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

Individuals vary considerably in their susceptibility to infection and in their ability to recover from apparently similar infectious processes. These differences can be partially explained by polymorphisms of the genes encoding proteins involved in mediating and controlling the innate immune response, the inflammatory cascade, coagulation, and fibrinolysis. It is evident from experimental studies that dysregulation of the coagulation system, which is characteristic of the pathophysiology of septic shock (a procoagulant and antifibrinolytic state), contributes to systemic inflammation and death in sepsis. Several genetic variations in proteins that increase coagulation or impair anticoagulation and fibrinolysis have been described. Thus, polymorphisms have been reported in prothrombin, fibrinogen, factor V, tissue factor, endothelial protein C receptor, and plasminogen activator inhibitor-1 genes. Some of them are associated with an increased risk of pulmonary emboli, acute myocardial infarction, stroke, and severe sepsis. Hence, the deletion polymorphism (4G) within the promoter region of the plasminogen activator inhibitor-1 gene leads to impaired fibrinolysis and influences the severity and outcome of meningococcal disease and the susceptibility to severe sepsis and multiple organ failure after trauma. The factor V Leiden mutation is associated with thrombotic events and has been reported to exacerbate purpura fulminans in meningococcal infection. Surprisingly, this genetic variant seems to provide a survival advantage in severe sepsis, underlying the extreme complexity of the interaction between inflammation and coagulation. The study of genetic polymorphisms might provide important insights into the pathogenesis of severe sepsis and could make it possible to identify individuals who are at risk of developing or dying of severe infections. As genetic associations are discovered, medical practice can become more preemptive, using the predictive ability of genetics to anticipate disease and recommend therapy.
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PMID:Importance of hemostatic gene polymorphisms for susceptibility to and outcome of severe sepsis. 1511 37

Despite the continuous description of new conditions pre-disposing for cerebral venous thrombosis (CVT), no apparent cause is found in about 30% of cases. Hyperhomocysteinemia (hyper-Hcy) is an established risk factor for deep venous thrombosis and stroke but has not been clearly associated with increased risk of CVT. We assessed the prevalence of hyper-Hcy and other thrombophilic risk factors in a population of 26 consecutive patients with non-pyogenic CVT, by review of a prospectively maintained database. The prevalences of hyper-Hcy and prothrombin G20210A, factor V G1691A and methylenetetrahydrofolate reductase (MTHFR) C677T mutations in these patients were compared with those in 100 healthy controls and 100 patients with cerebroarterial disease. The prevalence of hyper-Hcy was greater in patients with CVT (10/26, 38.5%) than healthy controls (13/100; OR 4.18, 95% CI 1.58-11.16) and comparable with that in patients with cerebroarterial disease (42/100). No significant differences were found in the prevalences of prothrombin or MTHFR mutation. No factor V mutation was found. Our findings indicate that hyper-Hcy is associated with an increased risk of CVT. Additional prospective cohort studies on large series of patients are required to clarify the time relationship between hyper-Hcy and the thrombotic event.
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PMID:Hyperhomocysteinemia and other thrombophilic risk factors in 26 patients with cerebral venous thrombosis. 1517 37

Fabry disease is associated with increased risk of premature stroke and presumptive ischemic cerebral lesions. In 57 consecutive patients, 35% of whom had lesions on brain MRI, the authors found that genotypes of polymorphisms G-174C of interleukin-6, G894T of endothelial nitric oxide synthase, factor V G1691A mutation, and the A-13G and G79A of protein Z were all significantly associated with cerebral lesions. These findings suggest that these proteins modulate Fabry cerebral vasculopathy.
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PMID:Effect of genetic modifiers on cerebral lesions in Fabry disease. 1660 44

Several studies indicate a high prevalence of factor V Leiden mutation as the most frequent coagulation defect found in patients with venous thrombosis. The relationship between this mutation and cerebrovascular disease has not been established in adults. In this investigation, we studied 29 patients with ischemic stroke and 20 with intracerebral hemorrhage, all of whom were compared with 20 controls. A region of the factor V gene containing the Leiden mutation site was amplified with polymerase chain reaction and the presence of mutation was determined with restriction enzyme digestion. We found no evidence of an association between factor V Leiden mutation and ischemic stroke or intracerebral hemorrhage. There was no evidence of association in subgroup the analysis by age, smoking status, myocardial infarction, hypertension, diabetes mellitus, or coronary disease. Factor V Leiden mutation doesn't seem to be associated with a risk of cerebrovascular disease.
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PMID:Factor V Leiden mutation in cerebrovascular disease. 1601 21

Although significant progress has been made in our understanding of sickle cell disease (SCD) and in the development of new therapies, many questions are still unanswered, and a cure remains elusive. This is particularly evident in the clinical heterogeneity of the disease. Studies have shown the importance of high hemoglobin F determinants and alpha-thalassemia as modifiers of disease severity, but these alone do not explain the diversity that is seen. This paper focuses on recent advances on the effect of nonglobin genetic modifiers on the SCD phenotype. The roles of polymorphic variants of (1) methylenetetrahydrofolate reductase gene in the pathogenesis of avascular necrosis, (2) factor V R485K and risk of venous thrombosis, and (3) UDP glucuronosyltransferase-1 polymorphism on serum bilirubin levels in SCD are discussed. Mention is made of genetic polymorphisms that might predispose to stroke. The application of gene expression profiling to the study of SCD is very promising and some preliminary data are provided.
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PMID:Sickle cell disease: a multigenic perspective of a single-gene disorder. 1610 9

Homocysteine is a sulfhydryl-containing amino acid formed during the metabolism of methionine. Rapidly accumulating evidence links elevated homocysteine levels to thrombosis via several mechanisms such as increased tissue factor expression, attenuated anticoagulant processes, enhanced platelet reactivity, increased thrombin generation, augmented factor V activity, impaired fibrinolytic potential, and vascular injury, including endothelial dysfunction. Molecular mechanisms underlying prothrombotic actions of homocysteine are incompletely understood and involve oxidative stress, DNA hypomethylation, and proinflammatory effects. Current evidence from retrospective and prospective studies supports the concept that higher total plasma homocysteine concentration is associated with increased risk of coronary artery disease, stroke, and venous thromboembolism. Hyperhomocysteinemia is currently considered a relatively weak prothrombotic factor. It is still unclear whether administration of vitamins, that reduce homocysteine levels acting as cofactors of the enzymes involved in the methionine metabolism, may decrease the risk of arterial and/or venous thromboembolic events. Ongoing clinical trials might help clarify this issue.
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PMID:Homocysteine and thrombosis: from basic science to clinical evidence. 1636 30

The prevalence rates of the platelet glycoprotein IIb/IIIa Leu33Pro allele (PLA2), and factor V G1691A Leiden mutation were determined in 109 appropriate for gestational age neonates with grade I intraventricular haemorrhage (IVH) and in 118 IVH-free control infants. The PLA2 allele frequency was 16.4 % in the group of full-term infants with grade I IVH, while it was 9.5 % in the relevant controls (p < 0.005); there was no difference in the PLA allele frequencies on comparing the IVH affected (8.34 %) and unaffected (9.2 %) premature infants. By contrast, the factor V Leiden allele frequency was increased only in the subgroup of premature infants with grade I IVH as compared with the appropriate premature controls (9.25 % vs. 3.34 %, respectively, p < 0.005). These data suggest that besides the factor V Leiden mutation, the PLA2 allele, which has already been suggested to have a role in neonatal alloimmune thrombocytopenia and certain subtypes of adult stroke, can have significance in the development of the events of IVH.
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PMID:Increased prevalence of glycoprotein IIb/IIIa Leu33Pro polymorphism in term infants with grade I intracranial haemorrhage. 1677 3

A thorough review of the literature and of personal files has allowed the gathering of 81 patients with rare congenital bleeding disorders and thrombotic phenomena. Sixteen of these patients had congenital afibrinogenemia, eight involved factor V deficiency, 20 factor VII defects, 33 factor XI deficiencies and only one, a factor XIII defect. Altogether 42 patients showed arterial thrombosis (myocardial infarction [MI] in 28 cases; ischemic stroke in 4; arterial occlusion in 8; 2 patients with disseminated intravascular coagulation (DIC)). Ages varied between 13 and 74. Twenty-two patients were males and 16 females. In four cases, sex was not reported. There were three fatalities: two after a MI and one because of heart failure. With regard to venous thrombosis: 9 patients had pulmonary embolism, 15 patients had deep vein thrombosis, 9 patients had both pulmonary embolism and deep vein thrombosis; 1 patient had superficial vein thrombosis, whereas, 5 cases had an unusual site venous thrombosis (two portal systems, two cerebral sinuses, one inferior vena cava) for a total of 39 cases. Age varied between 3 and 86. In this case, 20 patients were males and 17 were females. In two cases, sex was not reported. There were three fatalities: two because of pulmonary embolism and one because of inferior vena cava thrombosis. The fact that thrombosis has never been described in patients with factor II or factor X seems to underscore the central antithrombotic role that these two factors have in the coagulation system.
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PMID:Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. 1683 33

Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, beta-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.
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PMID:The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease. 1690 20

Stroke constitutes a major global challenge for health policy and healthcare economics. Reducing stroke burden requires extensive knowledge of risk factors and, if applicable, preventive control. Risk factors may be categorized in non-modifiable biological factors, such as age, gender, race/ethnicity; proatherosclerotic/prothrombotic factors (hypertension, diabetes, dyslipidaemia, other serologic and haemostasis factors); cardiac comorbidity (CAD, CHF, atrial fibrillation); lifestyle factors, which play an increasing role, e.g. smoking, physical inactivity, alcohol consumption. These traditional risk factors are extended by rapidly growing efforts in elucidating genetic backgrounds for stroke. Genetic polymorphisms of functionally or pathophysiologically important proteins are investigated in the setting of case-control-studies for their role as candidate genes. Meta-analyses have corroborated the association of the factor V-Leiden arg506gln, MTHFR-C677T, and ACE-insertion-deletion polymorphisms with stroke. Current population-based, genome-wide linkage analyses face high expectations for identifying new genetic risk factors.
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PMID:[Stroke: epidemiology, risk factors, and genetics]. 1714 42


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