thromboplastin and Hyperlipidemias

Hyperlipidemia affects millions of people worldwide and is a major risk factor for cardiovascular disease. People with hyperlipidemia have elevated levels of serum cholesterol and an increased risk of thrombosis. Studies have suggested that oxidized lipoproteins, such as oxidized low-density lipoprotein (oxLDL), contribute to the development of a pro-thrombotic state. In this review, we discuss our recent studies demonstrating a role for hematopoietic cell-derived tissue factor (TF) expression in the activation of coagulation and increased thrombosis associated with hyperlipidemia. In addition, we investigated the effect of simvastatin on TF expression and coagulation. We found that simvastatin reduced leukocyte TF expression, TF⁺ microparticles, and coagulation. These results and earlier studies suggest that the anti-coagulant activity of statins is due, in part, to their ability to reduce monocyte TF expression in patients with cardiovascular disease.

Topics: Animals; Blood Coagulation; Disease Models, Animal; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Simvastatin; Thromboplastin; Thrombosis

Topics: Adult; Aged; Animals; Cardiovascular Diseases; Cerebrovascular Disorders; Cohort Studies; Cross-Sectional Studies; Epidemiologic Methods; Europe; Factor VII; Female; Fibrinogen; Hemostasis; Humans; Hyperlipidemias; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Risk Factors; Thromboplastin; Triglycerides; United States

After a simplified survey of the chemistry of phospholipids (PL) their presence in the lipid part of thromboplastin is dealt with, the significance of this structure being stressed. In addition, the condition, mode of action and synthesis of PL in blood platelets are extensively discussed and the impact of the composition of thrombocytic PL in the membrane and granular fraction by plasma lipid substances is referred to. The relations between single forms of PL and those proteins activating coagulation are represented and the conditions for the development of such activating complexes are referred to. Subsequently the coagulation stimulating properties of PL, thromboplastin, thrombocytes, and artifically produced PL are compared and the attempt is made to draw certain conclusions from sometimes contradictory results. Finally, the anticoagulative effect of phosphatidylserin is referred to.

Topics: Animals; Blood Coagulation; Blood Platelets; Cattle; Cell Membrane; Factor VII; Humans; Hyperlipidemias; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylserines; Phospholipids; Plant Extracts; Platelet Factor 3; Rats; Thromboplastin; Type C Phospholipases

Topics: Animals; Arteries; Arteriosclerosis; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Endothelium; Fatty Acids; Fatty Acids, Nonesterified; Humans; Hyperlipidemias; Lipids; Phospholipids; Platelet Adhesiveness; Platelet Aggregation; Prostaglandins; Thromboplastin; Thrombosis

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Butter; Chromatography, Thin Layer; Contraceptives, Oral, Synthetic; Dietary Fats; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Male; Oils; Phosphatidylethanolamines; Phosphatidylinositols; Phosphatidylserines; Pregnancy; Rabbits; Rats; Thromboplastin; Thrombosis; Time Factors; Wounds and Injuries; Zea mays

The effects of statins on platelet activation markers, chemokines and adiponectin, were investigated in 135 patients with hyperlipidemia. Of the 135 hyperlipidemic patients, 63 were allocated to the simvastatin group, treated with simvastatin at the dose of 10 mg daily, and the remaining 72 were allocated to the pitavastatin group, treated with pitavastatin at the dose of 2 mg daily. Plasma levels of platelet-derived microparticles (PDMP), cell adhesion molecules (sCD40L and sP-selectin), chemokines [monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normally T-cell expressed and secreted] and adiponectin were measured at the baseline and after 6 months of treatment in both the groups. In addition, we carried out a basic study to investigate the MCP-1-dependent induction of tissue factor expression on a histiocytic cell line (U937 cells). The plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 were higher, whereas those of adiponectin were lower, in the hyperlipidemic patients than in the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, whereas plasma adiponectin was negatively correlated, with the plasma levels of MCP-1. No significant differences in the plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 measured before and after treatment were observed in either the simvastatin or pitavastatin group. A significant increase of the plasma adiponectin levels was observed after 6 months of treatment with pitavastatin but not after an equal duration of treatment with simvastatin. When pitavastatin-treated patients were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases of the plasma MCP-1, PDMP and sCD40L levels were observed after pitavastatin treatment in the responder group. In the aforementioned basic study, MCP-1 by itself did not induce the expression of tissue factor on the U937 cells. However, the recombinant sCD40L-induced expression of tissue factor on U937 was enhanced by the addition of MCP-1. These findings suggest that PDMP, sCD40L and MCP-1 may participate in the development of atherothrombosis in patients with hyperlipidemia and that pitavastatin may exert an adiponectin-dependent antiatherothrombotic effect in hyperlipidemic patients.

Topics: Adiponectin; Adult; Aged; Atherosclerosis; CD40 Ligand; Cell-Derived Microparticles; Chemokine CCL2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male; Middle Aged; P-Selectin; Quinolines; T-Lymphocytes; Thrombophilia; Thromboplastin; U937 Cells

Hyperlipidaemia is a causal factor in the ethiopathogenesis of atherosclerosis. Statins are the cornerstone drug therapy for LDL-cholesterol (LDL-c) lowering, that exert beneficial effects beyond lipid lowering. Circulating microparticles (cMPs), microvesicles released by activated cells into the bloodstream, are markers of vascular and inflammatory cell activation with tentative role in disease progression. However, the role of statins on cMPs seems controversial. We aimed at the evaluation of the effects of lipid-lowering treatment (LLT) on cMP generation in patients in primary prevention of atherosclerosis. A case-control study was conducted in hypercholesterolaemic patients receiving LLT with statins and normocholesterolaemic controls (LLT+ and LLT-, respectively, n=37/group), matched by age, gender and LDL-c levels. cMPs were characterised by flow cytometry using annexin-V and cell-specific antibodies. In LLT+-patients overall numbers of cMPs (p<0.005) were lower than in controls. Levels of cMPs carrying parental cell markers from vascular and circulating cell origin (platelet, endothelial cell, pan-leukocyte and specific-leukocyte subsets) were significantly lower in blood of LLT+ compared to LLT--patients. Moreover, MPs from LLT+-patients had reduced markers of activated platelets (αIIbβ3-integrin), activated inflammatory cells (αM-integrin) and tissue factor. The effect of LLT on cMP shedding was found to be accumulative in years. cMP shedding associated to cardiovascular risk in LLT+-patients. In summary, at similar plasma cholesterol levels patients on statin treatment had a significant lower number of cMPs carrying markers of activated cells. These findings indicate that statins protect against vascular cell activation.

Topics: Adult; Annexin A5; Atherosclerosis; Blood Platelets; Case-Control Studies; Cell-Derived Microparticles; Cholesterol, LDL; Endothelial Cells; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Inflammation; Leukocytes; Male; Middle Aged; Primary Prevention; Thromboplastin

High plasma levels of C-reactive protein (CRP) constitute a powerful predictive marker of cardiovascular events. Several lines of evidence suggest that CRP has prothrombogenic effects. However, whether CRP directly participates in the pathogenesis of thrombosis in vivo has not been fully clarified.. To test whether human CRP (hCRP) affects arterial thrombus formation after balloon injury of smooth muscle cell (SMC)-rich or macrophage-rich neointima.. We compared the susceptibility of transgenic (Tg) rabbits expressing hCRP (46.21 ± 13.85 mg L(-1), n = 22) and non-Tg rabbits to arterial thrombus formation after balloon injury of SMC-rich or macrophage-rich neointima.. Thrombus size on SMC-rich or macrophage-rich neointima was significantly increased, and was accompanied by an increase in fibrin content in hCRP-Tg rabbits, as compared with non-Tg rabbits. Thrombus size did not significantly differ between SMC-rich and macrophage-rich neointima in hCRP-Tg rabbits. Tissue factor (TF) mRNA expression and activity in these neointimal lesions were significantly increased in hCRP-Tg rabbits as compared with non-Tg rabbits. The degree of CRP deposition correlated with the elevated TF expression and thrombus size on injured neointima. In addition, hCRP isolated from hCRP-Tg rabbit plasma induced TF mRNA expression and activity in rabbit cultured vascular SMCs.. These results suggest that elevated plasma hCRP levels promote thrombus formation on injured SMC-rich neointima by enhancing TF expression, but have no additive effects in macrophage-rich neointima.

Topics: Animals; Animals, Genetically Modified; C-Reactive Protein; Catheterization; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Femoral Artery; Humans; Hyperlipidemias; Macrophages; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Rabbits; RNA, Messenger; Thromboplastin; Thrombosis; Time Factors; Tunica Intima; Up-Regulation; Vascular System Injuries

Tissue factor (TF)-induced thrombin generation (TG) ex vivo has been suggested to be an important method to assess thrombotic risk. No studies have investigated the impact of postprandial lipemia on TF-induced TG. Since myocardial infarction (MI) is associated with elevated postprandial levels of triglycerides, we hypothesized a differential impact of postprandial lipemia on coagulation activation in MI-patients and healthy controls.. Elderly survivors of acute MI (n=44) and healthy age-and sex matched controls (n=43) underwent a fat tolerance test (1 gram per kg body weight) to assess coagulation activation during postprandial lipemia.. The incremental area under the curve (AUCi) for serum triglycerides was higher in MI-patients than in healthy age-and sex matched controls (5.64±0.52 mmol/L*h and 3.94±0.39 mmol/L*h, p=0.012) during the postprandial phase. Subsequent endogenous activation of coagulation, assessed by FVIIa and thrombin generation (F1+2), was similar among groups and not related to levels of triglycerides during the postprandial phase. Healthy individuals had a gradual decline in TF-induced thrombin generation ex vivo, assessed by endogenous thrombin potential (ETP) (AUCi=-542.4±71.4 nM*min*h, p<0.001), whereas MI-patients retained their ETP (AUCi=127.4±89.0 nM*min*h, p=0.47) in plasma during the postprandial phase (p for group difference=0.005).. MI-patients had elevated postprandial lipemia and retained their ability for TF-induced TG in plasma ex vivo in the postprandial phase, whereas the capacity gradually decreased in healthy individuals. Further studies are warranted to reveal underlying mechanism(s) and clinical implications.

Topics: Aged; Aged, 80 and over; Blood Coagulation; Fasting; Female; Humans; Hyperlipidemias; Male; Myocardial Infarction; Postprandial Period; Thrombin; Thromboplastin

Early growth response gene-1 (Egr-1) regulates the expression of genes important to cardiovascular disease. Within atherosclerotic lesions, Egr-1 is expressed in smooth muscle cells, endothelial cells, and macrophages. Since macrophages play a pivotal role in atherosclerotic lesion initiation and progression, this study investigated the effects of Egr-1 deficiency within bone marrow-derived cells on the development of atherosclerosis in a hyperlipidaemic mouse model.. Bone marrow from Egr-1-deficient mice and wild-type controls was transplanted into lethally irradiated LDL receptor null mice. After 26 weeks on a high fat diet, atherosclerotic lesion size within the aortic sinus of recipients was evaluated. Mice receiving Egr-1-deficient bone marrow had significantly decreased lesion size compared with controls. Lesions of these mice contained fewer macrophages and had reduced expression of vascular cell adhesion molecule-1 (VCAM-1), tissue factor, as well as transforming growth factor receptor type II, which are target genes of Egr-1. These results were validated by in vitro analysis of Egr-1-deficient peritoneal macrophages which, after lipopolysaccharide stimulation, had decreased VCAM-1 and tissue factor mRNA expression compared with wild-type controls.. This study demonstrates that bone marrow-derived Egr-1 promotes macrophage accumulation, atherosclerotic lesion development, and lesion complexity.

Topics: Animals; Aorta, Thoracic; Atherosclerosis; Bone Marrow Cells; Bone Marrow Transplantation; Disease Models, Animal; Early Growth Response Protein 1; Female; Gene Expression Regulation; Hyperlipidemias; Lipids; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Serine-Threonine Kinases; Radiation Chimera; Receptor, Transforming Growth Factor-beta Type II; Receptors, LDL; Receptors, Transforming Growth Factor beta; RNA, Messenger; Thromboplastin; Time Factors; Vascular Cell Adhesion Molecule-1; Whole-Body Irradiation

Tissue factor (TF), a transmembrane glycoprotein that acts as an essential cofactor to factor VII/VIIa, initiates the exogenous blood coagulation cascade leading to thrombin generation and subsequent thrombus formation in vivo. TF expression is closely related to plaque vulnerability, and high TF expression is shown in macrophage-rich atheromatous lesions, making TF a potential target for detecting atheromatous lesions in vivo. Thus, we prepared (99m)Tc-labeled anti-TF-monoclonal antibody (TF-mAb) IgG as a molecular probe and evaluated its usefulness to achieve TF-specific imaging using myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits.. Anti-TF-mAb was created using a standard hybridoma technique and was labeled by (99m)Tc with 6-hydrazinonicotinic acid (HYNIC) as a chelating agent to obtain (99m)Tc-TF-mAb. The immunoreactivity of HYNIC-TF-mAb was estimated by flow cytometry. WHHLMI and control rabbits were injected intravenously with (99m)Tc-TF-mAb. Twenty-four hours after the injection, the aorta was removed and radioactivity was measured. Autoradiography and histologic studies were performed using serial aorta sections. Subclass matched antibody (IgG(1)) was used as a negative control.. HYNIC-TF-mAb showed 93% immunoreactivity of the anti-TF-mAb. The radioactivity accumulation in WHHLMI aortas was 6.1-fold higher than that of control rabbits. Autoradiograms showed a heterogeneous distribution of radioactivity in the intima of WHHLMI aortas. Regional radioactivity accumulation was positively correlated with TF expression density (R = 0.64, P < 0.0001). The highest radioactivity accumulation in percentage injected dose × body weight/mm(2) × 10(2) was found in atheromatous lesions (5.2 ± 1.9) followed by fibroatheromatous (2.1 ± 0.7), collagen-rich (1.8 ± 0.7), and neointimal lesions (1.8 ± 0.6). In contrast, (99m)Tc-IgG(1) showed low radioactivity accumulation in WHHLMI aortas that was independent of the histologic grade of lesions.. The TF-detecting ability and preferential accumulation in atheromatous lesions of (99m)Tc-TF-mAb were demonstrated, indicating its potential for selective imaging of macrophage-rich atheromatous lesions in vivo.

Topics: Animals; Antibodies, Monoclonal; Atherosclerosis; Autoradiography; Flow Cytometry; Hydrazines; Hyperlipidemias; Immunoglobulin G; Male; Molecular Probes; Nicotinic Acids; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Regression Analysis; Technetium Compounds; Thromboplastin; Tissue Distribution

Arterial thrombosis occurs in atherosclerotic, but rarely in non-atherosclerotic arteries. The present study investigates how hyperlipidemic condition affects thrombus formation on macrophage-rich neointima or normal intima in rabbits. Rabbits were fed with a 0.5% cholesterol diet, and then the femoral artery on one side of each rabbit was injured with a balloon catheter. Three weeks later, bilateral femoral arteries were similarly injured with a balloon catheter to produce thrombi on neointima and normal intima. We compared the expression and activity of intimal tissue factor (TF) as well as thrombus size and composition between these femoral arteries. 0.5% cholesterol diet combined with a balloon injury induced macrophage-rich neointima in injured arteries. The whole blood coagulation activity or plasma thrombin generation activity did not differ after consuming the 0.5% cholesterol diet for 4 weeks, and an anti-TF antibody did not affect the measured parameters. TF activities were increased in the neointima/media compared with normal intima/media. Balloon injury induced large platelet-fibrin thrombi on macrophage-rich neointima, whereas small platelet thrombi were produced in normal arteries even under hyperlipidemic conditions. Recombinant human tissue factor pathway inhibitor (25microg/(kgmin)) and argatroban (100microg/(kgmin)), a specific thrombin inhibitor, significantly reduced thrombus formation on induced neointima, but not on normal intima. Thrombin generation mediated by TF in intima contributes to thrombus formation on macrophage-rich neointima, but not on normal intima. The TF content in disrupted atherosclerotic plaques might play a more important role than hyperlipidemia in the development of atherothrombosis.

Topics: Angioplasty, Balloon; Animals; Arginine; Femoral Artery; Humans; Hyperlipidemias; Lipoproteins; Macrophages; Male; Pipecolic Acids; Rabbits; Sulfonamides; Thrombin; Thromboplastin; Thrombosis; Tunica Intima

Changes in plasma tissue factor (TF)-activated factor VII (FVIIa) and plasma tissue factor pathway inhibitor (TFPI) in type II diabetes mellitus are assessed, vascular complicated and noncomplicated patients compared, and whether these novel hemostatic activity markers predict vascular complications in diabetic patients, improving risk assessment, is determined. Fifty type II diabetic patients and 20 healthy controls (age, sex and body mass matched) underwent medical history and examination, fasting plasma glucose level, glycosylated hemoglobin (HbA1c), lipid profile, hemostatic parameters, plasma TF activity, and TFPI and TF expression on blood monocytes. Mean TF, TF activity, TFPI, and FVIIa significantly increased among hyperlipidemic compared with normolipidemic diabetic patients, and normolipidemic diabetic patients compared with controls. Mean percentage TF-positive monocytes with and without lipopolysaccharide, plasma TF activity, TFPI and FVIIa were significantly higher among complicated than noncomplicated diabetic patients. Mean percentage TF-positive monocytes without and with lipopolysaccharide, plasma TF activity, plasma TFPI and FVIIa were higher among diabetic patients with macrovascular compared with microvascular complications. High significant correlation occurred between HbA1c, triglycerides and percentage TF-positive monocytes with and without lipopolysaccharide stimulation, plasma TF activity and both FVIIa and TFPI. High activity levels of plasma TF and FVIIa with increased circulating TF-positive monocytes occurred in type II diabetic patients, especially with vascular complications. Results reflect high procoagulant activity possibly involved in diabetic vascular complications. Elevated TFPI levels were observed, but were not sufficient to balance high procoagulant activity. Correlation of procoagulant activity markers with HbA1c reinforces the importance of optimal glycemic control in type II diabetes.

Topics: Adult; Aged; Case-Control Studies; Diabetes Complications; Diabetes Mellitus, Type 2; Factor VIIa; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Lipoproteins; Male; Middle Aged; Monocytes; Thromboplastin

In patients with chronic hypercholesterolemia, the CD40-CD40L dyad is upregulated, contributing to the initiation and progression of atherosclerosis. Our aim was to describe the role of postprandial lipemia and inflammatory stimulation on platelet and monocyte activation and CD40-ligand (CD40L) levels.. Before and 2 h after consumption of a defined fatty meal, whole blood samples of 31 healthy subjects were incubated with endotoxin (LPS). CD40-ligand and CD62P expression on platelets, tissue-factor expression on monocytes and platelet-monocyte aggregates were measured with flow cytometry. Soluble CD40-ligand plasma levels were measured with an ELISA. After the meal, serum triglyceride levels increased from 137.6+/-60.5 mg/dl to 201.5+/-75.0 mg/dl. Expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. No significant changes after the meal were observed concerning tissue factor expression on monocytes and platelet-monocyte aggregates. Addition of LPS showed no significant effect concerning CD40L or CD62P expression on platelets, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal.. Acute alimenatry lipemia leads to a decreased expression of CD40L on platelets and a reduced plasma level of sCD40L, suggesting an increased turnover in the CD40L system.. Before and after a fatty meal, blood samples of 31 healthy subjects were incubated with LPS. After the meal, expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. Addition of LPS showed no effect concerning CD40L or CD62P expression, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal.

Topics: Adult; Aged; Blood Platelets; CD40 Antigens; CD40 Ligand; Female; Gene Expression Regulation; Humans; Hypercholesterolemia; Hyperlipidemias; Inflammation; L-Selectin; Lipopolysaccharides; Male; Middle Aged; Postprandial Period; Thromboplastin

The inverse association of peanut consumption and risk markers of CHD (lipids) has been reported however health professionals are still concerned whether hyperlipidemic subjects advised to eat peanuts will have increased serum lipid levels. Tissue factor (TF), the major regulator of normal haemostasis and thrombosis, plays a critical role in haemostasis in all tissues.. To investigate the effects of peanut consumption on lipid profile, blood Glutathione (GSH), thiobarbituric acid reactive substances (TBARS), haematologic parameters and TF activities in rats fed a high-cholesterol diet.. 32 Wistar Albino rats were divided into 4 groups of 8 rats each: 1-Control 2-Control+peanut 3-Hyperlipidemic and 4-Hyperlipidemic+peanut group. At the end of 12 weeks, blood samples were used to evaluate lipid profile, haemostatic parameters, GSH, TBARS and tissue samples were used for the determination of TF activities.. Peanut consumption increased blood GSH both in the control and hyperlipidemic groups; increased HDL-cholesterol and decreased TBARS in the hyperlipidemic group. The addition of peanut to the diet did not change blood lipids, prothrombin time, activated partial thromboplastin time or fibrinogen levels significantly both in the control and hyperlipidemic groups. It affected TF activities differently in both groups. It decreased brain and aorta TF activity but increased spleen and kidney TF activity in the control group. It led to significant increases in the TF activity of kidney, spleen and aorta and a significant decrease in the TF activity of brain in the hyperlipidemic group.. Peanut consumption improved GSH and HDL-C levels and decreased TBARS, without increasing other blood lipids in experimental hyperlipidemia. Nevertheless the mechanism of the effect of peanut consumption on the TF activity of tissues remains to be determined.

Topics: Animals; Arachis; Cholesterol, Dietary; Cholesterol, HDL; Glutathione; Hemostasis; Hyperlipidemias; Lipid Metabolism; Random Allocation; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Thromboplastin

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Atorvastatin; Cohort Studies; Coronary Disease; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipids; Lipoproteins; Male; Middle Aged; Prothrombin; Pyrroles; Thrombin; Thromboplastin; Treatment Outcome

Several studies suggest a role for an increased circulating pool of tissue factor (TF) in atherothrombotic diseases. Furthermore, certain cardiovascular risk factors, such as diabetes, hyperlipemia, and smoking, are associated with a higher incidence of thrombotic complications. We hypothesized that the observed increased blood thrombogenicity (BT) observed in patients with type 2 diabetes mellitus may be mediated via an increased circulating tissue factor activity. We have extended our study to smokers and hyperlipidemic subjects.. Poorly controlled patients with type 2 diabetes mellitus (n=36), smokers (n=10), and untreated hyperlipidemic subjects (n=10) were studied. Circulating TF was immunocaptured from plasma, relipidated, and quantified by factor Xa (FXa) generation in the presence of factor VIIa. BT was assessed as thrombus formation on the Badimon perfusion chamber. Patients with improvement in glycemic control showed a reduction in circulating TF (362+/-135 versus 243+/-74 pmol/L per min FXa, P=0.0001). A similar effect was observed in BT (15 445+/-1130 versus 12 072+/-596 microm/mm2, P=0.01). Two hours after smoking 2 cigarettes, TF was increased (217+/-72 versus 283+/-106 pmol/L per min FXa, P=0.003). Hyperlipidemic subjects showed higher TF (237+/-63 versus 195+/-44 pmol/L per min FXa, P=0.035) than healthy volunteers.. These findings suggest that high levels of circulating TF may be the mechanism of action responsible for the increased thrombotic complications associated with the presence of these cardiovascular risk factors. These observations strongly emphasize the usefulness of the management of the patients based on their global risk assessment.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipidemias; Male; Middle Aged; Risk Factors; Smoking; Thromboplastin; Thrombosis

Topics: Anticholesteremic Agents; Antineoplastic Agents; Apolipoproteins; Biomarkers; C-Reactive Protein; Coronary Disease; Female; Fibrinogen; Hemostatics; Humans; Hyperlipidemias; Lipoproteins; Male; Matrix Metalloproteinase 9; Middle Aged; Placebo Effect; Protease Inhibitors; Simvastatin; Thromboplastin; Thrombosis; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha

Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001

Topics: Adult; Age Factors; Antigens; Body Mass Index; Body Weight; Chemokine CCL2; Factor VII; Female; Humans; Hyperlipidemias; Lipids; Lipopolysaccharides; Lipoproteins; Male; Middle Aged; Monocytes; Thromboplastin

We measured plasma levels of tissue factor (TF), total tissue factor pathway inhibitor (TFPI) and free TFPI antigen in patients with diabetes mellitus (DM), hyperlipidemia and disseminated intravascular coagulation (DIC). The mean TF, total TFPI and free TFPI antigen concentrations were significantly higher in patients with DM than in controls and the plasma TF concentration was significantly higher in patients with retinopathy or nephropathy than in DM with no complications. The mean TF, total TFPI and free TFPI antigen concentrations were significantly higher in patients with hyperlipidemia than in controls. There was a significant positive correlation between levels of total TFPI and total cholesterol. In patients with hyperlipidemia, the level of total TFPI was significantly decreased compared to base line level by cholesterol lowering drug, however, free TFPI concentration did not change by cholesterol lowering drug. The TF and total TFPI concentrations were significantly higher in patients with DIC than in controls.

Topics: Anticoagulants; Antigens; Biomarkers; Cholesterol; Diabetes Mellitus; Disseminated Intravascular Coagulation; Humans; Hyperlipidemias; Lipoproteins; Thromboplastin

The relationship of triglyceride levels to coagulation abnormalities was studied in 43 patients, who were divided into two groups. Group 1 consisted of patients with triglyceride levels less than 200 mg% (range, 75 to 190 mg%), and Group 2 consisted of patients with triglyceride levels greater than 250 mg% (range, 255 to 890 mg%). Analysis of the data revealed that patients with high triglyceride levels also have a high incidence of low antithrombin III activity and increased platelet aggregation. It is likely that hyperlipidemic patients are more prone to thrombosis of diseased coronary arteries or saphenous vein bypass grafts, and should definitely be placed on appropriate anticoagulants.

Topics: Adult; Aged; Anticoagulants; Antithrombin III; Blood Coagulation Disorders; Coronary Disease; Female; Fibrinogen; Humans; Hyperlipidemias; Male; Middle Aged; Platelet Aggregation; Prospective Studies; Thromboplastin; Thrombosis; Triglycerides

Topics: Adenosine Diphosphate; Adult; Blood Coagulation Tests; Collagen; Epinephrine; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Male; Middle Aged; Platelet Adhesiveness; Platelet Aggregation; Platelet Factor 4; Serotonin; Thromboplastin; von Willebrand Factor

Topics: Adult; Blood Cell Count; Blood Coagulation Factors; Blood Platelets; Blood Protein Electrophoresis; Calcium; Cholesterol; Chromatography, Gas; Chromatography, Thin Layer; Dietary Fats; Fatty Acids, Nonesterified; Female; Humans; Hyperlipidemias; Lipids; Lipoproteins; Male; Middle Aged; Palmitic Acids; Phospholipids; Stearic Acids; Thromboplastin; Triglycerides

Topics: Blood Coagulation; Humans; Hyperlipidemias; Lipoproteins; Thromboplastin

Topics: Acidosis; Adrenocorticotropic Hormone; Animals; Antibodies; Anticoagulants; Antigens; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Volume; Colloids; Cortisone; Endotoxins; Female; Fibrinolysis; Fluorescent Antibody Technique; Hemolysis; Humans; Hyperlipidemias; Kidney Cortex Necrosis; Leukocytes; Mononuclear Phagocyte System; Norepinephrine; Peptide Hydrolases; Phagocytosis; Phenoxybenzamine; Pregnancy; Rabbits; Shwartzman Phenomenon; Sympatholytics; Thromboplastin

Topics: Arteriosclerosis; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Extracorporeal Circulation; Fibrin; Fibrinolysis; Hemorrhage; Heparin; Heparin Antagonists; Humans; Hyperlipidemias; Hypersensitivity; Natriuresis; Osteoporosis; Protamines; Prothrombin Time; Thromboembolism; Thrombophlebitis; Thromboplastin

Topics: Adult; Antithrombins; Blood Coagulation Tests; Factor V Deficiency; Factor VIII; Humans; Hyperlipidemias; Hypoprothrombinemias; Middle Aged; Thrombelastography; Thromboplastin