Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence in the serum of antiphospholipid antibodies (aPL) is associated with venous and arterial thrombosis. This observation has led to the search for these antibodies in young patients with ischemic neurologic syndromes. However, 1% to 5% of healthy people may be found to have circulating aPL without necessarily being at increased risk of thromboembolism. Thus, the finding of APLA in a patient with cerebral ischemia does not necessarily provide an explanation for the etiology of the clinical syndrome. The aim of this study was to determine whether the presence of aPL in young patients with stroke or transient ischemic attacks represents a possible cause of hypercoagulability as defined by ongoing thrombin formation with resultant elevation of prothrombin fragment 1.2 (F1.2) levels. This was a retrospective, case-control study involving 57 subjects. Twenty-seven patients had a recent cerebrovascular ischemic event--either TIA or a stroke. Fifteen were positive for aPL, and 12 were aPL-negative. Thirty subjects, matched for age and sex with no history of cerebrovascular disease, served as controls. Of this group, 20 were aPL-positive and 10 were aPL-negative. Causes of hypercoagulability other than aPL were excluded by laboratory testing. A positive test for aPL was repeated after a 6-week interval and two positive tests were required for a patient to be regarded as being aPL-positive. Levels of F1.2 were measured by an ELISA technique. There was a significant difference (p < 0.05) in the mean F1.2 levels between the aPL-positive group with a history of cerebrovascular disease (mean F1.2 = 2.3733) and each of the other study groups. There was no statistically significant difference between any of the other study groups. Our findings suggest that F1.2 levels are elevated in young patients with cerebrovascular syndromes who have aPL and in whom other causes of hypercoagulability and atherosclerotic vascular disease are absent. Elevated F1.2 in these patients may be a potential marker of the hypercoagulable state associated with aPL.
 ...
PMID:Value of prothrombin fragment 1.2 (F 1.2) in the diagnosis of stroke in young patients with antiphospholipid antibodies. 1077 22

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.
 ...
PMID:Use of oral anticoagulants in older patients. 1093 7

The risk of venous thrombosis is increased in individuals who carry specific genetic abnormalities in blood coagulation proteins. Among Caucasians, the prothrombin G20210A and factor V Arg506Gln (FV R506Q) mutations are the most prevalent defects identified to date. We evaluated their influence on markers of coagulation activation among participants in the Second Northwick Park Heart Study, which recruited healthy men (aged 50-61 years) from nine general medical practices in England and Wales. They were free of clinical vascular disease and malignancy at the time of recruitment. Genotypes for the two mutations were analyzed using microplate array diagonal gel electrophoresis, and coagulation markers (factor XIIa; activation peptides of factor IX, factor X, and prothrombin; fibrinopeptide A) were measured by immunoassay. Factor VII coagulant activity and factor VIIa levels were determined by a functional clotting assay. Among 1548 men genotyped for both mutations, 28 (1.8%) and 52 (3.4%) were heterozygous for prothrombin G202 IOA and FV R506Q, respectively. The only coagulation marker that was significantly associated with the two mutations was prothrombin activation fragment FI+2 [mean +/- SD, 0.88 +/- 0.32 nmol/L in men with prothrombin G20210A (p = 0.002) and 0.89 +/- 0.30 in men with FV R506Q (p = 0.0001) versus 0.72 +/- 0.24 among non-carriers for either mutationl. This data provides conclusive evidence that heterozygosity for the prothrombin G20210A as well as the FV R506Q mutations in the general population leads to an increased rate of prothrombin activation in vivo.
 ...
PMID:Prothrombin activation is increased among asymptomatic carriers of the prothrombin G20210A and factor V Arg506Gln mutations. 1101 61

Dietary fat is known to influence the variables of blood coagulation and fibrinolysis associated with vascular disease. However, the role of fat content and/or fat composition of the diet in this regard is still not well understood. In the present study, we investigated the effects of three isoenergic diets of differing fat composition in nine healthy young men in a strictly controlled residential study. Subjects consumed the three experimental diets for periods of 2 weeks each, separated by a washout period of at least 5 weeks in a randomized crossover design. The diets provided 38% of total energy intake as fat, 45% as carbohydrate, and 17% as protein, and differed only with respect to the fatty acid composition (stearic acid-rich diet: 34.1% stearic acid, 36.6% oleic acid; oleic acid-rich diet: 65.8% oleic acid; linoleic acid-rich diet: 36.5% linoleic acid, 38% oleic acid). Blood samples were collected at the beginning and at the end of each dietary period from fasted subjects for determination of factor VII coagulant activity (FVIIc), activated factor VII (FVIIa), factor VII antigen (FVIIag), tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, fibrinogen, prothrombin fragment 1+2 (F(1+2)), and plasma lipids. There were no significant differences between diets in fasting plasma concentrations of FVIIc, FVIIa, FVIIag, fibrinogen, F(1+2), PAI-1 activity, and tPA activity. Plasma concentrations of lipids (high density lipoproteins, low density lipoproteins, triacylglycerols, and total cholesterol) were also unaffected. Although there were no changes in platelet aggregation response and membrane fluidity observed in any of the diets, increased anti-aggregatory prostaglandin E(1) binding to platelet membranes was observed only in the case of linoleic acid-rich diet. In conclusion, diets with very different fatty acid compositions, at 38% of energy as fat intake, did not significantly influence blood coagulation, fibrinolysis, or blood lipids in the fasting state in young healthy men.
 ...
PMID:A residential study comparing the effects of diets rich in stearic acid, oleic acid, and linoleic acid on fasting blood lipids, hemostatic variables and platelets in young healthy men. 1104 36

Fibrinogen plays a complex role in hemostasis, thrombosis, and vascular disease. Hyperfibrinogenemia is an independent vascular risk factor and dysfibrinogenemia can provoke thrombosis. Afibrinogenemia is usually responsible for hemorrhagic diathesis, and unexpected ischemic lesions are intriguing. We report the case of an afibrinogenemic patient, who at the age of 30 developed ischemic lesions of the feet related to severe stenosis of the iliac and hypogastric arteries. The biopsy of the iliac artery lesion showed an intense myointimal hyperplasia. We performed standard hemostatic analysis and analyzed the activation markers of platelets and coagulation factors and the kinetics of thrombin generation in the patient and in normal control plasmas treated or not with reptilase. Occlusive arterial lesions were attributed to a disruptive hematoma penetrating the vascular lumen. Thrombin concentration after calcium addition increase markedly in the afibrinogenemic patient and in defibrinated normal plasma, as compared to untreated normal plasma. Thrombin-antithrombin complexes (T-AT) were markedly enhanced while F1+2 prothrombin fragments stayed in the normal range. These results suggested activation of coagulation and in vivo circulating thrombin. Thrombin activates the platelets that secrete growth factors for smooth muscle cells and generate the intimal hyperplasia. Recurrent hemorrhage within the vessel wall might induce injury and local thrombin generation. Thrombin not trapped by the clot is available for platelet activation and smooth muscle cell migration and proliferation. The absence of a protective fibrin cap on the intima might account for intima vulnerability and embolization. Afibrinogenemia appears in this paradoxical situation as a vascular risk factor.
 ...
PMID:Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin. 1136 14

The factor V Leiden (FV Leiden) and prothrombin G20210A mutations, are the most common established genetic risk factors for deep vein thrombosis (DVT). However, the relationship between these mutations and arterial thrombotic syndromes (coronary heart disease, myocardial infarction, stroke) has not been established. Some studies have suggested a relationship between them, but other authors have considered it unlikely that these anomalies are a major risk factor for arterial thrombosis. From the clinical point of view, a question arises concerning the risk of repeated thrombosis in patients carrying one of these two mutations. The question is whether the recurrence is attributable to the mutations or to the presence of additional circumstantial risk factors. As the risk of repeated thrombosis varies considerably from one patient to another, decisions about long-term treatment require weighing the persistence of risk factors for vascular disease (venous and arterial), especially in selected cases such as young patients or patients with thrombosis of unusual localization.
 ...
PMID:Factor V Leiden and prothrombin G20210A in relation to arterial and/or vein rethrombosis: two cases. 1144 86

Plasma homocysteine has been associated with vascular disease and mortality. Experimental studies and studies on patients with vascular disease have indicated a thrombogenic potential of raised homocysteine levels. Studies on community samples are rare. We investigated the associations between homocysteine levels and selected coagulation factors in population-based random samples of 187 men from Pardubice (Czech Republic) and 147 men from Augsburg (Germany), aged 45 to 64 years. Czech men had higher mean levels of plasma homocysteine (10.3 vs. 8.9 micromol/l, P<.001) and of fibrinogen, von Willebrand factor (vWF), prothrombin fragment 1+2 (F 1+2) and D-Dimer (each P<.05). Plasma homocysteine was positively correlated with fibrinogen (r=.34) and vWF (r=.23, each P<.001) only in Czechs, and with D-Dimer in both Czechs and Germans (r=.26 and.21, respectively). Formal testing for interaction regarding the intercountry differences in the relationship with homocysteine revealed significance only for fibrinogen (P<.01). In multivariate analyses, the association of homocysteine with D-Dimer remained statistically significant after adjustment for indicators of chronic inflammation and fibrinogen. No significant correlation was found with Factor VII (F VII) activity or F 1+2. Homocysteine levels were also unrelated to traditional risk factors. In conclusion, in these cross-sectional studies we found moderate to strong associations between homocysteine and components of the endogenous hemostatic and fibrinolytic systems. The associations were slightly different between Czech and German men. These findings may help to better understand the role of homocysteine in atherothrombotic diseases.
 ...
PMID:Associations between homocysteine and coagulation factors--a cross-sectional study in two populations of central Europe. 1156 37

During thrombosis, vascular wall cells are exposed to clotting factors, including the procoagulant proteases thrombin and factor Xa (FXa), both known to induce cell signaling. FXa shows dose-dependent induction of intracellular Ca(2+) transients in vascular wall cells that is active-site-dependent, Gla-domain-independent, and enhanced by FXa assembly into the prothrombinase complex. FXa signaling is independent of prothrombin activation as shown by the lack of inhibition by argatroban, hirudin and the sulfated C-terminal peptide of hirudin (Hir(54-65)(SO3(-))). This peptide binds to both proexosite I in prothrombin and exosite I in thrombin. In contrast, signaling is completely blocked by the FXa inhibitor ZK-807834 (CI-1031). No inhibition is observed by peptides which block interaction of FXa with effector cell protease 1 receptor (EPR-1), indicating that this receptor does not mediate signaling in the cells assayed. Receptor desensitization studies with thrombin or peptide agonists (PAR-1 or PAR-2) and experiments with PAR-1-blocking antibodies indicate that signaling by FXa is mediated by both PAR-1 and PAR-2. Potential pathophysiological responses to FXa include increased cell proliferation, increased production of the proinflammatory cytokine IL-6 and increased production of prothrombotic tissue factor. These cellular responses, which may complicate vascular disease, are inhibited by ZK-807834.
 ...
PMID:FXa-induced responses in vascular wall cells are PAR-mediated and inhibited by ZK-807834. 1156 39

The acute spinal cord infarction is a rare cause of acute-onset paraplegia. Furthermore, it is specially uncommon that the infarction occurs in patients with apparent low predisposition to vascular disease. The 20210A allele of the prothrombin gene (causing a threefold-increased risk in venous thromboembolism) was recently associated with unexplained spinal cord infarction in young women under treatment with estrogens (contraceptive pill). We report a case of anterior spinal artery syndrome resulting from an ischaemic infarction at the anterior aspect of the spinal cord in a healthy 50-year-old woman, carrying this mutation, being the first published case under treatment with transdermal estradiol. She referred the typical sudden-onset back pain associated to clinical anterior spinal artery syndrome with sphincter dysfunction and nontraumatic paraplegia. A possible multiple sclerosis was ruled out and the steroids or immunoglobulin therapy induced no clinical improvement. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord infarction from T10 to T11, with increased signal in T2-weighted image (T2). Because she referred a previous thrombophlebitis and suffered a deep-vein thrombosis one month after paraplegia, a complete coagulation study was performed. Antithrombin, proteins C and S, homocysteine, factor V Leiden, lupus anticoagulant and anticardiolipin antibodies were all normal or negatives. In opposite, the 20210A variation was positive (heterozygous) and the factor VIIIc level was very high (280 U/dl eight months later). We argue the relative importance of both findings. The patient had no a substantial recovery over a period of 20 months.Certainly, the prothrombin 20210A seems to be associated with unexplained ischemic myelopathy among the young women with estrogens.
 ...
PMID:[Spinal cord infarction and recurrent venous thrombosis in association with estrogens and the 20210A allele of the prothrombin gene]. 1174 25

There is growing evidence for a role of factor XIII (FXIII) in vascular disease. FXIII measures were determined in (i) a nested case-control study from the Second Northwick Park Heart Study of 63 men with myocardial infarction (MI) and 124 age-matched controls and (ii) in a case-control study of 475 subjects with acute stroke and 461 controls followed up for 54 months for mortality. In both studies, measures of FXIII A- and B-subunit antigen, FXIII activity and prothrombin fragments (F1 + 2) were made. An in vitro model was used to investigate the effects of thrombin activity on FXIII A- and B-subunit antigen levels. In study 1, patients clinically free of coronary artery disease who later developed MI had lower adjusted FXIII A-subunit levels at recruitment (129.2%vs 113.3%, P = 0.007). In study 2, stroke patients with large vessel disease had lower A-subunit antigen levels (102.1%vs 127.2%, P < 0.001), but higher F1 + 2 levels (0.941%vs 0.753%, P < 0.05), than subjects with small vessel disease. Levels of FXIII A-subunit (100%vs 117%, P < 0.0001) were lower and F1 + 2 higher (1.020%vs 0.702%, P < 0.0001) in stroke patients who had died compared with those still alive at the end of the follow-up period. Low concentrations of FXIII A-subunit antigen predicted vascular outcome in otherwise healthy subjects and relate to both size of infarct and poor post-stroke survival in patients with acute ischaemic stroke. Low in vitro concentrations of FXIII A-subunit antigen wererelated to increased thrombin generation and, thus, increased risk of thrombotic events.
 ...
PMID:Factor XIII A-subunit concentration predicts outcome in stroke subjects and vascular outcome in healthy, middle-aged men. 1218 Oct 53


<< Previous 1 2 3 4 5 Next >>