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

Hemostasis factors may influence the pathophysiology of stroke. The role of brain hemostasis in ischemic hypertensive brain injury is not known. We studied ischemic injury in spontaneously hypertensive rats in relation to cerebrovascular fibrin deposition and activity of different hemostasis factors in brain microcirculation. In spontaneously hypertensive rats subjected to transient middle cerebral artery occlusion versus normotensive Wistar-Kyoto (W-K) rats, infarct and edema volumes were increased by 6.1-fold (P < 0.001) and 5.8-fold (P < 0.001), respectively, the cerebral blood flow (CBF) reduced during middle cerebral artery occlusion (MCAO) by 55% (P < 0.01), motor neurologic score increased by 6.9-fold (P < 0.01), and cerebrovascular fibrin deposition increased by 6.8-fold (P < 0.01). Under basal conditions, brain capillary protein C activation and tissue plasminogen activator activity were reduced in spontaneously hypertensive rats compared with Wistar-Kyoto rats by 11.8-fold (P < 0.001) and 5.1-fold (P < 0.001), respectively, and the plasminogen activator inhibitor-1 antigen and tissue factor activity were increased by 154-fold (P < 0.00001) and 74% (P < 0.01), respectively. We suggest that hypertension reduces antithrombotic mechanisms in brain microcirculation, which may enhance cerebrovascular fibrin deposition and microvascular obstructions during transient focal cerebral ischemia, which results in greater neuronal injury.
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PMID:Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model. 1089 83

Although first-time miscarriages are usually caused by chromosomal defects, about 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels. Of recurrent miscarriages, about 7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to anatomical defects. Recurrent miscarriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, prescreened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evaluation. A total of 160 of these have been analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened women). The mean age was 33 years; the mean number of miscarriages before referral was three. All women with a procoagulant defect (149) were treated with preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every 12 hours was added immediately postconception; both agents were used to term delivery. Only two of 149 patients failed therapy. The defects found were as follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%; protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had more than one defect. In the group with antiphospholipid syndrome, 24% only had a subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin antibody or lupus anticoagulant. This finding is similar to that recently reported in early age ischemic stroke patients (<50 years old). In summary, about 55% of patients with recurrent miscarriage harbor a procoagulant defect to account for placental vascular occlusion. More than 98% will have a normal term delivery with preconception aspirin (ASA) and addition of postconception heparin to term. Patients should be screened by an obstetrician or by reproductive specialists for hormonal and anatomic defects before initiating a procoagulant evaluation; if such prescreening is done, the yield of a defect is high and appropriate therapy leads to an excellent outcome.
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PMID:Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group. 1089 70

Inherited gene defects related to the coagulation system have been reported as risk factors for stroke. Recently, a genetic component in the factor V (FV) gene that contributes to activated protein C resistance both in the presence and absence of FV 1691 G-->A was reported. This highly conserved FV gene haplotype was marked as R2 polymorphism, an A to G alteration at position 4070 in exon 13 that predicts the His 1299 Arg substitutions. The aim of this study was to evaluate the role of this mutation in Turkish children with ischemic infarct. The case-control study included 48 patients with cerebral infarction; all were 18 years of age or younger (range: 10 months to 18 years). Ten (20.8%) of the 48 patients were found to carry the FV 1299 His-->Arg mutation, one being homozygous. One patient who had a combination of FV 1691 G-->A and protein C deficiency also carried the FV 4070A mutation. A homozygous FV 1299A patient had a prothrombin (PT) 20210A mutation in the heterozygous state. The cerebral infarct risk for FV 1299 was found to be 2.4 (95% confidence interval 0.9-6.8) for all groups. When underlying conditions were excluded, the incidence of FV 1299 was found to be 8/35 (22.8%), but the risk was almost the same. When two other common thrombophilic mutations (i.e. FV 1691 G-->A and PT 20210 G-->A) were excluded, the incidence of FV 4070 mutation increased to 7/21 (33.3%). The risk also increased to 3.9 (95% confidence interval 1.2-12.3).
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PMID:Factor V (His 1299 Arg) in young Turkish patients with cerebral infarct. 1101 61

We report a case of stroke in a child with acquired protein C deficiency receiving valproic acid (VPA). To investigate the possible association of VPA with protein C deficiency, protein C levels were measured in 20 children receiving VPA monotherapy and 20 children receiving other anticonvulsants. Protein C levels were reduced in up to 45% of the VPA-treated subjects.
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PMID:Protein C deficiency related to valproic acid therapy: a possible association with childhood stroke. 1106 May 40

Childhood ischemic stroke, including arterial ischemic stroke (AIS) and sinovenous thrombosis (SVT), is relatively rare in children but can result in devastating morbidity and mortality. An understanding of the etiology of childhood stroke is important because strategies for primary and secondary prevention can be devised. Prothrombotic disorders may contribute to the etiology of childhood stroke, and include deficiencies of antithrombin, protein C, protein S, plasminogen, and presence of Factor V Leiden, Prothrombin gene G20210A, dysfibrinogenemia, antiphospholipid antibodies, hyperhomocysteinemia, and elevated lipoprotein (a). The overall incidence of prothrombotic disorders in childhood AIS is estimated to be 20% to 50% in most studies and, in childhood SVT, to be 33% to 99%. In addition, hyperlipidemia, polycythemia, iron deficiency anemia, and platelet disorders may result in a prothrombotic state associated with ischemic stroke. The etiologic contribution of these prothrombotic disorders to initial and recurrent stroke has not been clearly defined; however, additional risk factors are usually present in affected children. Given the prevalence of prothrombotic disorders in childhood stroke, and their likely causative role, children with stroke should be screened for prothrombotic disorders. Future prospective and multicenter studies will elucidate the contribution of specific prothrombotic disorders to initial and recurrent stroke, and optimal therapy.
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PMID:Prothrombotic disorders and ischemic stroke in children. 1120 19

Thrombomodulin is an important endothelial anticoagulant protein that decreases thrombin activity and activates protein C. Our recent study has shown that the G-33A promoter mutation of thrombomodulin gene is associated with coronary artery disease. This study was conducted to determine whether the G-33A mutation in the promoter region of thrombomodulin gene is a genetic risk factor for ischemic stroke or carotid atherosclerosis. The functional significance of this mutation was also evaluated. We recruited 333 patients (mean age 64 years, 59% male) with ischemic stroke and 257 age- and sex-matched controls. In all study participants, carotid atherosclerosis was assessed by Duplex scanning, and thrombomodulin G-33A promoter mutation was detected by single-strand conformation polymorphism. Luciferase reporter gene assay was used to assess the influence of this mutation on thrombomodulin promoter activity. There was no significant difference in the thrombomodulin G-33A mutation frequency (GA+AA genotypes) between the stroke and the control groups (18.3 vs. 24. 1%, P=0.105). The G-33A mutation frequency was also similar between the study participants with and without carotid atherosclerosis (22.2 vs. 19.8%, P=0.550). When only younger subjects (age </=60 years) were included in the analysis, however, we found the mutation occurred more frequently in participants with carotid atherosclerosis (33.3 vs. 17.3%, odds ratio [OR]=2.38, 95% confidence interval [CI]=1.16-4.90, P=0.027). Multiple logistic regression analyses showed that only diabetes mellitus (OR=3.11, 95% CI=1.33-7.30, P=0.009) and G-33A mutation (OR=2.46, 95% CI=1.14-5.29, P=0.021) were associated independently with carotid atherosclerosis in younger subjects. As assessed by luciferase reporter gene assays, the contructs bearing the G-33A mutation showed a significant decrease (36+/-12%) in transcriptional activity in comparison with the wild type constructs. Our findings suggest that G-33A mutation reduces the thrombomodulin promoter activity and is associated with carotid atherosclerosis in younger subjects.
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PMID:Functional mutation in the promoter region of thrombomodulin gene in relation to carotid atherosclerosis. 1220 14

Effective and safe methods of preventing venous thromboembolism (VTE) are now widely available, but a significant proportion of patients develop VTE either because thromboprophylaxis has not been used or because the intensity of thromboprophylaxis is not matched to the level of risk. Thromboembolic risk varies widely according to the clinical setting and presence of underlying risk factors, but VTE may not be suspected even in high-risk patients. Clinical risk factors for VTE include recent surgery, cancer, stroke, previous VTE, immobilization, and advanced age. Recent attention has focused on the role of inherited and acquired molecular factors in determining overall thromboembolic risk. These factors include the classic thrombophilias-deficiencies of antithrombin III, protein C, and protein S-and several newly described molecular risk factors: factor V Leiden, the prothrombin 20210A gene mutation, and hyperhomocysteinemia. Based on emerging knowledge of risk factors, several risk assessment models (RAMs) have been devised that stratify patients according to overall VTE risk, allowing thromboprophylaxis to be tailored appropriately. Compared with older risk assessment formulas, current RAMs are simpler and include specific recommendations for thromboprophylaxis based on the available scientific evidence. Consensus documents on VTE prevention classify patients into low-, moderate-, and high-risk categories. More recently, a new risk group, very high risk, has been described. Very-high-risk patients are especially prone to thromboembolic complications and need intensive and in some cases prolonged thromboprophylaxis.
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PMID:Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease. 1144 39

Congenital protein C deficiency is now widely recognized as a genetic risk for venous thrombosis. However, it remains uncertain whether this condition also confers risk for arterial thrombosis. We evaluated the association of congenital protein C deficiency with hypertension and silent cerebrovascular disease using brain magnetic resonance imaging (MRI) (T1- and T2-weighted and proton density images) in a large family pedigree of protein C deficiency diagnosed by gene analysis, compared with 46 non-pedigree related control subjects with normal protein C levels (> or = 75%) who were selected from among 55 asymptomatic hypertensive subjects matched for age and cardiovascular risk factors. Of the 58 living subjects in this pedigree, we measured plasma protein C levels in 45 subjects, and found 2 cerebral infarctions in the 24 heterozygotic subjects, whereas there was no stroke in the 21 normal homozygotic subjects. We performed brain MRI in 14 asymptomatic hypertensive subjects without any cardiovascular disease and in two patients with cerebral infarction, and found 28 cerebral infarcts (two corresponded to the patients' neurologic deficits and 26 were silent). All were lacunar infarcts < 10 cm in size. A total of 25 silent lacunar infarcts were found in nine heterozygotic subjects, whereas only one was found in the seven normal homozygotic subjects (2.8 v 0.14 lacunes per person, P = .002). No advanced white matter hyperintense lesions in T2-weighted images were found in either group. The prevalence of silent lacunar infarcts in the heterozygotic subjects was also significantly higher than that in normal control subjects (1.0 per person, P = .01). Concerning the distribution of silent infarcts, the number of lacunes located in the basal ganglia was higher in the heterozygotic subjects (2.3 per person, P < .001) than in the seven normal homozygotic subjects (0.14 per person) or in the control group (0.28 per person), whereas the number of lacunes in the white matter was not different among the groups. In conclusion, congenital protein C deficiency may accelerate the progression of silent cerebral infarct formation in hypertension, particularly in the basal ganglia, and may be a potential risk for stroke or vascularly induced dementia.
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PMID:Silent cerebral infarcts in basal ganglia are advanced in congenital protein C-deficient heterozygotes with hypertension. 1149

A subgroup of children with arterial ischemic stroke in the pre- or perinatal period present with delayed diagnosis. We identified 22 children who met the following criteria: (1) normal neonatal neurological history, (2) hemiparesis and/or seizures first recognized after two months of age, and (3) computed tomography or magnetic resonance imaging showing remote cerebral infarct. Laboratory evaluations included protein C, protein S, antithrombin, activated protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin antibody (ACLA), and lupus anticoagulant. Not all children received all tests. Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve were boys. Fourteen had left hemisphere infarcts. Median age at presentation was 6 months. Eighteen had gestational complications. Fourteen children had at least transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with FVL + MTHFR = 1); six of these children had family histories suggestive of thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes included persistent hemiparesis in 22; speech, behavior, or learning problems in 12; and persistent seizures in five, with no evidence of further stroke in any patient. The persistence and importance of coagulation abnormalities in this group need further study.
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PMID:Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. 1150 98

Authors discussed the known risk factors of venous thromboembolism (VTE), which is complex disease with two manifestations: deep venous thrombosis (DVT) and pulmonary embolism (PE). Acquired risk factors of VTE are following: age over 40 years, bed rest, surgery, trauma, cancer, myocardial infarction, ischemic stroke, use of oral contraceptives, hormone-replacement therapy, pregnancy and puerperium, previous VTE, long lasting travel and presence of antiphospholipid antibodies. Group of genetic defects predisposing to thromboembolic events are called thrombophilia. The best known causes of thrombophilia are: resistance to activated protein C (factor V Leiden), the prothrombin 20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and abnormality in the fibrinolytic system. Genetic predisposition to thrombosis may be detected in up to one-third of patients with VTER and more than 50% of patients with familial thrombosis. Detection of factor V Leiden is important for patients: with recurrent incidences of VTE, with other known causes of thrombophilia and in members of families with frequent occurrence of VTE. It is important also to detect deficiency of: protein C, protein S and especially of antithrombin in patient with previous VTE, because such patients have 8 to 10 fold increase risk of next incident of VTE. Chronic prevention of thrombosis should be used in all these cases.
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PMID:[Risk factors of venous thromboembolism]. 1155 14


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