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

Thrombotic disorders and their common clinical phenotypes of acute myocardial infarction, ischemic stroke, and venous thromboembolism are the proximate cause of substantial morbidity, mortality, and health care expenditures worldwide. Accordingly, therapies designed to attenuate thrombus initiation and propagation, reflecting integrated platelet-mediated and coagulation protease-mediated events, respectively, represent a standard of care. Unfortunately, there are numerous inherent limitations of existing therapies that include target nonselectivity, variable onset and offset of pharmacodynamic effects, a narrow efficacy-safety profile, and the absence of a safe and reliable platform for either accurate titration, based on existing patient-specific, disease-specific, and clinical conditions, or active reversibility. Herein, we summarize our experience with oligonucleotide antithrombotic agents and their complementary antidotes, targeting the platelet adhesive protein von Willebrand factor and the pivotal coagulation protease factor IXa.
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PMID:Antidote-controlled antithrombotic therapy targeting factor IXa and von Willebrand factor. 1979 78

Thrombus formation at a site of arterial injury (eg, rupture of an atherosclerotic plaque in a carotid artery), a crucial step in the pathogenesis of cerebral ischemia, is initiated by the adhesion of platelets to the arterial wall. In vivo, activated platelets release adenosine diphosphate (ADP), whose binding to the platelet P2Y12 receptor elicits progressive and sustained platelet aggregation. As a result, this receptor has been a target for the development of clinically effective antiplatelet agents, such as the thienopyridines ticlopidine and, more recently, clopidogrel, the only two currently FDA-approved P2Y12 antagonists. Clopidogrel has a well-established role as an antithrombotic agent in the setting of ischemic stroke. However, several challenges remain, including the relatively slow onset of action of this drug and the phenomenon of clopidogrel response variability or "resistance". A number of novel P2Y12 antagonists are therefore under investigation to determine whether they can result in better or more rapid antithrombotic effects than clopidogrel, without an unacceptable increase in hemorrhagic (or other) side effects. These include 1) prasugrel, an orally-administered thienopyridine prodrug, 2) ticagrelor (AZD6140), an ATP analog reversible P2Y12 antagonist, 3) cangrelor, an intravenously-administered reversible P2Y12 antagonist, and 4) PRT060128. Whether the promising pharmacological profile of these drugs will be translated into clinical benefit for stroke patients will be determined by the results of clinical trials.
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PMID:Advances in antiplatelet therapy for stroke prevention: the new P2Y12 antagonists. 2021 Jul 60

Elevated white blood cell count has recently been established as an independent risk factor for thromboembolic events in patients with myeloproliferative syndromes. Thrombotic events occur frequently in patients with haematological malignancies undergoing intensive cytoreductive treatment. We evaluated retrospectively the association of leukocyte counts and thrombosis in three cohorts of 100 patients each undergoing autologous or allogeneic haematopoietic stem cell transplantation or chemotherapy, respectively. A total of 26 thromboembolic events were recorded, 10 in recipients of allogeneic transplants, five in autografted patients, and 11 in the chemotherapy group. Fifteen events were central venous catheter related. Non-catheter related thrombotic events were pulmonary embolism (N=5), hepatic veno-occlusive disease (N=2), deep-vein thrombosis (N=1), stroke (N=1), ovarian vein thrombosis (N=1), and left ventricular thrombosis (N=1). Hazard rates showed two peaks, a first during cytoreduction in all groups, and a second after engraftment in transplanted patients. Time-dependent multivariable Cox analysis confirmed an association of leukocytosis with development of thrombosis (hazard ratio for leukocyte count > 11G/l: 9.73, 95% confidence interval 1.98-47.9, p=0.005). The risk associated with leukocytosis was independent from C-reactive protein level. Thrombocyte count and type of treatment (allogeneic vs. autologous transplantation vs. chemotherapy) had no significant influence on thrombosis development. In three cohorts of patients undergoing intensive cytoreductive treatment for haematological malignancy, leukocyte count was strongly associated with development of thrombotic complications.
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PMID:Leukocyte count and risk of thrombosis in patients undergoing haematopoietic stem cell transplantation or intensive chemotherapy. 2035 61

The presence of antiphospholipid antibodies has been shown to be related to an increased risk of thrombotic events. In patients with definite antiphospholipid syndrome (APS), that is, those who have had thrombosis and at least two positive determinations of antiphospholipid antibodies, secondary thromboprophylaxis with long-term anticoagulation therapy results in a low rate of recurrent thrombotic events, ranging from 0.016 to 0.031 events per patient per year. Thrombotic complications are, however, the most common cause of death in APS. The mortality rate in a large European cohort of patients with APS during a 5-year study period was 5.3%, and up to 40% of the deaths in this cohort were attributed to severe thrombotic events such as myocardial infarction, stroke and pulmonary embolism. Catastrophic APS is an unusual form of the disease, being observed in less than 1% of reported cases of APS, which is associated with a much higher mortality rate than classical APS. The combined use of anticoagulation, corticosteroids, plasma exchange and intravenous immunoglobulin therapy could result in a dramatic reduction in mortality, by approximately 20%, in patients with catastrophic APS.
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PMID:Antiphospholipid syndrome: frequency, main causes and risk factors of mortality. 2038 63

Thrombus formation in a disrupted endothelium is influenced not only by the platelet redox state and reactive oxygen and nitrogen species but also by the presence of endogenous or exogenous antioxidants. Thrombus formation in the stenotic arteries is triggered predominantly by attenuated shear stress. Superoxide and nitric oxide production, as well as their metabolism, potentially influence platelet activation and thrombosis. Antioxidant supplementation has not been generally associated with better cardiovascular outcome and is often compounded by bleeding and hemorrhagic stroke. Because of recent developments like the human genome project and personalized medicine, an emerging new area of nutrigenomics and nutraceuticals offers a scientific approach of diet-based therapeutics applicable to a plethora of human diseases, including cardiovascular inflammation and thrombosis. Therefore, further mechanistic research using nutragenomics and nutraceuticals in the prevention and management of thrombosis offers great potential and may be effective in limiting the problems associated with antioxidant-based therapeutics. In the present review, we have summarized the effect of dietary antioxidants in the modulation of platelet-mediated thrombosis. In addition, therapeutic opportunities in the area of nutragenomics and nutraceuticals in vascular and nonvascular diseases are also discussed.
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PMID:Review: Nutriceuticals as antithrombotic agents. 2055 90

Thrombotic manifestations occurring in patients with coagulation defects have drawn considerable attention during the last decade. It concerned mainly patients with hemophilia, vW disease or FVII deficiency. Occasional reports involved also the deficiencies of the contact phase of blood coagulation, mainly FXII deficiency. The purpose of the present study was to evaluate the comparative incidence of thrombosis in all reported patients with FXII, Prekallikrein and Kininogens deficiencies. Out of the reported 341 cases with these conditions that could be tracked there were 43 cases with thrombosis. More specifically, there were 32 patients with FXII deficiency who also had a thrombotic event (16 arterial and 16 venous). As far as Prekallikrein deficiency is concerned, there were nine cases with thrombosis (five arterial and four venous). Finally, two patients with Total or High molecular weight Kininogen deficiencies had also a thrombotic manifestation (one arterial and one venous). The thrombotic manifestations were M.I. 11 cases; ischemic stroke 9 cases; peripheral arteries 3 cases; deep vein thrombosis with or without pulmonary embolism 17 cases; thrombosis in other veins 3 cases. Congenital or acquired associated prothrombotic risk factors were present in 33 out of 36 cases. In three cases the existence of associated risk factors was excluded whereas in the remaining seven patients no mention is made in this regard. This study clearly indicates that the severe in vitro coagulation defect seen in these conditions does not protect from thrombosis.
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PMID:Comparative incidence of thrombosis in reported cases of deficiencies of factors of the contact phase of blood coagulation. 2057 81

Thrombus formation is complex process involving both cellular and molecular (protein) components. Platelets are responsible for maintaining hemostasis and for preventing excessive bleeding. These cells aggregate along with other plasma components and blood cells to form blood clots. Undesirable platelet aggregation may lead to life-threatening conditions such as stroke. Thrombogenicity is the property of a material to induce the formation of a thrombus, which results in partial or complete occlusion of a blood vessel. The tendency to cause platelet aggregation and perturb plasma coagulation can serve as an in vitro measure of a nanomaterial's likelihood to be thrombogenic in vivo. This chapter describes a procedure for in vitro analyses of platelet aggregation and plasma coagulation time. Platelet-rich plasma (PRP) is obtained from freshly derived human whole blood and incubated with nanoparticles. Then the plasma is examined using a particle count and size analyzer to determine the number of active platelets. The percent aggregation is calculated by comparing the number of active platelets in the nanoparticle-exposed sample to control plasma. To measure the plasma coagulation time, platelet-poor plasma from human whole blood is exposed to nanoparticles in vitro and analyzed in prothrombin (PT), activated partial thromboplastin (APTT), and thrombin time assays.
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PMID:Method for in vitro analysis of nanoparticle thrombogenic properties. 2111 72

A 77-year old man experiencing frequent transient ischemic attacks for five days was admitted to our hospital. Radiological examinations including brain computed tomography, supraaortic computed tomography angiography were performed. Supraaortic computed tomography angiography revealed two thrombi in common carotid artery. Thrombi were located proximally, one of which was elongated and adhared to the arterial wall and the other one was located below bifurcation of left carotid artery. Since the case has been categorized as a high risk patient for ischemic stroke despite the normal neurological status, intravenous recombinant tissue plasminogen activator was given. Ischemic attacks completely ceased soon after thrombolysis. Control computed tomography angiography revealed normal findings with patent carotid artery, without any clot. To our knowledge this is the only case of transient ischemic attack treated with intravenous recombinant tissue plasminogen activator in the literature with the score of 0 on the National Institutes of Health Stroke Scale.
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PMID:Intravenous thrombolytic treatment in a patient with transient ischemic attack associated with mural carotid thrombi. 2135 83

Diabetic ketoacidosis (DKA) is a state of severe insulin deficiency, either absolute or relative, resulting in hyperglycemia and ketonemia. Although possibly underappreciated, up to 10% of cases of intracerebral complications associated with an episode of DKA, and/or its treatment, in children and youth are due to hemorrhage or ischemic brain infarction. Systemic inflammation is present in DKA, with resultant vascular endothelial perturbation that may result in coagulopathy and increased hemorrhagic risk. Thrombotic risk during DKA is elevated by abnormalities in coagulation factors, platelet activation, blood volume and flow, and vascular reactivity. DKA-associated cerebral edema may also predispose to ischemic injury and hemorrhage, though cases of stroke without concomitant cerebral edema have been identified. We review the current literature regarding the pathogenesis of stroke during an episode of DKA in children and youth.
Stroke Res Treat 2011 Feb 22
PMID:Diabetic ketoacidosis-associated stroke in children and youth. 2142 57

Acute compartment syndrome is a life-threatening complication in trauma patients. Not only regional neuromuscular disability, but also systemic organ disorders can result from prolonged tissue ischemia. In this report, we describe 2 cases of acute atraumatic compartment syndrome complicated with severe heat stroke. In both cases, emergency fasciotomy was rapidly performed after recognition of the syndrome, but serious regional neuromuscular disabilities remained. Microvascular endothelial injury is an important mechanism of acute atraumatic compartment syndrome. Thrombi diffusely formed in the compartmental space hinder establishment of reperfusion even after fasciotomy. Furthermore, disruption of fibrinolysis due to heat stroke could enhance this damage.
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PMID:Two cases of acute atraumatic compartment syndrome complicated with severe heat stroke. 2150 13


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