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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitors in patients with hemophilia are a rare complication of a rare disease causing pain and disability in patients and impairment to the quality of their lives. Recent advances in treatment have brought improvements, but they have done so by absorbing larger amounts of financial resources. This study involved 52 Italian patients with hemophilia with high-responding inhibitors who were longitudinally observed for 18 months to evaluate concomitantly cost of care and quality of life. Overall, 0.6 bleeding episodes per patient per month were recorded. This frequency of events was lower than that reported in other cohorts of patients with hemophilia who were not taking inhibitors. The average monthly cost of care was, in euros, 18,000 (18,000 US dollars) per patient, mainly because of treatment products. Recombinant activated factor VII, mostly used for orthopedic surgery, represented 50% of the expenses. Quality of life, measured through validated questionnaires, was similar to that of patients with severe hemophilia without inhibitors. In particular, physical quality of life was similar to that in patients with diabetes and on dialysis, whereas mental quality of life was comparable to that in the general population. This study shows that hemophilia complicated by inhibitors, a prototype of rare disease, requires high amounts of resources for management that provides a satisfactory quality of life.
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PMID:Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group. 1281 59

Type 2 diabetes is characterised by insulin resistance in association with clustering of atherothrombotic risk factors (dysglycaemia, hyperinsulinaemia, hypertension, raised triglyceride, low HDL cholesterol and increased levels of plasminogen activator inhibitor-1 (PAI-1) and clotting factor VII). There is a 3-5 fold increase in risk of myocardial infarction rising to 10-20 fold in the presence of microalbuminuria and overall around 70-75% of subjects with type 2 diabetes die of cardiovascular disease. However, classical risk factors which associate with insulin resistance do not account for all the increased burden of vascular disease in diabetic subjects. Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow. Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein. In addition recent studies indicate that metformin has direct effects on fibrin structure/function and stabilises platelets, two important components of arterial thrombus. The United Kingdom Prospective Diabetes Study (UKPDS) reported that metformin was associated with a 32% reduction in any diabetes related endpoint (p<0.002), a 39% reduction in myocardial infarction (p<0.01) and a non-significant 29% fall in microvascular complications. The figures for macrovascular complications compare favourably for those described for other cardioprotective agents such as ACE inhibitors and statins. These findings confirm metformin as first line therapy in the management of obese insulin resistant type 2 diabetes and in the prevention of the vascular complications of this common condition.
Diabetes Metab 2003 Sep
PMID:Beneficial effects of metformin on haemostasis and vascular function in man. 1450

The role played by hemostasis in the pathogenesis of ischemic stroke is still controversial. In the present study, we looked for a possible association of ischemic stroke and high clotting activity of factor II (FII:C), factor V (FV:C), factor VII (FVII:C), factor X (FX:C) and fibrinogen. We investigated 157 non-anti-coagulated patients (86 males, 71 females; median age 41 y, range 16-73 ), who had survived ischemic stroke for at least 2 months, and 193 healthy controls with similar age and sex distribution (104 males, 89 females; median age 39 y, range 19-74). Patients showed significantly higher body mass index, as well as significantly higher prevalence of arterial hypertension, smoking and hyperlipidemia. FV:C (p = 0.05), FX:C (p = 0.04) and fibrinogen (p = 0.05) were higher in patients as compared to controls. In a univariate risk analysis FX:C and FV:C were associated with the relative risk for ischemic stroke showing an odds ratio (OR) of up to 2.8 (95% CI: 1.05-7.6) and 3.4 (95%CI: 1.4-7.9), respectively, for levels above 130%. In a multivariate analysis using a logistic regression model including age, sex, arterial hypertension, smoking habit, diabetes, hyperlipidemia, BMI and the coagulation factors, FV:C was still found to significantly (p=0.03) add to the risk of ischemic stroke. An increase of factor FV:C by 10% was associated with an increase in the relative risk of 19% (95% CI.: 2%-38%). In conclusion, we found a high plasma level of FV:C to be a prevalent (FV:C > 130% in 20/157 patients) and independent risk factor for ischemic stroke.
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PMID:Hemostatic risk factors in ischemic stroke. 1465 42

Candidate gene polymorphisms related to inflammation, thrombosis and lipid metabolism have been implicated in the development of ischemic stroke. Using DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we genotyped 92 polymorphisms from 56 candidate genes among 319 individuals who subsequently developed ischemic stroke and among 2092 individuals who remained free of reported cardiovascular disease over a mean follow-up period of 13.2 years to prospectively determine whether candidate gene polymorphisms contribute to stroke risk. After adjustment for multiple comparisons and age, smoking, body mass index, hypertension, hyperlipidemia and diabetes, two related to inflammation [a val640leu polymorphism in the P-selectin gene (OR=1.63, 95% CI 1.22-2.17, P=0.001) and a C582T polymorphism in the interleukin-4 gene (OR=1.40, 95% CI 1.13-1.73, P=0.003)] were found to be independent predictors of thrombo-embolic stroke. In bootstrap replications, the inclusion of genetic information from these two polymorphisms improved prediction models for stroke based upon traditional risk factors alone (ROC 0.67 versus 0.64). Two polymorphisms related to thrombosis (an arg353gln polymorphism in the factor VII gene and a T11053G polymorphism in the plasminogen activator inhibitor type-1 gene) and one related to lipid metabolism [a C(-482)T polymorphism in the apolipoprotein CIII gene] achieved nominal significance, but were not found to be independent predictors after multiple comparison adjustment. Two inflammatory candidate gene polymorphisms were identified which were independently associated with incident stroke. These population-based data demonstrate the ability of prospective, epidemiological studies to test candidate gene associations for athero-thrombotic disease.
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PMID:Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. 1468 4

Neonatal thrombosis is a serious event that can cause mortality or result in severe morbidity and disability. The most important risk factor for the development of thrombosis during the neonatal period is the presence of an indwelling central line and consequently the vessels involved tend to be those most frequently used for catheterization. Other documented risk factors for the development of neonatal thrombosis include asphyxia, septicemia, dehydration, maternal diabetes and cardiac disease. Main laboratory findings for the diagnosis of hypercoagulable states, include shortened aPTT, decreased levels of inhibitors (AT III, Protein C and Protein S), increased resistance to activated protein C, defective fibrinolysis (basal and after stimuli), increased levels of clotting factors (fibrinogen, factor VII, factor VIII, etc.), increased and/or hyperactive platelets, increased whole blood and/or plasma viscosity, Antiphospholipid antibodies and presence of prothrombotic molecular defects like FV Leiden, P20210 and MTHFR. Approximately 4% and 2% respectively of Caucasians are heterozygous for these gene defects. Their causative role in neonatal thrombosis is unknown but they may have a contributory role in the pathogenesis of thrombosis in neonates.
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PMID:Neonatal thrombosis. 1470 31

Periodontal disease is a chronic infection of the gums characterized by a loss of attachment between the tooth and bone, and by bone loss. We evaluated cross-sectionally the association between periodontal disease and C-reactive protein (CRP), fibrinogen, factor VII, tissue plasminogen activator (t-PA), LDL-C, von Willebrand factor, and soluble tumor necrosis factor receptors 1 and 2. The final sample consisted of 468 men (ages 47-80 yrs), participating in the Health Professional Follow-up Study, who provided blood and were free of CVD, diabetes, and cancer. In multivariate regression models controlling for age, cigarette smoking, alcohol intake, physical activity, and aspirin intake, self-reported periodontal disease was associated with significantly higher levels of CRP (30% higher among periodontal cases compared with non-cases), t-PA (11% higher), and LDL-C (11% higher). Based on our data, periodontal disease showed significant associations with biomarkers of endothelial dysfunction and dyslipidemia, which may potentially mediate the association between periodontal and cardiovascular disease.
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PMID:Periodontal disease and biomarkers related to cardiovascular disease. 1474 54

Activation of the coagulation cascade contributes to early graft loss and intraportal thrombotic events in clinical islet transplantation. Although these complications were shown to be related to the presence of tissue factor in human islet preparations, the contribution of duct cells, which represent a major contaminant of clinical islet isolates, has not been specified so far. Herein, we used flow cytometry, immunohistochemistry, RT-PCR, and functional coagulation assays to demonstrate that duct cells exert a potent factor VII-dependent procoagulant activity related to their expression of tissue factor. Both the classical membrane-bound and the recently described soluble form of tissue factor were shown to be synthesized by duct cells. We conclude that contaminating duct cells contribute to early beta-cell damage after islet transplantation through their involvement in tissue factor-mediated thrombotic and inflammatory events.
Diabetes 2004 Jun
PMID:Human pancreatic duct cells exert tissue factor-dependent procoagulant activity: relevance to islet transplantation. 1516 41

Simvastatin, a widely used 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, effectively reduced cardiac death and ischemic events in patients with coronary heart disease (CHD) and diabetes mellitus (DM). The mechanism of cardiovascular benefits of statins in DM remains unclear. We examined how simvastatin influences the levels of several in vivo markers for coagulation and fibrinolysis in 26 Type 2 DM patients. The diabetic patients received 20 mg/day of simvastatin up to 12 months. The levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and triglycerides in peripheral circulation of patients were significantly reduced after > or =6 weeks of simvastatin treatment. Levels of prothrombin fragment 1+2 (F1+2), factor VII, plasminogen activator inhibitor-1 (PAI-1) and tissue factor pathway inhibitor (TFPI) antigens, but not tissue plasminogen activator (tPA) antigen, in the pre-simvastatin plasmas of the diabetic patients were significantly higher than the levels found in plasmas of healthy subjects. Significant reductions in F1+2 and PAI-1 levels were evident > or =6 weeks after the diabetic patients received simvastatin. Levels of total tPA, TFPI, FVII, hemoglobin A1c, fasting blood glucose, and insulin in the diabetic patients' plasma were not significantly altered by simvastatin treatment. Positive correlations were found between PAI-1 versus TC, PAI-1 versus LDL-c, and FVII versus triglycerides in the plasmas of simvastatin-treated patients. The results suggest that simvastatin reduces in vivo prothrombinase activity and PAI-1 levels in type 2 DM patients. These actions may contribute to the protective properties of simvastatin against ischemic events in diabetic patients.
Diabetes Res Clin Pract 2005 Nov
PMID:Impact of simvastatin on hemostatic and fibrinolytic regulators in Type 2 diabetes mellitus. 1618 73

Advanced glycation endproducts (AGEs) form at an accelerated rate in diabetes and contribute to the development of macrovascular disease. Their precursors are detoxified by the glyoxalase system. Perturbations of the glyoxalase-1 gene may alter AGEs' interactions and affect pro-thrombotic factors. We screened the glyoxalase-1 gene for mutations and measured pro-thrombotic markers in 537 subjects from 89 healthy probands. Common single nucleotide polymorphisms (SNPs) were identified at positions -7 (C to T) and 20203 (C to A) from the translation start site. These SNPs were in Hardy-Weinberg equilibrium (CC=105, CA=266, AA=148; p>0.05; CC=126, CT=279, TT=114; p>0.05, respectively) and in linkage disequilibrium (D=27%, p<0.01), with mutant allele frequencies of 48% and 52% respectively. A significant association was found between SNPs at position 20203 and PAI-1 antigen concentrations and -7 and factor XIII A2B2 complex (p=0.001 and p=0.042). After Bonferroni correction a significant association remained between the SNP at 20203 and PAI-1 concentrations (p=0.005), and after adjustment for pedigree the association accounted for 1.3% of its heritability (p=0.04). No significant associations were found for SNP -7 T to C and factor VII activity, tPa concentrations, fibrinogen concentrations or factor XIII concentrations and SNP 20203 C to A and factor VII concentrations, PAI-1 concentrations, tPa concentrations or fibrinogen concentrations. Common variants in the glyoxalase-1 gene are associated with some pro-thrombotic factors, account for part of their heritability in healthy pedigrees and may alter susceptibility to macrovascular complications.
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PMID:Common polymorphisms in the glyoxalase-1 gene and their association with pro-thrombotic factors. 1630 54

Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor.
Diabetes 2006 Jan
PMID:Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. 1638 Apr 94


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