Essential Thrombocytopenia/JAK Mutation Causing Thrombosis: A Case Report and Review of Literature

Case Report

J Blood Disord. 2015;2(1): 1021.

Essential Thrombocytopenia/JAK Mutation Causing Thrombosis: A Case Report and Review of Literature

Paolo Costa1, Michele Frigerio2, Elisabetta Del Zotto1, Alessia Giossi3, Irene Volonghi1, Loris Poli1, Andrea Morotti1, Valeria De Giuli1, Roberto Gasparotti2, Alessandro Padovani1 and Alessandro Pezzini1*

1Department of Clinical and Experimental Sciences, Clinical Neurology, University of Brescia, Italy

2Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Italy

3Neurology Unit, Hospital of Cremona, Cremona, Italy

*Corresponding author: Alessandro Pezzini, Department of Clinical and Experimental Sciences, Clinical Neurology, University of Brescia, P.le Spedali Civili, 1, 25123 Brescia, Italy.

Received: December 10, 2014; Accepted: January 27, 2015; Published: February 10, 2015


Classic Myeloproliferative Neoplasms (MPNs) include Polycythemia Vera (PV), Essential Thrombocythemia (ET), Chronic Myeloid Leukemia (CML) and Primary Myelofibrosis (PMF). Among these Chronic Myeloproliferative Disorders (CMPDs), ET can be diagnosed by the presence of a chronic nonreactive thrombocythemic state and by the exclusion of the other CMPDs. Similar to other CMPDs; ET can lead to vascular events through quantitative and qualitative changes of the affected hematologic cell. The disease can present with any subtype of stroke including Cerebral Vein Thrombosis (CVT), which although rarely, may complicate, proceed, and occur at the moment of this CMPD. We present the case of a 65-year-old female affected by CVT complicated by ischemic stroke with haemorrhagic transformation. After detection of JAK2 V617F mutation, the patient was diagnosed with Essential Trombocythemia (ET). We discuss the relationship between MPNs, focusing on ET, and cerebrovascular disease, the possible mechanisms linking the two conditions, and the different clinical features regarding stroke subtypes (both of arterial and venous origin). We also describe the clinical relevance of JAK2 V617F mutation and its role in the pathogenesis of thrombosis, ischemic stroke and CVT.

Keywords: Essential thrombocythemia (ET); Myeloproliferative neoplasms (MPNs); Stroke; Cerebral venous thrombosis (CVT); JAK2 V617F


BCSH: British Committee for Standards in Haematology; CVT: Cerebral Venous Thrombosis; SVT: Splanchnic vein thrombosis; ET: Essential Thrombocythemia; MPNs: Myeloproliferative Neoplasms; PLTS: Platelets; PV: Policythemia Vera; PMF: Primary Myelofibrosis; RBCS: Red Blood Cells

Case Presentation

A 65-year-old female was admitted to the emergency department for acute headache and delirium. She had no previous history of stroke or chronic diseases and was not assuming any medication. On admission, she showed a decreased level of consciousness and no other neurological signs. General examination was unremarkable. Routine laboratory exams were negative. Brain CT scan showed a temporo-parietal lesion consistent with an ischemic stroke complicated by haemorrhagic transformation with associated subarachnoid haemorrhage and mass effect (Figure 1, A-B). Digital subtraction cerebral angiography revealed enlargement of the cortical veins and acute right transverse sinus thrombosis (Figure 1, C-D). A diagnosis of Cerebral Vein Thrombosis (CVT) was done and the patient was treated with unfractionated heparin followed by oral anticoagulation. Before oral anticoagulation therapy was initiated, we performed an extensive screening for thrombophilic abnormalities including protein C deficiency, protein S deficiency, antithrombin III deficiency, the G20210A mutation in factor II gene, the G1691A mutation in factor V gene, anti-cardiolipin antibodies, anti-β2 glycoprotein I antibodies and lupus anticoagulant which was unremarkable. After improvement of the conscious state the neurological examination revealed sensory impairment in the left lower limb, left homonymous hemianopia and tactile neglect. The patient was discharged on oral anticoagulant therapy on day 27. One month after discharge, the patient experienced an acute pain in the left knee. Ultrasonographic examination revealed a thrombosis of the left popliteal vein, although the patient was still on oral anticoagulant therapy and within the therapeutic range. One year after the patient complained acute onset of sensory loss on the right side of the face associated with paresthesias, which resolved spontaneously in 2 hours. Symptoms were consistent with the clinical diagnosis of transient ischemic attack. Laboratory exams showed thrombocytosis (platelet count, 519,000/mm3). Blood count was otherwise normal. No iron deficiency was found. Molecular analysis of JAK2 gene was performed which revealed the JAK2 V617F mutation. Although the patient refused to undergo a bone marrow study, we diagnosed Essential Thrombocythemia (ET) according to the British Committee for Standards in Haematology (BCSH) diagnostic criteria (Table 1) [1,2], and started a long-term therapy with hydroxyurea, at an initial dose 15 mg/kg per day, then adjusted depending upon the balance between the desired effect on the PLT count. On subsequent evaluations we observed a regular course and follow up neuroimaging revealed no further complications. Laboratory, clinical and imaging findings are summarized in Table 2.