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

Microvascular thrombosis indicates a pathological occlusion of microvessels by fibrin- and/or platelet-rich thrombi. It is observed during systemic infections, cancer, myocardial infarction, stroke, neurodegenerative diseases and in thrombotic microangiopathies. Microvessel thrombosis can cause greatly differing symptoms that range from limited changes in plasma coagulation markers to severe multi-organ failure. Because microvessel thrombi are difficult to detect and often occur only transiently, their importance for disease development and host biology is likely markedly under-appreciated. Recently, clear indications for a biological basis of microvascular thrombosis have been obtained. During systemic infections microvessel thrombosis can mediate an intravascular innate immune response (immunothrombosis). This biological form of thrombosis is based on the generation of fibrin inside blood vessels and is critically triggered by neutrophils and their interactions with platelets which result in the release of neutrophil extracellular traps (extracellular nucleosomes). Immunothrombosis is critically supported by neutrophil elastase and the activator molecules of blood coagulation tissue factor and factor XII. Identification of the biological driving forces of microvascular thrombosis should help to elucidate the mechanisms promoting pathological vessel occlusions in both microvessels and large vessels.
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PMID:Biological basis and pathological relevance of microvascular thrombosis. 2475 39

Hyperdensity in the middle cerebral artery (MCA) or posterior cerebral artery (PCA) on non-contrast head CT, suggests the presence of a thrombus inside these vessels, often referred to as the "MCA sign" or "PCA sign" respectively. These two signs are classically associated with strokes secondary to cardiovascular etiologies and are only infrequently reported with other types of stroke. Whereas stroke is a recognized complication of pneumococcal meningitis hyperdense large vessel sign (in this case a combination of MCA and PCA) has not been previously reported. We report a case of rapidly progressive pneumococcal meningitis that presented as acute stroke involving large vessels in the vicinity of the circle of Willis in a patient with a history of non-Hodgkin lymphoma (NHL) in remission for 6 years. This patient had received a week of high dose steroids before admission. Head CT scan on admission showed the presence of hyperdense MCA and PCA signs. The patient rapidly deteriorated and a follow-up head CT revealed diffuse brain edema and increased density in the basal cisterns without evidence of sub arachnoid hemorrhage. Tc99m exametazime brain flow scan showed no intracerebral blood flow both supra and infratentorially. Steptococcus pneumoniae, NHL cells and high-dose steroid use can upregulate tissue factor synthesis and may have led to a hypercoagulable state via activation of the extrinsic pathway in the large intracerbral arteries.
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PMID:Hyperdense large artery sign in meningitis: A marker of ominous thrombogenic potential of pneumococcus? 2496 58

Sickle cell syndrome (SCS) includes a group of congenital hemolytic anemias associated to the presence of hemoglobin S, which is characterized by acute pain episodes and progressive damage of different organs. Some patients with sickle cell syndrome have shown, when compared with healthy individuals, an increased risk of presenting stroke, pulmonary hypertension, avascular necrosis of joints, acute chest syndrome and pregnancy complications, associated to a hypercoagulable state induced by alterations in different components of hemostasis, such as changes that include activation of the endothelium, platelet activity, coagulation and fibrinolytic systems. This paper compiles hemostasis disorders, associated with thrombotic manifestations, reported until now in sickle cell syndrom. These patients have an increase in activation markers of the coagulation system, such as prothrombin fragment 1.2, thrombin-antithrombin complex, etc., depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system and increased tissue factor expression. Similarly, abnormal expression of glycoproteins and increased adhesion and platelet aggregation have been reported. All these alterations produce a hypercoagulable state, which induces, among other things, the appearance of thrombotic complications. In view of the importance of controlling the different complications that can occur in patients with sickle cell syndrome, we recommend the implementation, in diagnosis and monitoring studies, of the evaluation of the different components of the hemostatic system, identifying alterations at an early stage and applying effective treatments to prevent thrombotic complications.
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PMID:[Hemostasis alterations in sickle cell syndrome]. 2497 33

Tissue factor (TF) is known to be the key element in the initiation of the extrinsic pathway of the coagulation cascade and appears to be a critical determinant of atherosclerotic plaque thrombogenicity. TF is needed to produce thrombin from prothrombin. In the extrinsic pathway, TF activates factor Vll. TF is expressed mainly on subendothelial tissues, but TF expression may be induced on endothelial cells by inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha). Subendothelial TF is responsible for initiating fibrin formation at sites of vascular injury, bloodborne TF may be an important contributor to propagation of the developing thrombus. It has been postulated that the blood-borne TF initiates the thrombogenic stimulus, leading to the formation of larger and more stable thrombus. TF may attach to cellular receptors, which in turn affect the production and release of inflammatory mediators. Baseline plasma TF activity has been demonstrated as an independent predictor for cardiovascular death in patients with acute myocardial infarction. TF is expressed by macrophage-derived foam cells in atherosclerotic plaques. TF levels were higher in atheroma from patients with unstable angina than with stable angina. These results suggest that high levels of TF exposed upon plaque rupture trigger atherothrombosis. Inhibition of TF would be expected to reduce thrombosis associated with a variety of diseases. TF pathway is a potential target for new therapeutic agents that can decrease TF activity, such as active site-inactivated factor VIIa, recombinant TF inhibitor and antibodies against TF or peptides interfering with TF-FVIIa complex activity. Significant clinical forms of atherosclerosis, such as sudden death, myocardial infarction, and stroke have common pathogenesis. The occlusion of the vessel lumen is the result from atherosclerotic plaque rupture/erosion that initiate thrombus formation. This thrombus has complex structure and contains predominantly fibrin in addition to platelets, suggesting an important role for the coagulation cascade in plaque thrombus formation. Tissue factor (TF) is known to be the key element in the initiation of the extrinsic pathway of the coagulation cascade and appears to be a critical determinant of atherosclerotic plaque thrombogenicity.
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PMID:Tissue factor and atherothrombosis. 2531 27

Atherosclerosis is a progressive disease characterized by the accumulation of lipids in medium to large sized arteries. Atherothrombosis is a term used to describe formation of a thrombus after rupture of an atherosclerotic plaque. Thrombosis can lead to myocardial infarction and stroke. Risk factors for atherosclerosis include hyperlipidemia, diabetes, smoking and hypertension all of which increase tissue factor (TF) expression. High levels of TF are present in atherosclerotic plaques due to expression by macrophages and vascular smooth muscle cells and the presence of cell-derived TF-positive microvesicles (MVs). In addition, hyperlipidemia leads to the formation of oxidized LDL, which induces TF expression in circulating monocytes and the release of TF-positive MVs. The major source of TF that drives thrombosis after plaque rupture is TF within the plaque. However, TF in the blood on monocytes and MVs may also contribute the thrombosis. Inhibition of the TF/factor VIIa complex is unlikely to be an effective strategy to reduce atherothrombosis due the essential role of the complex in hemostasis. However, selective blockade of pathologic TF without affecting protective TF may be effective in reducing atherothrombosis. For instance, statins have been shown to reduce TF expression in the plaque and in circulating monocytes, which would be expected to reduce thrombosis. Further studies are needed to determine safe strategies to reduce pathologic TF expression and atherothrombosis.
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PMID:Tissue Factor and Atherothrombosis. 2601 13

Recent studies have shown an association between thrombosis and factor VII (FVII), tissue factor (TF), and angiotensin-converting enzyme (ACE). This suggests that individuals with FVII-402 G/A, FVII-401 G/T, TF+5466 A/G, and ACE-287 insertion/deletion (I/D) polymorphisms present an increased risk of venous thrombosis, heart disease, and ischemic stroke compared with controls. In this study, we investigated the frequencies of these polymorphisms and their association with arterial and venous thrombosis. For the FVII-402 G/A polymorphism, there were 57.3% heterozygote (HT) genotypes and 8.3% homozygote (HM) genotypes in the patients, and 45.2% HT genotypes and 15.4% HM genotypes in the controls. For the FVII-401 G/T polymorphism, there were 37.5% HT genotypes and 3.1% HM genotypes in the patients, and 32.7% HT genotypes and 4.8% HM genotypes in the controls. The polymorphism TF+5466 A/G was not found in any of the samples analyzed. For the ACE-287 I/D polymorphism, there were 43 (40.6%) HT genotypes and 63 (59.4%) HM genotypes in the controls and 28 (45.2%) HT genotypes and 34 (54.8%) HM genotypes in the patients. No significant difference was observed by comparing patients and controls. In this study, no association was found between the presence of the evaluated polymorphisms and the occurrence of thrombotic events.
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PMID:Lack of association between potential prothrombotic genetic risk factors and arterial and venous thrombosis. 2634 91

Trousseau's syndrome is a well-known malignancy associated hypercoagulative state leading to venous or arterial thrombosis. The pathophysiology is however poorly understood, although multiple mechanisms are believed to be involved. We report a case of Trousseau's syndrome resulting in concomitant cerebral and myocardial microthrombosis, presenting with acute ischemic stroke and markedly elevated plasma troponin T levels suggesting myocardial injury. Without any previous medical history, the patient developed multiple cerebral infarctions and died within 11 days of admission. The patient was postmortem diagnosed with an advanced metastatic adenocarcinoma of the prostate with disseminated cerebral, pulmonary, and myocardial microthrombosis. Further analyses revealed, to the best of our knowledge for the first time in stroke patients, circulating microvesicles positive for the epithelial tumor marker CK18 and citrullinated histone H3 in thrombi, markers of the recently described cancer-associated procoagulant DNA-based neutrophil extracellular traps. We also found tissue factor, the main in vivo initiator of coagulation, both in thrombi and in metastases. Troponin elevation in acute ischemic stroke is common and has repeatedly been associated with an increased risk of mortality. The underlying pathophysiology is however not fully clarified, although a number of possible explanations have been proposed. We now suggest that unexplainable high levels of troponin in acute ischemic stroke deserve special attention in terms of possible occult malignancy.
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PMID:Trousseau's Syndrome, a Previously Unrecognized Condition in Acute Ischemic Stroke Associated With Myocardial Injury. 2642 12

Fibrinogen depletion via catalysis by snake venom enzymes as a therapeutic strategy to prevent or treat thrombotic disorders was utilized for over four decades, with ancrod being the quintessential agent. However, ancrod eventually was found to not be of clinical utility in large scale stroke trial, resulting in the eventual discontinuation of the administration of the drug for any indication. It was hypothesized that ancrod, possessing thrombin-like activity, may have unappreciated robust coagulation kinetics. Using thrombelastographic methods, a comparison of equivalent tissue factor initiated thrombin generation and Calloselasma rhodostoma venom (rich in ancrod activity) on plasmatic coagulation kinetics was performed. The venom resulted in thrombi that formed nearly twice as fast compared to thrombin formed clots, and there was no difference in fibrinolytic kinetics initiated by tissue-type plasminogen activator. In plasma containing iron and carbon monoxide modified fibrinogen, which may be found in patients at risk of stroke, the coagulation kinetic differences observed with venom was still more vigorous than that seen with thrombin. These phenomena may provide insight into the clinical failure of ancrod, and may serve as an impetus to revisit the concept of fibrinogen depletion via fibrinogenolytic enzymes, not those with thrombin-like activity.
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PMID:Ancrod revisited: viscoelastic analyses of the effects of Calloselasma rhodostoma venom on plasma coagulation and fibrinolysis. 2690 70

Vascular complications in patients with glioma most commonly include venous and arterial thromboembolism; however, treatment-induced vasculopathies are also problematic, especially in long-term survivors. The interactions between treatment such as radiation and chemotherapy, the coagulation cascade, endothelium, and regulators of angiogenesis are complex, drive glioma growth and invasion, and create common management problems in the clinic. We review the incidence of thrombotic complications in glioma, the biology of the coagulome as related to glioma progression, prevention and treatment of thrombosis, the role of anticoagulants as anticancer therapy, and vascular complications such as ischemic stroke and intracranial bleeding. The coagulation cascade is intimately involved in cancer-related thrombosis, glioma progression, and vascular complications of glioma therapy. Tissue factor is the principal initiator of coagulation and is upregulated in a glioma subtype-specific fashion. Short-term (perioperative) antithrombotic prophylaxis is effective, but long-term anticoagulation, although attractive, is not routinely indicated. Most patients with symptomatic venous thromboembolism can be safely anticoagulated, including those on anti-vascular endothelial growth factor therapeutics such as bevacizumab. Initial therapy should include low-molecular-weight heparin, and protracted anticoagulant treatment, perhaps indefinitely, is indicated. Many complex interactions resulting in vessel wall injury can lead to ischemic stroke, intracranial and intratumoral hemorrhage, and long-term sequelae such as cognitive impairment.
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PMID:Vascular complications in glioma patients. 2694 59

Tissue factor is the primary initiator of the coagulation cascade. Formation of the TF:FVIIa complex activates both FX and FIX, with subsequent thrombin generation, fibrin deposition and activation of platelets. In addition to playing important role in hemostasis and thrombosis, TF and downstream coagulation proteases can mediate intracellular signaling via activation of protease-activated receptors (PARs). Maintaining hemostasis in the brain is of utmost importance: bleeding or thrombosis within this organ can lead to significant morbidity and mortality. Both TF and PARs are widely expressed within the CNS, with TF expressed predominantly by astrocytes and PARs expressed in multiple cell types including astrocytes, neurons, microglia and oligodendrocytes [1-4]. PARs activation can result in either neuronal survival or death and link the coagulation system with the inflammatory response. In this brief review we summarize the contribution of the coagulation system to brain hemostasis as well as to the pathophysiology of stroke and multiple sclerosis.
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PMID:Astrocyte tissue factor controls CNS hemostasis and autoimmune inflammation. 2720 29


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