adverse effects of the agent include thrombotic episodes due to the release of platelet materials into the circulation.  The patient in discussion had no evidence of thrombosis before the administration of the drug. She developed extensive thrombosis following administration of the drug for 4 days. The prevalence of thrombotic episodes with eltrombopag in a randomized controlled trial was higher compared to the placebo group. Neurological deficits with arterial occlusions have also been reported with eltrombopag in the past. 
However, recently, there are also reports of paradoxical thrombosis in ITP that reveal prothrombotic tendencies in patients with ITP itself, which may also have contributed to the present condition.
The clinical scenario is challenging, especially in the background of severe ITP and low platelet counts. There is a possibility that one may suspect a bleed and order a CT brain to rule that out, missing an early underlying cerebral venous thrombosis. Here, the initial CT scan was normal with no typical features of cerebral sinus thrombosis. However, subsequent clinical deterioration led to MR brain and MR venogram. The diagnosis is important as the decision to anticoagulate is vital. The challenge after the diagnosis is the need for anticoagulation to be instituted in a brain with venous hemorrhagic infarct and low platelet count. The possibility of endovascular treatment should also considered, especially in patients with rapidly deteriorating neurological status. There are prior case reports of successful anticoagulation after thrombosis with eltrombopag.  The knowledge of thrombotic complications of this drug would help to detect early complications and initiate necessary management.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al.
Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237-47.
Dmytrijuk A, Robie-Suh K, Rieves D, Pazdur R. Eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura. Oncology (Williston Park) 2009;23:1171-7.
Mulla CM, Rashidi A, Levitov AB. Extensive cerebral venous sinus thrombosis following a dose increase in eltrombopag in a patient with idiopathic thrombocytopenic purpura. Platelets 2014;25:144-6.
Au WY, Ma ES, Chow PC, Kan YT. Sudden blindness due to bilateral central retinal artery occlusion in a patient on eltrombopag. Ann Hematol 2014;93:881-2.
Sanchez-Gonzalez B, Ancochea A, Garcia-Pallarols F, Jimenez C, Pedro C, Besses C. Feasible concomitant treatment with eltrombopag and oral anticoagulation in a patient with chronic immune thrombocytopenia and severe cardiac comorbidities. Platelets 2014;25:309-10.