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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombosis is a major cause of mortality and morbidity in polycythemia vera (PV). The wide range of thrombotic events reflects the complex picture in PV. There are multiple factors involved in thrombogenesis in this disease, including increased hematocrit, thrombocytosis, impaired fibrinolytic activity, platelet activation, leukocyte activation, endothelial damage, interactions between platelets and endothelium, various modalities of therapy, and increased in whole-blood viscosity. Among them, the increase in blood viscosity, and hence the impairment of blood flow, is the major factor. In this article, the role of hyperviscosity in PV is reviewed. A high hematocrit occurs under PV and many other conditions with abnormal red blood cell aggregation. The impaired capillary blood flow results in neurological manifestations and increased bleeding risk in PV. Thrombotic complications can also occur in both arteries and veins and manifest as stroke, myocardial infarction, deep vein thrombosis, or pulmonary embolism. The hemodynamic principle is aptly applied in the management of PV. The most important objective is the reduction of the patient's hematocrit.
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PMID:Hyperviscosity in polycythemia vera and other red cell abnormalities. 1463 44

We report a patient with essential thrombocythemia (ET) who developed progressive occlusive cerebrovascular disease accompanied by ischemic events. A 40-year-old woman presented with an ischemic stroke in the territory of the left middle cerebral artery (MCA). Diagnostic work-up disclosed a moderate stenosis of the left carotid siphon and a mildly increased platelet count. Due to aspirin intolerance warfarin was administered. Twelve months later, ischemic strokes in the left MCA territory recurred. A left internal carotid artery occlusion at the origin was diagnosed. Bone marrow biopsy showed an increased number of megakaryocytes. Warfarin was replaced by clopidogrel. Cerebral artery obstructions remained unchanged during the next 3 years (six follow-up examinations); no further ischemic events occurred during that period, while mild thrombocytosis persisted. ET may be associated with progressive obstructions of large cerebral arteries; in our case, clopidogrel was effective in preventing recurrence of ischemic events.
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PMID:Progressive occlusive disease of large cerebral arteries and ischemic events in a patient with essential thrombocythemia. 1538 83

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

Platelets are formed and released into the bloodstream by precursor cells called megakaryocytes that reside within the bone marrow. The production of platelets by megakaryocytes requires an intricate series of remodeling events that result in the release of thousands of platelets from a single megakaryocyte. Abnormalities in this process can result in clinically significant disorders. Thrombocytopenia (platelet counts less than 150,000/microl) can lead to inadequate clot formation and increased risk of bleeding, while thrombocythemia (platelet counts greater than 600,000/microl) can heighten the risk for thrombotic events, including stroke, peripheral ischemia, and myocardial infarction. This Review will describe the process of platelet assembly in detail and discuss several disorders that affect platelet production.
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PMID:The biogenesis of platelets from megakaryocyte proplatelets. 1632 79

Anagrelide (Agrylin, Xagrid) is an oral imidazoquinazoline agent which is indicated in Europe for the reduction of elevated platelet counts in at-risk patients with essential thrombocythaemia who are intolerant of or refractory to their current therapy, and in the US for the reduction of elevated platelet counts and the amelioration of thrombohaemorrhagic events in patients with thrombocythaemia associated with myeloproliferative disorders. Anagrelide is well established as an effective platelet-lowering agent in most patients with essential thrombocythaemia, including both treatment-naive patients and those refractory to other cytoreductive therapy. Results of the only randomised trial to date (the Primary Thrombocythaemia 1 [PT1] study) indicated that the composite primary endpoint (arterial or venous thrombosis, serious haemorrhage or death from vascular causes) occurred more often in recipients of anagrelide plus aspirin than in those receiving hydroxycarbamide (hydroxyurea) plus aspirin. This trial also indicated that the incidence of the secondary endpoints transient ischaemic attack and gastrointestinal bleeding favoured hydroxycarbamide plus aspirin, while the incidence of venous thrombosis favoured anagrelide plus aspirin. There were no differences between the groups in the incidence of secondary endpoints myocardial infarction, stroke, unstable angina, pulmonary embolism, hepatic-vein thrombosis, other serious haemorrhage or related deaths. The design of the PT1 study has been queried with respect to the heterogeneous nature of the study population (possible inclusion of patients with early myelofibrotic disease) and the concomitant use of aspirin (interaction with anagrelide causing increased bleeding events). Further data are therefore required before the role of anagrelide in essential thrombocythaemia can be finalized. In the meantime, when considering treatment options for patients with this disorder, anagrelide's positive effects on platelet function, lack of mutagenicity and lack of association with leukaemia or angiogenesis must be balanced against its comparative expense and positive inotropic effects. Thus, the role of anagrelide in the management of high-risk patients with essential thrombocythaemia will ultimately depend on individual patient assessment and future clarification of the potential leukaemogenicity of hydroxycarbamide.
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PMID:Anagrelide: a review of its use in the management of essential thrombocythaemia. 1639 70

(1) For patients aged over 60 years who have essential thrombocythaemia, and are considered to be at increased risk of thromboembolism, the standard cytotoxic agent is hydroxycarbamide (hydroxyurea), which reduces the risk of thrombocytosis but adversely affects other blood cell lines. It may also increase the risk of progression to cancer. (2) Anagrelide, initially studied as an antiplatelet drug, was approved in Europe for the treatment of essential thrombocythaemia in high-risk patients when other treatments fail or are poorly tolerated. (3) Evaluation data includes a trial versus hydroxycarbamide that was prematurely halted because of an excess of cardiovascular events among patients on anagrelide. Among 809 patients who were also receiving aspirin as an antithrombotic (and who may not have met strict criteria for essential thrombocythaemia), arterial or venous thrombosis and haemorrhage were significantly more frequent with anagrelide, during a median follow-up of 39 months (55 versus 36 patients). (4) According to the results of 3 non comparative trials involving about 500 patients, and the European Medicines Agency report analysing these and other study populations, anagrelide reduces the platelet count to below 600 times 10 to the 9th power/litre in two-thirds of patients. No data are available on the clinical implications of this reduction in platelets. (5) Between 10% and 20% of patients treated with anagrelide experience cardiovascular adverse effects (palpitations, myocardial infarction, heart failure) or neurological adverse effects (headache, stroke, transient ischaemic attack). Gastrointestinal disturbances are also frequent (diarrhoea, nausea, abdominal pain, pancreatitis). Some of these adverse effects can be fatal. (6) Follow-up is too short to show whether anagrelide affects the risk of progression to cancer. (7) In practice, anagrelide has a less favourable risk-benefit balance than hydroxycarbamide, which remains the first-line cytotoxic agent in this setting. Anagrelide therapy can be considered if hydroxycarbamide fails or is poorly tolerated, provided patients are included in a long-term clinical trial.
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PMID:Anagrelide: new drug. Essential thrombocythaemia: further evaluation needed for this last-resort treatment. 1676 90

We describe an extremely rare case of megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. The patient had a very high platelet count and developed an ischemic stroke with seizures. She was treated with hydroxyurea, platelet apheresis, ARA-C, and idarubicin in order to obtain a prompt reduction of thrombocytosis and then with imatinib 600 mg/die PO. The therapy induced a complete hematological remission with a resolution of neurological signs within 4 weeks.
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PMID:Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. 1702 45

Children with sickle cell disease, a chronic hemolytic anemia, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, transient ischemic attacks, 'soft neurological signs', seizures, headache, coma, visual loss, altered mental status, cognitive difficulties, and covert or 'silent' infarction. Those with ischemic stroke usually have stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries. Indefinite transfusion prevents recurrence in most patients who have had a stroke, and can prevent first stroke in those with high transcranial Doppler velocities. High white cell count, low hemoglobin and oxyhemoglobin desaturation predict neurological complications. Other risk factors for overt ischemic stroke include hypertension, previous transient ischemic attack, covert infarction and chest crisis. For hemorrhagic stroke, aneurysms are common in adults but not children, who often present with hypertension after transfusion or corticosteroids. Seizures are particularly common in patients with cerebrovascular disease and covert infarction; the latter is also associated with hyposplenism and infrequent pain. Factors associated with cognitive difficulties include thrombocytosis, infarction, large-vessel disease, and perfusion abnormality on neuroimaging. As well as investigating the role of genes and the possibility that hydroxyurea or blood pressure control reduce neurological complications, we should explore the modifiable effects of poor nutrition, chronic infection, hemolysis and oxyhemoglobin desaturation on stroke risk.
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PMID:Therapy insight: stroke risk and its management in patients with sickle cell disease. 1747 74

Genetic and acquired disorders that foster a procoagulable state represent risk factors for stroke in childhood. Although an increased incidence of thromboembolic complications has been reported in patients with thalassemia, severe cerebral thromboembolism has rarely been observed in patients with beta-thalassemia minor. This article describes a case study of a 1-year-old boy who presented with left-sided hemiparesis, seizures, microcytic anemia, and recent infection with reactive thrombocytosis. Ischemic infarction in the territory of the right middle cerebral artery was confirmed by magnetic resonance imaging and magnetic resonance angiography. Genetic tests showed that the patient was heterozygous for the beta(degrees) -thalassemia IVS-I-1 mutation and homozygous for the methylentetrahydrofolate reductase C677T mutation. Based on these findings, it was concluded that the synergistic effects of multiple, genetic, and acquired prothrombotic risk factors brought about the hypercoagulable state that resulted in overt stroke in a thalassemic patient in early childhood.
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PMID:Arterial ischemic stroke in a child with beta-thalassemia trait and methylentetrahydrofolate reductase mutation. 1762 84

Inflammatory bowel disease has been linked to cerebrovascular lesions, but the mechanisms of these vascular complications and their frequency among children with inflammatory bowel disease are unclear. We present 4 children with inflammatory bowel disease who developed ischemic or hemorrhagic stroke or cerebral sinovenous thrombosis. All 4 patients were female; 3 had Crohn's disease and 1 had indeterminate colitis. All of the patients had additional risk factors for thrombosis including thrombocytosis, severe dehydration attributable to an inflammatory bowel disease exacerbation, and, in 2 instances, genetically mediated coagulation defects. It is believed that the occurrence of thrombotic complications in individuals with inflammatory bowel disease is attributable to multifactorial causes. The current literature on cerebrovascular complications and treatment in the setting of pediatric inflammatory bowel disease is reviewed.
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PMID:Inflammatory bowel disease and cerebrovascular arterial and venous thromboembolic events in 4 pediatric patients: a case series and review of the literature. 1818 42


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