thromboplastin and Weight-Loss

In obesity, metabolic stress and inflammation in injured tissues could favour enhanced shedding of procoagulant microparticles (MPs). At sites of endothelium injury, the swift recruitment of procoagulant leukocyte-derived MPs enables the initiation of blood coagulation and thrombus growth.. In obese females, we sought to evaluate the impact of a very low-calorie diet (VLCD) on procoagulant MP levels, fibrinolytic status, inflammation and endothelium damage.. Circulating biomarkers of vascular damage, fibrinolytic status, platelet activation and inflammation were measured before, 30 and 90 days after starting a short-term VLCD. MPs were measured by flow cytometry and capture assays. Their procoagulant potential was quantified using functional prothrombinase assays and their cellular origin were determined using flow cytometry (endothelium, platelet, leukocyte, lymphocyte and erythrocyte-derived MP) or capture assays.. A total of 24 obese females (39 ± 10 years) with a mean body mass index of 35 ± 4  kg m(-2) were prospectively enroled. Procoagulant leukocyte-derived MPs were associated with the waist circumference at baseline (r=0.534; P=0.010) and at 90 days follow-up (r=0.487; P=0.021). At 90 days, weight reduction (-9.8%) was associated with a lowering of blood pressure, improvement of metabolic parameters and a significant reduction of plasminogen activator inhibitor-1 (PAI-1) (-38%), procoagulant platelet-derived MPs (-43%), leukocyte-derived MPs (-28%) and leptin (-32%) levels.. In obese females, a short-term VLCD results in an overall improvement of the haemostatic balance characterized by the reduction of PAI-levels, diminished release of platelet and leukocyte-derived MPs and a reduction in leptin levels, an adipocyte-derived cytokine.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Coagulation Factors; Blood Platelets; Caloric Restriction; Endothelium, Vascular; Erythrocytes; Female; Hemostasis; Humans; Leptin; Leukocytes; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Prospective Studies; Thromboplastin; Thrombosis; Weight Loss; Young Adult

Tissue factor (TF) is the main in vivo initiator of the blood coagulation cascade. Active circulating TF was detected on small, negatively charged membrane vesicles, the so-called microvesicles (MVs), which are released upon cell activation and apoptosis from a variety of cells. Increased coagulation activation was found in morbidly obese patients, and elevated levels of TF-bearing MVs may contribute to the prothrombotic state in these patients.. To determine MV-associated TF activity levels in morbidly obese patients before and after weight loss due to bariatric surgery.. MV-TF activity was measured with a factor Xa generation assay in morbidly obese patients before and 2 years after bariatric surgery. In addition, clinical parameters were determined.. Seventy-four morbidly obese patients (mean age: 42 (±11) years; 61 females) were included in this study. After bariatric surgery, the body mass index decreased from (median, 25-75th percentile) 45.5 (42.3-50.2) to 30.5 (28.0-34.4 kg m(-2); P<0.001), and a significant improvement in metabolic parameters was observed. Preoperative MV-TF activity correlated with C-reactive protein levels (r=0.3; P=0.02). Postoperatively, the mean MV-TF activity decreased significantly from 0.20 pg ml(-1) (0.18-0.47) to 0.02 (0.00-0.28; P<0.01).. We could demonstrate a significant decrease in MV-TF activity after weight loss in morbidly obese patients. Decreased MV-TF activity might contribute to an improved coagulation profile in these patients after weight loss.

Topics: Adult; Austria; Bariatric Surgery; Biomarkers; Blood Coagulation; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Down-Regulation; Female; Humans; Longitudinal Studies; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Prospective Studies; Thromboplastin; Treatment Outcome; Weight Loss

Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (-30.5%) the thrombin generation potential in plasma evaluated upon extrinsic (TF/FVIIa pathway) but not intrinsic activation of coagulation. This variation was consistent with a decrease (-49.8%) in the plasma activity levels of factor VII (FVII), the crucial physiologicalal trigger of coagulation, which was even more pronounced at the liver mRNA level (-85.7%). The recovery in normal sleep conditions for three days completely restored thrombin generation and FVII activity in plasma. For the first time, we demonstrate that chronic sleep deprivation on its own reduces, in a reversible manner, the FVII expression levels, thus influencing the TF/FVIIa activation pathway efficiency.

Topics: Animals; Chronic Disease; Factor VII; Factor VIIa; Gene Expression Regulation; Mice; Mice, Inbred C57BL; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Sleep Deprivation; Thrombin; Thromboplastin; Time Factors; Weight Loss

To investigate the tissue factor (TF) pathway in clinical obesity and associated metabolic syndrome.. Thirty-seven morbidly obese patients (4 men; BMI, 48 +/- 7 kg/m(2); range, 42 to 53 kg/m(2)), undergoing elective gastroplasty for the induction of weight loss, were examined for hemostatic, metabolic, and inflammatory parameters at baseline and 14 +/- 5 months postoperatively.. Weight loss significantly reduced circulating plasma TF (314 +/- 181 vs. 235 +/- 113 pg/mL, p = 0.04), coagulation factor VII (130 +/- 22% vs. 113 +/- 19%, p = 0.023), and prothrombin fragment F1.2 (2.4 +/- 3.4 vs. 1.14 +/- 1.1 nM, p = 0.04) and normalized glucose metabolism in 50% of obese patients preoperatively classified as diabetic or of impaired glucose tolerance. The postoperative decrease in plasma TF correlated with the decrease of F1.2 (r = 0.56; p = 0.005), a marker of in vivo thrombin formation. In subgroup analysis stratified by preoperative glucose tolerance, baseline circulating TF (402.6 +/- 141.6 vs. 176.2 +/- 58.2, p < 0.001) and TF decrease after gastroplasty (DeltaTF: 164.7 +/- 51.4 vs. -81 +/- 31 pg/mL, p = 0.02) were significantly higher in obese patients with impaired glucose tolerance than in patients with normal glucose tolerance.. Procoagulant TF is significantly reduced with weight loss and may contribute to a reduction in cardiovascular risk associated with obesity.

Topics: Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Factor VII; Female; Gastroplasty; Glycated Hemoglobin; Humans; Insulin; Interleukin-6; Leptin; Lipoproteins; Longitudinal Studies; Male; Obesity, Morbid; Prospective Studies; Prothrombin Time; Statistics, Nonparametric; Thromboplastin; Transforming Growth Factor beta; Weight Loss

To investigate whether impaired endothelial function was related to alteration of nitric oxide (NO) formation during endotoxic shock, we studied the effects of supplementation of L-arginine (L-Arg), D-arginine (D-Arg), and N(G)-nitro-L-arginine methyl ester (L-NAME), on endothelial function and structure in a rabbit model. Endotoxic shock was induced by a single lipopolysaccharide bolus (0.5 mg/kg i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor were determined by functional assays. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess damaged endothelial cell surface of the abdominal aorta. These parameters were studied 5 days after the onset of endotoxic shock and were compared under three conditions: in absence of treatment, with L-Arg or D-Arg supplementation, or with L-NAME. Both L-Arg and D-Arg significantly improved endothelium-dependent relaxation and endothelial morphological injury. L-NAME did not alter endothelial histological injury induced by lipopolysaccharide. These data indicate that arginine supplementation nonspecifically prevents endothelial dysfunction and histological injury in rabbit endotoxic shock. Moreover, L-Arg has no effect on coagulation activation and expression of monocyte tissue factor induced by endotoxic shock.

Topics: Acetylcholine; Animals; Arginine; Blood Gas Analysis; Calcimycin; Disease Models, Animal; Endothelium, Vascular; Enzyme Inhibitors; Hemostasis; Ionophores; Lipopolysaccharides; Male; Monocytes; NG-Nitroarginine Methyl Ester; Nitroprusside; Phenylephrine; Rabbits; Shock, Septic; Thromboplastin; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Weight Loss