Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral blood flow is inversely related to in vitro whole blood viscosity, the major determinant of which is haematocrit. Haemodilution increases cerebral blood flow in polycythaemic patients and in subjects with high normal haematocrit. There is now increasing evidence that this relationship reflects a homeostatic and physiological regulation of oxygen-carrying capacity. A high normal haematocrit proves to be a weak risk factor for stroke whilst stroke risk is clearly related to the target haematocrit in patients treated for polycythaemia rubra vera. Whilst venesection remains accepted prophylactic treatment against stroke and other vaso-occlusive events in the latter case, no large scale trial has formally assessed the role of haematocrit reduction in patients with early manifestations of cerebrovascular disease like transient ischaemic attacks or in the early stages of multi-infarct dementia. There are theoretical reasons why a high haematocrit might have adverse effects on the cerebral circulation in the presence of vessel occlusion. Thus, flow and therefore oxygen delivery would become constrained by high viscosity (haematocrit) in the maximally dilated ischaemic vascular bed, and secondary thrombosis would be encouraged by low flow rates, and increased cell-cell interaction. These arguments have led to two large multicentre clinical trials of haemodilution in acute stroke victims. Neither has revealed any clinical benefit in the treated group. The reasons for the failure of the trials are discussed. It is envisaged that haemodilution, as well as retaining a clinical role in the prevention of stroke in patients with polycythaemia, may be used as an adjunct to other therapy for the immediate sequelae of cerebral ischaemia.
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PMID:Influence of haematocrit in the cerebral circulation. 270 70

Polycythemia rubra vera (PRV) is a rare haematological disorder that has a high risk of stroke, although the pathophysiological origin of the cerebral ischaemia in this disease is not well known. We report a case of a stroke patient with PRV in whom bilateral embolic signals were detected by transcranial Doppler (TCD). Cerebral computed tomography showed a cortical middle cerebral artery infarction, echocardiography was normal, duplex-scan showed moderate left carotid stenosis and digital angiography disclosed right siphon stenosis. TCD examinations in the acute phase repeatedly showed a great number of bilateral microembolic signals (MESs). Four months later magnetic resonance angiography showed no flow signal in the right siphon and a severe stenosis of the proximal right MCA. The detection of bilateral MESs in the absence of cardiac sources of embolism observed in this patient suggests that ischaemic cerebral events in PRV may have an embolic origin favoured by a prothrombotic state.
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PMID:Cerebral embolism in a patient with polycythemia rubra vera. 1080 20

Polycythemia vera (PV) can produce cerebral infarction. The mechanisms proposed by most authors are hyperviscosity-related diminished cerebral blood flow and platelet function abnormalities. We present a 36-year-old woman whose initial clinical manifestation of PV consisted of cerebral ischemia due to a carotid thrombus, as well as occlusion of the middle cerebral artery and cortical branches of the anterior cerebral artery demonstrated by angiography. To our knowledge, this is the first published case of cerebral infarction in PV caused by a thrombus of an extracranial artery. Therefore, PV can produce ischemic stroke due to thrombosis not only in small distal arteries or arterioles but also in the carotid artery or main branches. Treatment of intraluminal thrombus in non-arteriosclerotic carotid artery is discussed. Myeloproliferative disorders, including PV, must be suspected in all stroke patients with an elevated platelet count, even in those who have potential causes of reactive thrombocytosis.
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PMID:[Carotid thrombus and cerebral infarction as the initial clinical manifestation of polycythemia vera]. 1589 49

The role of genetic mutations in cerebral ischemia is not completely understood. Among these genetic variations, Philadelphia-negative gain-of-function mutation in the janus kinase 2 (JAK2) protein leads to overexpression of the genes involved in cell growth and proliferation, and has been linked to development of hematological malignancies, specifically, myeloproliferative neoplasms (MPNs; essential thrombocythemia [ET], polycythemia vera [PV], and primary myelofibrosis). Overt ET and PV are known to induce a prothrombotic state that leads to development of vascular complications, including cerebral arterial or venous thrombosis. Thromboembolism can precede overt presentation of an MPN by 2-3 years. As such, for the selected cases of embolic stroke or cerebrovascular sinus thrombosis with otherwise undetermined source and persistent thrombocytosis or polycythemia, in the absence of a confirmed MPN diagnosis, screening for JAK2 mutation may be reasonable, as early diagnosis and appropriate treatment can influence outcome by preventing recurrent thrombotic events. In this article, we review the literature on the genetics, pathogenesis, clinical manifestations, and treatment of JAK2-associated thrombosis, and present 2 cases of JAK2-associated cerebral arterial infarction and cerebral and systemic venous thromboembolism with otherwise negative etiology workup for stroke.
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PMID:Implications of Janus Kinase 2 Mutation in Embolic Stroke of Unknown Source. 3005 70