A case of ischemic stroke with hemorrhagic transformation associated with essential thrombocythemia and JAK-2 V617F mutation

BACKGROUND: Essential thrombocythemia (ET) is a rare cause of stroke. The V617F mutation in the Janus kinase 2 (JAK2) gene is one of the most typical mutations in ET and has been shown to be a risk factor for stroke, especially in younger people. However, to date, there have been few reports of intracranial thrombotic and hemorrhagic complications in patients with ET. Herein, we present a case of JAK2 gene mutation-associated ET in a patient who developed both ischemic and hemorrhagic stroke, and discuss potential underlying mechanisms. CASE PRESENTATION: A 45-year-old Chinese male presented to our center with gradually developing weakness of the right limbs for 3 months. A computed tomography scan of the brain showed an area of infarction with hemorrhage in the left subcortical and corona radiata regions. High-resolution magnetic resonance imaging revealed a thrombosis on the surface of the atherosclerotic plaque. Digital subtraction angiography revealed an insect bite-like change in the C1 branch of the left internal carotid artery, which caused up to 50% stenosis. Blood tests showed continued elevation of the platelet and white blood cell counts. After consultation with a hematologist, a bone marrow biopsy was performed, which revealed proliferative bone marrow changes with numerous megakaryocytes and proliferative but mature granulocytes. Further genetic testing revealed a positive JAK2-V617F mutation. Therefore, the diagnosis of ET was confirmed according to the World Health Organization (WHO) 2016 diagnostic criteria. Finally, we decided to administer aspirin and hydroxyurea. The patient remained stroke free and the platelet levels were normal throughout the 1-year follow-up period. CONCLUSIONS: JAK2 mutations affect the proliferation and differentiation of blood cells through the JAK, signal transducer and activator of transcription pathway, which leads to changes in platelets and macrophages, and an increase in neutrophil extracellular traps, which may explain the patient’s ischemic and hemorrhagic changes. Further investigation of the underlying mechanisms may change the treatment strategy for such patients in the future.