Body mass index reduction improves the baseline procoagulant imbalance of obese subjects

  • Armando TripodiEmail author
  • Massimo Primignani
  • Sara Badiali
  • Fausto de Ruberto
  • Paola Granelli
  • Giulia Tosetti
  • Marigrazia Clerici
  • Lidia Padovan
  • Veena Chantarangkul
  • Erica Scalambrino
  • Flora Peyvandi


Obesity is a risk factor for cardiovascular diseases. The latter being dependent (at least in part) on plasma procoagulant imbalance (i.e., hypercoagulability). Information on hypercoagulability associated with obesity is scanty and mainly based on global traditional coagulation tests or on the measurement of individual components of coagulation (i.e., pro- and anticoagulants). Plasma from 33 obese subjects was investigated soon before endoscopic balloon placement and after removal (6 months later) by thrombin-generation procedures that are thought to represent much better than any other in vitro test the coagulation process occurring in vivo. We found that obese subjects possess a state of hypercoagulability as demonstrated by the modification of the main parameters of thrombin-generation. In particular, the median value (min–max) of the endogenous thrombin potential (ETP) of obese subjects at baseline was higher than that of controls [1968 (1335–2533) vs. 1710 (1010–2119), p < 0.001]. Endoscopic balloon placement achieved a BMI reduction from 38.9 (31.7–62.3) to 31.6 (21.9–53.3), p < 0.001 and a parallel reduction of thrombin-generation as demonstrated by the following findings. The ETP measured soon after balloon removal was significantly smaller than that measured at baseline [1783 (1224–2642) vs. 1968 (1335–2533), p < 0.01]. The other parameters of thrombin-generation, including lag-time, peak-thrombin, time-to-reach the peak and velocity index showed a pattern consistent with the ETP, both at baseline and soon after balloon removal. Endoscopic balloon placement achieves concomitant reduction of BMI and thrombin-generation in subjects with obesity.


Hypercoagulability Thrombin generation Endogenous thrombin potential Endoscopic balloon therapy Cardiovascular diseases 


Author contributions

AT and MP conceived and supervised the study. AT wrote the manuscript. SB, FdB and PG enrolled and managed patients. GT collected data. MC, LP, VC and ES, tested samples. VC managed data and made statistical analyses. FP and all the other authors reviewed data and revised the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    NCD Risk Factor Collaboration (NCD-RisC) (2016) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 387:1377–1396CrossRefGoogle Scholar
  2. 2.
    GBD 2015 Obesity Collaborators (2017) Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 377:13–27CrossRefGoogle Scholar
  3. 3.
    Ogden CL, Carroll MD, Kit BK, Flegal KM (2014) Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 311:806–814CrossRefGoogle Scholar
  4. 4.
    Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH, American Heart Association; Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113:898–918CrossRefGoogle Scholar
  5. 5.
    Stein PD, Goldman J (2009) Obesity and thromboembolic disease. Clin Chest Med 30:489–493CrossRefGoogle Scholar
  6. 6.
    Tripodi A, Chantarangkul V, Mannucci PM (2009) Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing. Br J Haematol 147:77–82CrossRefGoogle Scholar
  7. 7.
    Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R et al (2003) Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 33:4–15CrossRefGoogle Scholar
  8. 8.
    Frezzato M, Tosetto A, Rodeghiero F (1996) Validated questionnaire for the identification of previous personal or familial venous thromboembolism. Am J Epidemiol 143:1257–1265CrossRefGoogle Scholar
  9. 9.
    Chantarangkul V, Clerici M, Bressi C, Giesen PL, Tripodi A (2003) Thrombin generation assessed as endogenous thrombin potential in patients with hyper- or hypo-coagulability. Haematologica 88:547–554Google Scholar
  10. 10.
    Tripodi A, Primignani M, Chantarangkul V, Dell’Era A, Clerici M, de Franchis R et al (2009) An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 137:2105–2111CrossRefGoogle Scholar
  11. 11.
    Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P et al (2004) Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 117:19–25CrossRefGoogle Scholar
  12. 12.
    Tripodi A (2016) Thrombin generation assay and its application in the clinical laboratory. Clin Chem 62:699–707CrossRefGoogle Scholar
  13. 13.
    Vyas D, Deshpande K, Pandya Y (2017) Advances in endoscopic balloon therapy for weight loss and its limitations. World J Gastroenterol 23:7813–7817CrossRefGoogle Scholar
  14. 14.
    Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA (2006) Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 296:397–402CrossRefGoogle Scholar
  15. 15.
    van Hylckama Vlieg A, Christiansen SC, Luddington R, Cannegieter SC, Rosendaal FR, Baglin TP (2007) Elevated endogenou s thrombin po-tential is associated with an increased risk of a first deep venous thromb osis but not with the risk of recurrence. Br J Haematol 138:769–774CrossRefGoogle Scholar
  16. 16.
    Tripodi A, Legnani C, Chantarangkul V, Cosmi B, Palareti G, Mannucci PM (2008) High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 6:1327–1333CrossRefGoogle Scholar
  17. 17.
    Bucciarelli P, Martinelli I, Artoni A, Passamonti SM, Previtali E, Merati G et al (2012) Circulating microparticles and risk of venous thromboembolism. Thromb Res 129:591–597CrossRefGoogle Scholar
  18. 18.
    Tripodi A, Branchi A, Chantarangkul V, Clerici M, Merati G, Artoni A et al (2011) Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay. J Thromb Thrombolysis 31:165–172CrossRefGoogle Scholar
  19. 19.
    Goichot B, Grunebaum L, Desprez D, Vinzio S, Meyer L, Schlienger JL et al (2006) Circulating procoagulant microparticles in obesity. Diabetes Metab 32:82–85CrossRefGoogle Scholar
  20. 20.
    Kranendonk ME, de Kleijn DP, Kalkhoven E, Kanhai DA, Uiterwaal CS, van der Graaf Y, Pasterkamp G, Visseren FL, SMART Study Group (2014) Extracellular vesicle markers in relation to obesity and metabolic complications in patients with manifest cardiovascular disease. Cardiovasc Diabetol 5:13–37Google Scholar
  21. 21.
    Siklar Z, Öçal G, Berberoğlu M, Hacihamdioğlu B, Savas Erdeve S, Eğin Y et al (2011) Evaluation of hypercoagulability in obese children with thrombin generation test and microparticle release: effect of metabolic parameters. Clin Appl Thromb Hemost 17:585–589CrossRefGoogle Scholar
  22. 22.
    Murakami T, Horigome H, Tanaka K, Nakata Y, Ohkawara K, Katayama Y et al (2007) Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity. Thromb Res 119:45–53CrossRefGoogle Scholar
  23. 23.
    Campello E, Zabeo E, Radu CM, Spiezia L, Foletto M, Prevedello L et al (2016) Dynamics of circulating microparticles in obesity after weight loss. Intern Emerg Med 11:695–702CrossRefGoogle Scholar
  24. 24.
    Ambrósio G, Kaufmann FN, Manosso L, Platt N, Ghisleni G, Rodrigues ALS et al (2018) Depression and peripheral inflammatory profile of patients with obesity. Psychoneuroendocrinology 91:132–141CrossRefGoogle Scholar
  25. 25.
    Freitas WR Jr, Oliveira LVF, Perez EA, Ilias EJ, Lottenberg CP, Silva AS et al (2018) Systemic inflammation in severe obese patients undergoing surgery for obesity and weight-related diseases. Obes Surg. Google Scholar
  26. 26.
    Francisco V, Pino J, Gonzalez-Gay MA, Mera A, Lago F, Gómez R et al (2018) Adipokines and inflammation: is it a question of weight? Br J Pharmacol. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Armando Tripodi
    • 1
    Email author
  • Massimo Primignani
    • 2
  • Sara Badiali
    • 3
  • Fausto de Ruberto
    • 3
  • Paola Granelli
    • 3
  • Giulia Tosetti
    • 2
  • Marigrazia Clerici
    • 1
  • Lidia Padovan
    • 1
  • Veena Chantarangkul
    • 1
  • Erica Scalambrino
    • 1
  • Flora Peyvandi
    • 1
    • 4
  1. 1.IRCCS Cà Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi villaMilanoItaly
  2. 2.Division of Gastroenterology and HepatologyIRCCS Cà Granda Maggiore Hospital Foundation Milano, A.M. and A. Migliavacca Center for Liver DiseaseMilanoItaly
  3. 3.Divisione di Chirurgia GeneraleIRCCS Cà Granda Maggiore Hospital Foundation MilanoMilanoItaly
  4. 4.Department of Pathophysiology and TransplantationUniversità degli Studi di MilanoMilanoItaly

Personalised recommendations