RSS-Feed abonnieren
DOI: 10.1160/TH14-02-0156
Hypercoagulability in overweight and obese subjects who are asymptomatic for thrombotic events
Publikationsverlauf
Received:
19. Februar 2014
Accepted after major revision:
04. September 2014
Publikationsdatum:
27. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201501/lookinside/thumbnails/10-1160-th-14-02-0156-1.jpg)
Summary
The role of circulating microparticles (MP) of different origin and tissue factor (TF)-bearing in overweight and obese patients with and without metabolic syndrome is still a matter of debate. In a case-control study, the presence of hypercoagulability was evaluated in overweight and obese patients by measuring MP, thrombin generation (TG) and FVIIa-AT complexes. Twenty overweight patients (body mass index [BMI] range 25–29.9 kg/m2), 20 with I degree (30–34.9 kg/m2), 20 with II degree (35–39.9 kg/m2) and 20 with III degree obesity (≥ 40 kg/m2) were enrolled and compared to 40 age and gender-matched normal weight individuals. A significant increase in median levels of all MP subtypes was observed in the three degrees of obese patients compared to controls. Overweight patients had higher levels of annexin V-MP (AMP), endothelial-derived, leukocyte-derived and TF-bearing MP than controls. Obese patients had a significantly shorter median lag time (p< 0.05), higher median peak thrombin (p< 0.01) and increased median endogenous thrombin potential [ETP] (p< 0.001) compared to controls. Overweight subjects had significantly increased ETP compared to controls (p< 0.05). Both AMP levels and ETP were found to positively correlate with BMI, waist circumference, and inflammatory parameters. No significant increase in FVIIa-AT complex was seen in cases compared to controls. We conclude that obesity is associated with overproduction of procoagulant MP and increase TG. Interestingly, hypercoagulability is found in overweight patients free of metabolic syndrome and increases with the severity of obesity. Assessment of MP and TG may be helpful in the early characterisation of the prothrombotic state in obese patients.
* These authors equally contributed to the study.
-
References
- 1 Darvall KAL, Sam RC, Silverman SH. et al. Obesity and thrombosis. Eur J Vasc Endovasc Surg 2007; 33: 223-233.
- 2 Lorenzet R, Napoleone E, Cutrone A. et al. Thrombosis and obesity: cellular bases. Thromb Res 2012; 129: 285-289.
- 3 Rosito GA, D’Agostino RB, Massaro J. et al. Association between obesity and a prothrombotic state: the Framingham Offspring Study. Thromb Haemost 2004; 91: 683-689.
- 4 Reaven GM, Scott EM, Grant PJ. et al. Hemostatic abnormalities associated with obesity and the metabolic syndrome. J Thromb Haemost 2005; 03: 1074-1085.
- 5 Mertens I, Van Gaal LF. Obesity, haemostasis and the fibrinolytic system. Obes Rev 2002; 03: 85-101.
- 6 Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood 2013; 122: 3415-3422.
- 7 Piccin A, Murphy WG, Smith OP. Circulating microparticles: pathophysiology and clinical implications. Blood Rev 2007; 21: 157-171.
- 8 Owens III AP, Mackman N. Microparticles in Hemostasis and Thrombosis. Circ Res 2011; 108: 1284-1297.
- 9 Burger D, Schock S, Thompson CS. et al. Microparticles: biomarkers and beyond. Clin Sci 2013; 124: 423-441.
- 10 Boulanger CM, Dignat-George F. Microparticles: an introduction. Arterioscler Thromb Vasc Biol 2011; 31: 2-3.
- 11 Manly DA, Wang J, Glover SL. et al. Increased microparticle tissue factor activity in cancer patients with venous thromboembolism. Thromb Res 2010; 125: 511-512.
- 12 Furie B, Furie BC. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol Med 2004; 10: 171-178.
- 13 Morel O, Toti F, Hugel B. et al. Procoagulant microparticles: disrupting the vascular homeostasis equation?. Arterioscler Thromb Vasc Biol 2006; 26: 2594-2604.
- 14 Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008; 359: 938-949.
- 15 Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004; 104: 3190-3197.
- 16 Falati S, Liu Q, Gross P. et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin Glycoprotein Ligand 1 and platelet P-selectin. J Exp Med 2003; 197: 1585-1598.
- 17 Ye R, Ye C, Huang Y. et al. Circulating tissue-factor positive microparticles in patients with acute recurrent deep vein thrombosis. Thromb Res 2012; 130: 253-258.
- 18 Ay C, Freyssinet JM, Salier T. et al. Circulating procoagulant microparticles in patients with venous thromboembolism. Thromb Res 2009; 123: 724-726.
- 19 Shantsila E, Kamphuisen PW, Lip GY. Circulating microparticles in cardiovascular disease: implications for atherogenesis and atherothrombosis. J Thromb Haemost 2010; 08: 2358-2368.
- 20 Gross PL, Furie BC, Merrill-Skoloff G, Chou J, Furie B. Leukocyte-versus micro-particle-mediated tissue factor transfer during arteriolar thrombus development. J Leukoc Biol 2005; 78: 1318-1326.
- 21 Suades R, Padró T, Vilahur G. et al. Circulating and platelet-derived microparticles in human blood enhance thrombosis on atherosclerotic plaques. Thromb Haemost 2012; 108: 1208-1219.
- 22 Namba M, Tanaka A, Shimada K. et al. Circulating platelet-derived microparticles are associated with atherothrombotic events: a marker for vulnerable blood. Arterioscler Thromb Vasc Biol 2007; 27: 255-256.
- 23 Goichot B, Grunebaum L, Desprez D. et al. Circulating procoagulant microparticles in obesity. Diabetes Metab 2006; 32: 82-85.
- 24 Morel O, Luca F, Grunebaum L. Short-term very low-calorie diet in obese females improves the haemostatic balance through the reduction of leptin levels, PAI-1 concentrations and a diminished release of platelet and leukocyte-derived microparticles. Int J Obes 2011; 35: 1479-1486.
- 25 Murakami T, Horigome H, Tanaka K. et al. Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity. Thromb Res 2007; 119: 45-53.
- 26 Esposito K, Ciotola M, Schisano B. et al. Endothelial microparticles correlate with endothelial dysfunction in obese women. J Clin Endocrinol Metab 2006; 91: 3676-3679.
- 27 Csongrádi É, Nagy Jr B, Fulop T. et al. Increased levels of platelet activation markers are positively associated with carotid wall thickness and other athero-sclerotic risk factors in obese patients. Thromb Haemost 2011; 106: 683-692.
- 28 Moore XL, Michell D, Lee S. et al. Increased carotid intima-media thickness and reduced distensibility in human class III obesity: independent and differential influences of adiposity and blood pressure on the vasculature. PLoS One 2013; 08: e53972.
- 29 Helal O, Defoort C, Robert S. et al. Increased levels of Microparticles originating from endothelial cells, platelets and erithrocytes in subjects with metabolic syndrome: relationship with oxidative stress. Nutr Metab Cardiovasc Dis 2011; 21: 665-671.
- 30 Stepanian A, Bourguignat L, Hennou S. et al. Microparticle increase in severe obesity: not related to metabolic syndrome and unchanged after massive loss. Obesity 2013; 21: 2236-2243.
- 31 Lacroix R, Dubois C, Leroyer AS. et al. Revisited role of microparticles in arterial and venous thrombosis. J Thromb Haemost 2013; 11: 24-35.
- 32 ten Cate H. Thrombin generation in clinical conditions. Thromb Res 2012; 129: 367-370.
- 33 Spiezia L, Rossetto V, Campello E. et al. Factor VIIa-Antithrombin Complexes in Patients with Arterial and Venous Thrombosis. Thromb Haemost 2010; 103: 1188-1192.
- 34 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419.
- 35 Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). J Am Med Assoc 2001; 285: 2486-2497.
- 36 Koutroumpi S, Spiezia L, Albiger N. et al. Thrombin generation in Cushing’s Syndrome: do the conventional clotting indices tell the whole truth?. Pituitary 2014; 17: 68-75.
- 37 Campello E, Spiezia L, Radu CM. et al. Endothelial, platelet and tissue factor-bearing microparticles in cancer patients with and without venous thrombembolism. Thromb Res 2011; 127: 473-477.
- 38 Campello E, Spiezia L, Radu CM. et al. Circulating microparticles in carriers of factor V Leiden with and without a history of venous thrombosis. Thromb Hae-most 2012; 108: 633-639.
- 39 Lacroix R, Robert S, Poncelet P. et al. Standardization of platelet-derived micro-particle enumeration by flow cytometry with calibrated beads: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost 2010; 08: 2571-2574.
- 40 Lacroix R, Judicone C, Mooberry M. et al. Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost 2013; 11: 1190-1193.
- 41 van Dreden P, Rousseau A, Fontaine S. et al. Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids. Blood Coag Fibrinolysis 2009; 20: 494-502.
- 42 Campello E, Spiezia L, Radu CM. et al. Evaluation of a procoagulant phosholipid functional assay as a routine test for measuring circulating microparticle activity. Blood Coagul Fibrinolysis 2014; 25: 534-537.
- 43 De Pergola G, Pannacciulli N. Coagulation and fibrinolyses abnomalities in obesity. J Endocrinol Invest 2002; 25: 899-904.
- 44 Cimenti C, Mangge H, Haidl H. et al. Thrombin generation in severely obese children. J Thromb Haemost 2006; 04: 1834-1836.
- 45 Chen M, Geng JG. P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp 2006; 54: 75-84.
- 46 Khew-Goodall Y, Butcher CM, Litwin MS. et al. Chronic expression of P-selectin on endothelial cells stimulated by the T-cell cytokine, interleukin-3. Blood 1996; 87: 1432-1438.
- 47 Schafer K, Konstantinides S. Adipokines and thrombosis. Clin Exp Pharmacol Physiol 2011; 38: 864-871.
- 48 Prüller F, Raggam RB, Posch V. et al. Trunk weighted obesity, cholesterol levels and low grade inflammation are main determinants for enhanced thrombin generation. Atherosclerosis 2012; 220: 215-218.
- 49 Badimon L, Storey RF, Vilahur G. Update on lipids, inflammation and atherothrombosis. Thromb Haemost 2011; 105: S34-S42.
- 50 Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415-445.
- 51 Zhang X, McGeoch SC, Johnstone AM. et al. Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status. J Thromb Thrombolysis 2014; 37: 455-463.
- 52 Tian YF, Chang WC, Loh CH, Hsieh PS. Leptin-mediated inflammatory signaling crucially links visceral fat inflammation to obesity-associated -cell dys-function. Life Sci. 2014 Epub ahead of print.
- 53 Sanchez C, Poggi M, Morange PE. et al. Diet modulates endogenous thrombin generation, a biological estimate of thrombosis risk, independently of the metabolic status. Arterioscler Thromb Vasc Biol 2012; 32: 2394-2404.
- 54 Gheldof D, Hardij J, Cecchet F. et al. Thrombin generation assay and transmission electron microscopy: a useful combination to study tissue factor-bearing microvesicles. J Extracell Vesicles 2013; 02: 19728.
- 55 Connor DE, Exner T, Ma DD. et al. The majority of circulating platelet-derived microparticles fail to bind annexin V, lack phospholipid-dependent procoagulant activity and demonstrate greater expression of glycoprotein Ib. Thromb Haemost 2010; 103: 1044-1052.