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

Recently published American and British guidelines have comprehensively reviewed the indications for long term anticoagulation. The best evidence currently available supports the use of long term oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), venous thromboembolic disease, ischaemic heart disease, mural thrombi, and mechanical heart valves. Selected patients with valvular heart disease, cerebral vascular disease, and peripheral arterial disease may also benefit from the use of these drugs. When no specific contraindications are present, elderly patients with either paroxysmal or persistent NVAF should be considered candidates for treatment with anticoagulants. Pooled analyses of the results from 9 randomised trials demonstrate that warfarin significantly reduces the risk of ischaemic stroke in patients with NVAF, particularly those in a 'high risk' category defined by the presence of additional clinical or echocardiographic risk factors. Long term anticoagulation does not appear to be justified in patients with NVAF considered to be at 'low risk' for stroke. Because the prevalence of NVAF and most other cardiovascular conditions increases with advancing age, many elderly patients will be candidates for thromboprophylaxis. The potential benefit of long term anticoagulation must be carefully weighed against the risk of serious haemorrhage in such patients. Bleeding complications with anticoagulant drugs appear to occur more frequently in older patients than in younger individuals. Advanced age (>75 years), intensity of anticoagulation [International Normalised Ratio (INR) >4.0], history of cerebral vascular disease (recent or remote), and concomitant use of drugs that interfere with haemostasis [aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory drugs] are among the most important variables in determining an individual's risk for major bleeding with anticoagulants. Older patients often display increased sensitivity to the effects of warfarin, both in the early induction phase and during the long term maintenance phase of therapy. Conditions such as congestive heart failure, malignancy, malnutrition, diarrhoea and unsuspected vitamin K deficiency, enhance the prothrombin time response. The decision to interrupt anticoagulant therapy before elective surgery in elderly patients should evaluate the thrombotic risk of such a manoeuvre versus the risk of bleeding if anticoagulants are continued. In non-surgical patients, excessively elevated INRs without associated haemorrhage can usually be managed by simply witholding one or several doses of warfarin. If more rapid reversal is needed, small doses of phytomenadione (vitamin K1) can be administered safely without overcorrection or the development of vitamin K-induced warfarin resistance.
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PMID:Use of oral anticoagulants in older patients. 1093 7

The most common hereditary hypercoaguable states are factor V(Leiden) (FVL) and prothrombin mutations (PRO). FVL and PRO present with an incidence of approximately 5% in a heterogeneous population, and 45% to 63% of the thrombophilic population. The frequency of these mutations in the fetal population and their clinical importance is unknown. Fetal side thromboembolic events (FST) include congenital stroke and renal vein thromboses. In some cases, FST can be diagnosed by placental histopathology when avascular (infarcted) villi are present in a patent maternal vascular space. FST can present as placenta-fetal-vascular or fetal-visceral-vascular lesions. Causes include vascular damage from cord compression or inflammation, but most remain unclear. Potential causes of FST include FVL and PRO. We describe the incidence of FVL and PRO from a prospective group of 169 consecutive placentas and in a retrospective group of archived placentas diagnosed with placental FST. One each of FVL and PRO heterozygosity was found in the prospective set (< 1% incidence for each). Five prospective placentas were diagnosed with placental FST, for an incidence of 3%; all were wild-type for FLV and PRO. Twenty-seven of 65 archived FST cases had analyzable DNA to find 5 FVL heterozygotes (18.5%); all were wild-type for PRO. Twenty-one of 65 retrospective archived controls analyzable found 1 case of FVL heterozygosity (< 5%). We find that the frequency of FVL and PRO may be decreased in the pregnant population but increased in cases of placental FST. Because factor V Leiden heterozygosity carries an increased risk for thrombotic complications, we suggest placental diagnosis of fetal side thromboemboli warrants clinical evaluation for FVL in infant and potentially the parents.
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PMID:Frequency of factor V(Leiden) and prothrombin G20210A in placentas and their relationship with placental lesions. 1101 68

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

The effects of 4 weeks oral intake of Nigella sativa L. (NS) oil on some liver function tests and D-galactosamine- or carbon tetrachloride-induced hepatotoxicity were investigated in male albino rats. In another series of experiments, the effect of the oil on serum lipid profile was examined in male spontaneously hypertensive rats of stroke prone strain and Wistar Kyoto rats. The study showed that daily administration of the oil per se (800 mg/kg orally for 4 weeks) did not adversely effect the serum transaminases (ALT and AST), alkaline phosphatase, serum bilirubin or prothrombin activity in normal albino rats. When the oil was given for 4 weeks prior to induction of hepatotoxicity by D-galactosamine or carbon tetrachloride, it was able to give complete protection against d-galactosamine and partial protection against carbon tetrachloride hepatotoxicity. NS oil showed a favourable effect on the serum lipid pattern where the administration of the oil (800 mg/kg orally for 4 weeks) caused a significant decrease in serum total cholesterol, low density lipoprotein, triglycerides and a significant elevation of serum high density lipoprotein level.
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PMID:Nigella sativa L. oil protects against induced hepatotoxicity and improves serum lipid profile in rats. 1105 Jul 1

Hereditary thrombophilias are a heterogenous group of genetic coagulation disorders which, particularly in combination with acquired prothrombotic factors, induce a predisposition to thrombosis. After characterization of frequent thrombophilic syndromes like factor V-Leiden or the prothrombin 20210GA mutation, a number of case-control studies screened for the prevalence of these mutations in ischemic stroke and cerebral venous thrombosis (CVT). Our meta-analysis shows that factor V-Leiden and prothrombin are frequent and significantly associated with CVT (16.4% vs. 4.9% or 4.3, P < 0.001, and 12.1% vs. 1.9% or 5.8, P < 0.001). In ischemic stroke, only factor V-Leiden and not prothrombin is a weak but significant risk factor (5.9% vs. 2.6% or 1.6, P < 0.001, and 4.1% vs. 3.3% or 1.4, P = 0.1). The C677T homozygous point mutation in the MTHFR, a homocysteine-degrading enzyme, was also associated with arterial stroke (16% vs. 15% or 1.5, P < 0.001). For CVT, sufficient data are lacking. We therefore recommend screening for thrombophilia in CVT. In ischemic stroke, atrial premature complex (APC) resistance should be considered. As long as controlled studies are lacking, individual anticoagulant therapy must take hereditary and precipitating factors into account to assess potential thrombotic risk.
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PMID:[Hereditary thrombophilia with ischemiC stroke and sinus thrombosis. Diagnosis, therapy and meta-analysis]. 1113 89

Thrombophilia traditionally refers to rare inherited defects leading to enhanced coagulation, especially of the venous system. In recent years, a broader search for genetic polymorphisms of prothrombotic genes has been carried out to determine the relative impact on venous and arterial thrombosis. The bulk of evidence is drawn from numerous, often small, heterogeneous, case control association studies, with a variety of end points (deep venous thrombosis, myocardial infarction, or stroke). The data are often conflicting and inconclusive with only factor V Leiden and prothrombin polymorphisms having clear associations with venous thrombosis. Many of the polymorphisms interact with established cardiovascular risk factors, in particular smoking, to increase greatly the risk of a thrombotic episode. Future studies will need to consider the confounding factors of sample size, race, and clinical end points as well gene-environment interactions.
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PMID:Thrombophilia, polymorphisms, and vascular disease. 1119 48

Atrial fibrillation (AF) is a well-defined risk factor for ischemic stroke. Patients with lone AF represent a subgroup of AF patients with the lowest lifelong stroke risk. Nonvalvular atrial fibrillation (NVAF) confers a hypercoagulable state resulting in an increased risk of thromboembolism. This study was performed to determine the contributory role of alteration in the hemostatic markers of thrombin generation and fibrinolysis in patients with lone AF during acute ischemic stroke episode. We studied thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) concentrations in patients with acute middle cerebral artery ischemic stroke due to atherosclerotic large artery disease (n=50), lone AF (n=24) and cardioembolism (n=21). The values were compared with those of age-matched control subjects with lone AF and sinus rhythm (n=21 and 15, respectively). The mean F1+2 concentration was higher in the control subjects with lone AF in comparison with those without AF (p=0.014). Patients with stroke due to possible cardioembolism, from lone AF or other causes, had higher TAT (and marginally higher F1+2) concentrations than those with atherosclerotic stroke (p<0.001). tPA concentrations were not different among groups (p=0.89). PAI-I levels were marginally higher in stroke patients with lone AF and atherothrombotic large artery disease compared to the controls without AF (p=0.05). These results suggest that in the acute period of ischemic stroke secondary to lone AF, enhancement of the coagulatory activity occurs as a result of increased thrombin generation, similar to other possible sources of cardioembolism. Observed hemostatic alterations in acute ischemic stroke associated with lone AF may indicate some therapeutic and prognostic implications.
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PMID:Plasma levels of coagulation and fibrinolysis markers in acute ischemic stroke patients with lone atrial fibrillation. 1121 63

Our specific aim was to assess how thrombophilic exogenous estrogens interacted with heritable thrombophilias leading to non-arteritic ischemic optic neuropathy (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old patient and her immediate family. The proband had a 47 year history of 9 previous thrombotic episodes, and developed unilateral NAION 4 years after starting estrogen replacement therapy (ERT). The proband was heterozygous for two thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein IIIa P1A1/A2 polymorphism), and homozygous for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none had these 3 gene mutations together. The proband's mother and brother had deep venous thrombosis (DVT). The proband's brother, sister, nephew, daughter, and two granddaughters were homozygous for the C677T MTHFR mutation. The proband's brother was heterozygous for the G20210A prothrombin gene mutation. The proband's niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the platelet glycoprotein IIIa P1A1/A2 polymorphism. Of 238 normal controls, none had the niece's combination of 4 gene mutations. When ERT-mediated thrombophilia was superimposed on the proband's heritable thrombophilias, unilateral ischemic optic neuropathy developed, her tenth thrombotic event over a 5 decade period. When estrogen-progestin oral contraceptives were given to the proband's niece, she had an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia superimposed on heritable thrombophilia and hypofibrinolysis is associated with arterial and venous thrombi, and appears to be a preventable, and potentially reversible etiology for ischemic optic neuropathy and ischemic stroke.
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PMID:Interaction of heritable and estrogen-induced thrombophilia: possible etiologies for ischemic optic neuropathy and ischemic stroke. 1124 43

This paper aimed to investigate the effect of lumbrokinase on the anticoagulation and fibrinolysis in treating cerebral infarction. Lumbrokinase was used in patients with cerebral infarction. Patients were randomly divided into treatment group (n = 31) and control group (n = 20). Single blind method was used in this investigation. The Chinese stroke score was used to evaluate the results of treatment before and after administration of lumbrokinase. Kaolin partial thromboplastin time (KPTT), prothrombin time (PT), fibrinogen content, vWF content were analyzed, and tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI) activity, D-dimer level were assayed. In both groups, the stroke score decreased after administration, but in the treatment group, it was more obvious. In the treatment group, KPTT was prolonged, t-PA activity and D-dimer level increased, while the content of fibrinogen decreased significantly. There were no significant changes of PT and PAI activity in both groups. It is concluded that lumbrokinase is beneficial to the treatment of cerebral infarction. The effect of lumbrokinase is related to the inhibition of intrinsic coagulation pathway and the activation of fibrinolysis via an increase of t-PA activity.
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PMID:Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. 1132 42

Atrial fibrillation, the most common chronic arrhythmia, results in an increased risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be underused. The objective of this study was to examine the use of warfarin and prevalence of stroke in patients with rheumatic, nonrheumatic valvular and nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457 chronic atrial fibrillation patients with continuous follow-up in our hospital were identified as having rheumatic heart disease (n = 114): nonrheumatic valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used less often in patients with nonrheumatic valvular (16.7%) and nonvalvular diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001). In contrast, the prevalence of stroke among patients with nonvalvular disease was 40.3% which was similar to the 33.3% found in patients with rheumatic heart disease but significantly higher than the 24.6% found in patients with nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the trend of use of warfarin among the three groups of patients. Only 20.6% of patients on warfarin received monthly monitoring of prothrombin time. In conclusion, the anticoagulation therapy in our patients with chronic atrial fibrillation, regardless of their associated valvular diseases, is significantly underutilized. This underuse could account for a high prevalence of stroke. This risk of stroke, however, is less in patients with nonrheumatic valvular discase than in those with nonvalvular atrial fibrillation.
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PMID:Underutilization of anticoagulation therapy in chronic atrial fibrillation. 1132 7


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