Detection Of The Jak2-V617f Mutation In A Patient With Unexplained Strokes. Cinical Clues To Go Beyond The Conventional "Hypercoagulable Panel"

Background: Myeloproliferative diseases(MPD) are a group of diseases with increased proliferation of one or more subtypes of myeloid cells. There are three types of MPD: essential thrombocythemia, polycytemia vera , and primary myelofibrosis. JAK2-V617F mutation is an useful tool in the MPD diagnosis, The association of cerebrovascular diseases (CVD) secondary to the MPD has been stablished, whereas the indication for regular testing in patients with unexplained strokes remains unclear. The incidence of JAK2-V617F positive mutation in CVD has been analyzed in patients with ischemic strokes and cerebral venous thrombosis. Prior studies demonstrated a reasonable indication for JAK2-gene mutation testing in patients presenting with unexplained strokes associated to thrombocytosis, elevated hemoglobin and hematocrit (in absence of inherited or acquired thrombophilia). 18-53% of patients with prior splanchnic venous thrombosis and JAK2-V617F mutation suffered a latent MPD. Objective: To highlight the clinical presentation of a patient with prior splanchnic venous thrombosis and unexplained recurrent strokes as a guidance for the detection of JAK2-V617F mutation, hence the diagnosis of MPD. Patients and Methods: A 45 year-old woman with history remarkable for prior portal vein thrombosis at the age of 35,migraines with visual auras, patent foramen ovale; presents for evaluation of recent right middle cerebral artery territory infarct(s). On examination noticed malar rash, livedo reticularis and hepato-splenomegaly. Comprehensive work up excluded cardioembolic and autoimmune etiologies; an heterozygous MTHFR mutation was found in prior hypercoagulable evaluation. Results: Biallelic mutation of JAK2-V617F was detected. Conclusion: MPD should be suspected in patients with ischemic strokes and history of prior arterial/thrombotic events in absence of positive “conventional” hypercoagulable work up. In patients with history of ischemic stroke and prior splanchnic thrombosis, strongly suspect MPD and consider JAK2-V617F mutation testing.