Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by isolated overproduction of platelets, thrombohemorrhagic complications, and a median age of 50-60. When it occurs in younger patients, the incidence of complications has been reported to be quite low, with a good long-term prognosis. We report a retrospective review of 13 patients with ET between the ages of 22 and 35 in which 11 were symptomatic at diagnosis, with only one remaining asymptomatic during follow-up. Three patients presented with potentially life-threatening complications (two myocardial infarctions, one stroke), although no deaths were observed. The majority of the nonlife-threatening complications were vaso-occlusive in nature, including erythromelalgia and transient neurologic symptoms. We conclude that ET in young adults is not always a benign disease and that potentially life-threatening complications are not rare. The optimum approach to treatment in this or any other age group remains uncertain.
 ...
PMID:Clinical manifestations of essential thrombocythemia in young adults. 229 60

Essential thrombocytemia (ET) is a clonal myeloproliferative disorder of unknown cause, characterized by an increased number of apparently normal platelets. It has been related to a large number of mild ischemic complications, but rarely to acute stroke associated with documented large vessel thrombosis. We report the cases of 6 patients with acute ischemic stroke associated with ET (4 men and 2 women; mean age 61.7: range 49-78 years). The diagnosis of ET followed the onset of the stroke. The number of platelets was never greatly increased at the time of the stroke, and two patients presented no major risk factors for stroke. The involvement of the posterior circulation was observed in three patients, that of the anterior circulation in two patient and that of the border territory in one. The obstruction of large intracranial or extracranial vessels was detected in all of the patients, and all of them were treated with antiplatelet agents (aspirin or ticlopidine). The outcome was good in 3 patients, fair in one and bad in two. We retain that ET might be a cause of acute ischemic stroke as a result of large vessel obstruction.
 ...
PMID:Essential thrombocytemia and ischemic stroke: report of six cases. 769 94

Essential thrombocythemia (ET) is a rare, chronic myeloproliferative disorder of unknown origin characterized by thrombocytosis, excessive megakaryocytes, hemorrhages, and thrombotic complications. Because of the high costs of care for persons with rare diseases, policymakers are concerned with both clinical effectiveness and cost-effectiveness of new treatments. Although the clinical efficacy of all new pharmaceutical agents for rare diseases is evaluated extensively in clinical trial settings before approval by the Food and Drug Administration (FDA), comparative phase III trials of a new agent with its major competitor are sometimes not possible to carry out, and estimates of cost-effectiveness are therefore difficult to obtain. We describe methodologic issues associated with the development of economic models of new pharmaceutical agents for rare diseases and illustrate these issues with an analysis of a new therapy for ET. Anagrelide is a newly approved platelet aggregation inhibitor that can be used as primary therapy for ET. The agent reduces platelet counts by 50% in more than 70% of ET patients. Economic models suggest that, over the first year of anagrelide therapy, monthly costs for therapy and complications decreased from $775 to $490, the effectiveness improved to 98%, and the cost-effectiveness improved to $1,505 per major complication (gastrointestinal bleed, transient ischemic attack or stroke, or preinfarction angina or myocardial infarction) prevented. Sensitivity analyses indicate that, after the first 3 months of treatment, total costs of anagrelide treatment were in the range of $1,505 to $1,615 per major complication prevented. To make well-informed therapeutic decisions, policymakers and physicians require head-to-head studies of a new pharmaceutical agent with its major competitor. However, economic models can be used to derive estimates of cost-effectiveness of new pharmaceutical agents when such data are lacking. The interpretation of these models raises general issues related to the perspective of the investigator, study design, estimation of costs of care, rates of response, toxicity, survival, and the ability to generalize the results to other settings, as well as methodologic issues that are unique to rare diseases. If a comparative study found better therapeutic outcomes, then cost-effectiveness models would be of limited usefulness. Almost all physicians would use the drug with the better therapeutic profile.
 ...
PMID:Cost-effectiveness model of a phase II clinical trial of a new pharmaceutical for essential thrombocythemia: is it helpful to policy makers? 993 May 55

Low-risk essential thrombocythemia patients include patients aged 18 to < 80 years with no vascular risk factor or previous thrombosis, no associated disease, a normal life expectancy, and a platelet count between 400 and 1,000 x 10(9)/L up to 1,500 x 10(9)/L. Asymptomatic essential thrombocythemia patients may be at risk for microvascular circulation disturbances. The indication for low-dose aspirin in asymptomatic essential thrombocythemia patients is uncertain, therefore randomization for aspirin 50 mg versus placebo is recommended. Symptomatic essential thrombocythemia patients with erythromelalgia and its ischemic complications, atypical transient ischemic attacks, minor stroke, visual disturbances and "superficial thrombophlebitis" in the absence of bleeding, vascular risk factors, or vascular disease have a clear indication for aspirin in a regular dose. To determine whether 50 mg/day is as effective as 100 mg/day for the prophylaxis of microvascular circulation disturbances in essential thrombocythemia, a randomized trial comparing low-dose aspirin 50 mg versus 100 mg at platelet counts between 400 and 1,000 up to 1,500 x 10(9)/L is recommended. To address the question whether reduction of the platelet count to normal (< 350 x 10(9)/L) is as effective as low-dose aspirin for the long-term relief of microvascular circulation disturbances, a randomized study comparing low-dose aspirin with the correction of platelet count to normal by anagrelide is recommended. High-risk essential thrombocythemia patients have a clear indication for platelet reductive therapy, including: (a) platelets > 1,500 x 10(9)/L, history of major thrombosis (myocardial infarction, stroke, peripheral occlusive vascular disease), or presence of vascular disease (e.g., arteriosclerosis); (b) history or presence of spontaneous or major bleedings, bleedings elicited by low-dose aspirin for the secondary prevention of vascular complications in essential thrombocythemia at platelet counts < 1500 x 10(9)/L, and side effects of long-term aspirin treatment such as gastritis; and progression from low- to high-risk essential thrombocythemia patients during follow-up or progressive myeloproliferative disease such as significant splenomegaly, myelofibrosis, leukocytosis, etc. To address the question of optimal treatment of high-risk essential thrombocythemia patients, randomization for anagrelide versus interferon at < 65 years of age and anagrelide versus hydroxyurea at an age > 65 years is recommended.
 ...
PMID:Aspirin and platelet-lowering agents for the prevention of vascular complications in essential thrombocythemia. 1072 22

Polycythemia rubra vera (PRV) is a rare myeloproliferative disorder with a high risk of ischemic stroke. Although thrombosis of large cerebral arteries is the most frequently presumed pathomechanism, various infarct patterns have been described in patients with PRV and ischemic stroke. We report two patients with mild acute ischemic strokes and known PRV, in whom a scattered lesion pattern was detected by diffusion-weighted magnetic resonance imaging (DWI), but was not visible on computed tomography (CT) and conventional magnetic resonance imaging (MRI). Further diagnostic work-up including extra- and transcranial Doppler sonography (ECD, TCD), transesophageal echocardiography (TEE), magnetic resonance angiography and Holter monitoring revealed no obvious sources of cerebral embolism in both cases. However, TEE in one patient demonstrated spontaneous echo contrast (SEC) in the left atrium. In both patients the symptomatology resolved completely. The detection of a scattered infarct pattern by DWI in patients with PRV and acute ischemic stroke has not been reported previously. DWI findings together with the SEC in one patient emphasize the assumption that a prothrombotic state with subsequent arterial embolism rather than local arterial thrombosis may be the underlying pathomechanism of stroke in some patients with PRV. Adding DWI to the diagnostic work-up may help to clarify etiology in patients with PRV and acute ischemic stroke.
 ...
PMID:Diffusion-weighted magnetic resonance imaging in two patients with polycythemia rubra vera and early ischemic stroke. 1132 38

Hereditary prothrombotic states of clinical importance include factor V Leiden, the prothrombin 20210A mutation, deficiencies of protein C, protein S, or antithrombin, sickle cell disease, and hyperhomocysteinemia. Major acquired prothrombotic states include cancer, myeloproliferative disorders, the antiphospholipid syndrome, and heparin-induced thrombocytopenia. Because most of the hereditary prothrombic states are not established risk factors for arterial thrombosis, routine laboratory testing in most patients with ischemic stroke should be limited to complete blood count, lupus anticoagulant, anticardiolipin antibodies, and plasma total homocysteine. Additional testing for factor V Leiden, prothrombin 20210A, antithrombin, protein C, and protein S may be indicated for patients under the age of 50 or those with paradoxical cerebral embolism. The treatment of acute ischemic stroke in patients with prothrombotic states is similar to that in patients without an identifiable prothrombotic condition, and may include antiplatelet agents, anticoagulants, or thrombolytic therapy in patients who otherwise meet eligibility criteria. The potential benefit of chronic anticoagulation therapy for the primary or secondary prevention of stroke in patients with prothrombotic states has not been addressed in controlled clinical trials. Specific therapeutic approaches for the prevention of stroke are established for patients with sickle cell disease, myeloproliferative disorders, and heparin-induced thrombocytopenia, and are under investigation for hyperhomocysteinemia and the antiphospholipid syndrome.
 ...
PMID:Prothrombotic States that Predispose to Stroke. 1235 68

In the last few years there has been a marked increase in the recognition of patients who are potentially at risk of arterial occlusive events during pregnancy. This includes patients with a previous history of arterial occlusion such as myocardial infarction and stroke, patients known to carry acquired or inherited thrombotic risk factors including sickle cell and myeloproliferative disorders, and patients with prosthetic heart valves. This review details the management options for prevention of arterial occlusions in these at-risk patients and outlines potential management strategies for arterial occlusions occurring during pregnancy.
 ...
PMID:Prevention and treatment of arterial thrombosis in pregnancy. 1270 18

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.
 ...
PMID:[Carotid thrombus and cerebral infarction as the initial clinical manifestation of polycythemia vera]. 1589 49

Essential thrombocythaemia (ET), the most often occurring myeloproliferative disorder is a clonal malignant disorder arising from stem cell. The course of the disease is complicated by some severe thrombotic events and far less commonly by haemorrhagic phenomena. Treatment of ET consist of antiplatelet drugs (e.g. aspirin) and lowering platelet count (hydroxyurea or interferon alpha). Anagrelide (anagrelide hydrochloride) is an imidazoquinazoline derivative which lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet aggregation. The aim of the study was to evaluate the efficacy and side effects of anagrelide in patients with ET refractory to prior treatment with hydroxyurea. Anagrelide (Agrylin or Thromboreductin) was used in 40 patients with ET from Jan. 1999 to June. 2003. Out of 40 patients, there were 29 females and 11 males, (median age 52.0 +/- 14.25 years; range, 21-72). Median follow up was 23 months (range, 8 to 54 months). Anagrelide in the average dose of 2,0 mg (range, 1,0-3,5 mg) reduced platelet count in all patients. Median time of response was 3-4 weeks. Complete remission (platelet count < or =450 G/l) achieved 22 persons (55%) and partial remission 17 persons, and only one patient had platelet count slightly above 600 G/l (627 G/l). There was a significant (p < 0.05) reduction in platelet count from a mean of 1136.05 +/- 295.09 G/l to 480.98 +/- 72.26 G/l (56%) Despite platelet count reduction <500 G/l in 3 patients reappeared symptoms of low extremities deep venous thrombosis and in one transient ischaemic cerebral stroke was found. Hemoglobin level in a single case was lower than 12 g/dL (10.8 g/dL), and neither leukopenia nor disturbances of hepatic or renal function were observed. During the first two months of treatment with anagrelide some mild and transient side effects were noticed, eg. headache in 10 (25%), fluid retention in 8 (20%), palpitations in 4 (10%), and diarrhoea in 2 (5%) patients, but all of them continued therapy. Achieved platelet count reduction allowed in 2 ET patients safe performance of planned surgery (cholecystectomy, partial thyroidectomy) and in 1 balloon coronary angioplasty. Anagrelide proved to be an effective drug for of ET patients refractory to hydroxyurea.
 ...
PMID:[Anagrelide in the treatment of thrombocythemia essential (ET)]. 1596 9

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.
 ...
PMID:Anagrelide: a review of its use in the management of essential thrombocythaemia. 1639 70


1 2 3 Next >>