Thromb Haemost 2014; 111(01): 88-93
DOI: 10.1160/TH13-01-0042
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients

Tzu-Fei Wang
1   Division of Hematology, Department of Medicine, The Ohio State University, Columbus, Ohio, USA
2   Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
Paul E. Milligan
2   Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
3   Center for Clinical Excellence, BJC HealthCare, Saint Louis, Missouri, USA
Catherine A. Wong
3   Center for Clinical Excellence, BJC HealthCare, Saint Louis, Missouri, USA
Eli N. Deal
4   Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, Missouri, USA
Mark S. Thoelke
2   Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
Brian F. Gage
2   Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
› Author Affiliations
Financial support: This study was funded in part by the BJC Center for Clinical Excellence and the NIH (R01 HL 097036).
Further Information

Publication History

Received: 16 January 2013

Accepted after major revision: 12 September 2013

Publication Date:
29 November 2017 (online)


Obesity increases the risk for venous thromboembolism (VTE), but whether high-dose thromboprophylaxis is safe and effective in morbidly obese inpatients is unknown. It was the objective of this study to quantify the efficacy and safety of high-dose thromboprophylaxis with heparin or enoxaparin in inpatients with weight > 100 kilograms (kg) within the BJC HealthCare system. In a retrospective cohort study, we analysed 9,241 inpatients with weight < 100 kg discharged from three hospitals in the BJC HealthCare system from 2010 through 2012. We compared the incidence of VTE in patients who received high-dose thromboprophylaxis (heparin 7,500 units three times daily or enoxaparin 40 mg twice daily) to those who received standard doses (heparin 5,000 units two or three times daily or enoxaparin 40 mg once daily). The primary efficacy outcome was hospital-acquired VTE identified by International Classification of Diseases (ICD)-9 diagnosis codes. The primary safety outcome was bleeding events identified by ICD-9 codes. Among the 3,928 morbidly obese inpatients (weight > 100 kg and body mass index [BMI] ≥ 40 kg/m2), high-dose thromboprophylaxis approximately halved the odds of symptomatic VTE (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.27–1.00; p = 0.050). The rate of VTE was 1.48% (35/2,369) in these morbidly obese inpatients who received standard doses of thromboprophylaxis, compared to 0.77% (12/1,559) in those who received high doses. High-dose thromboprophylaxis did not increase bleeding (OR 0.84, 95% CI 0.66–1.07, p = 0.15). Independent predictors of VTE were surgery, male sex, cancer, and BMI. In conclusion, high-dose thromboprophylaxis nearly halves the rate of VTE in morbidly obese inpatients.

  • References

  • 1 Wattanakit K, Lutsey PL, Bell EJ. et al. Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. Thromb Haemost 2012; 108: 508-515.
  • 2 Morange PE, Alessi MC. Thrombosis in central obesity and metabolic syndrome: Mechanisms and epidemiology. Thromb Haemost 2013; 110: 669-680.
  • 3 Goldhaber SZ, Grodstein F, Stampfer MJ. et al. A prospective study of risk factors for pulmonary embolism in women. J Am Med Assoc 1997; 277: 642-645.
  • 4 Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med 2005; 118: 978-980.
  • 5 Pomp ER, le Cessie S, Rosendaal FR. et al. Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Br J Haematol 2007; 139: 289-296.
  • 6 Allman-Farinelli MA. Obesity and venous thrombosis: a review. Semin Thromb Hemost 2011; 37: 903-907.
  • 7 Rocha AT, de Vasconcellos AG, da Luz Neto ER. et al. Risk of venous thromboembolism and efficacy of thromboprophylaxis in hospitalized obese medical patients and in obese patients undergoing bariatric surgery. Obes Surg 2006; 16: 1645-1655.
  • 8 Shibuya N, Frost CH, Campbell JD. et al. Incidence of acute deep vein thrombosis and pulmonary embolism in foot and ankle trauma: analysis of the National Trauma Data Bank. J Foot Ankle Surg 2012; 51: 63-68.
  • 9 Smith SB, Geske JB, Morgenthaler TI. Risk factors associated with delayed diagnosis of acute pulmonary embolism. J Emerg Med 2012; 42: 1-6.
  • 10 Tick LW, Kramer MH, Rosendaal FR. et al. Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis. J Thromb Haemost 2008; 6: 2075-2081.
  • 11 Blaszyk H, Bjornsson J. Factor V leiden and morbid obesity in fatal postoperative pulmonary embolism. Arch Surg 2000; 135: 1410-1413.
  • 12 Blaszyk H, Wollan PC, Witkiewicz AK. et al. Death from pulmonary throm-boembolism in severe obesity: lack of association with established genetic and clinical risk factors. Virchows Arch 1999; 434: 529-532.
  • 13 White RH, Gettner S, Newman JM. et al. Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med 2000; 343: 1758-1764.
  • 14 Raschke RA, Reilly BM, Guidry JR. et al. The weight-based heparin dosing no-mogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med 1993; 119: 874-881.
  • 15 Umscheid CA, Agarwal R, Gibson G. Weight-based low-molecular-weight he-parin versus weight-based intravenous unfractionated heparin. Ann Intern Med 2007; 147: 433-434 author reply 434
  • 16 Samama MM, Cohen AT, Darmon JY. et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999; 341: 793-800.
  • 17 Nutescu EA, Spinler SA, Wittkowsky A. et al. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 2009; 43: 1064-1083.
  • 18 Frederiksen SG, Hedenbro JL, Norgren L. Enoxaparin effect depends on body-weight and current doses may be inadequate in obese patients. Br J Surg 2003; 90: 547-548.
  • 19 Rowan BO, Kuhl DA, Lee MD. et al. Anti-Xa levels in bariatric surgery patients receiving prophylactic enoxaparin. Obes Surg 2008; 18: 162-166.
  • 20 Rondina MT, Wheeler M, Rodgers GM. et al. Weight-based dosing of enoxapa-rin for VTE prophylaxis in morbidly obese, medically-Ill patients. Thromb Res 2010; 125: 220-223.
  • 21 Freeman AL, Pendleton RC, Rondina MT. Prevention of venous thromboem-bolism in obesity. Expert Rev Cardiovasc Ther 2010; 8: 1711-1721.
  • 22 Freeman A, Horner T, Pendleton RC. et al. Prospective comparison of three en-oxaparin dosing regimens to achieve target anti-factor Xa levels in hospitalized, medically ill patients with extreme obesity. Am J Hematol 2012; 87: 740-743.
  • 23 Deal EN, Hollands JM, Reichley RM. et al. Characteristics of patients with morbid obesity at an academic medical center. Am J Health Syst Pharm 2010; 67: 1589-1590.
  • 24 Bakirhan K, Strakhan M. Pharmacologic prevention of venous thromboembol-ism in obese patients. J Thromb Thrombolysis 2013; 36: 247-257.
  • 25 White RH, Beyth RJ, Zhou H. et al. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999; 107: 414-424.
  • 26 Birman-Deych E, Waterman AD, Yan Y. et al. Accuracy of ICD-9-CM codes for identifying cardiovascular and stroke risk factors. Med Care 2005; 43: 480-485.
  • 27 Quan H, Sundararajan V, Halfon P. et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005; 43: 1130-1139.
  • 28 Turner K, Burchill C. This is the Charlson Comorbidity Index macro code using ICD-9-CM. Available at: . Accessed April 7, 2013.
  • 29 Badimon L, Hernandez Vera R, Padro T. et al. Antithrombotic therapy in obesity. Thromb Haemost 2013; 110: 681-688.
  • 30 Rosito GA, DAgostino RB, Massaro J. et al. Association between obesity and a prothrombotic state: the Framingham Offspring Study. Thromb Haemost 2004; 91: 683-689.
  • 31 Eichinger S, Hron G, Bialonczyk C. et al. Overweight, obesity, and the risk of recurrent venous thromboembolism. Arch Intern Med 2008; 168: 1678-1683.
  • 32 Darvall KA, Sam RC, Silverman SH. et al. Obesity and thrombosis. Eur J Vasc Endovasc Surg 2007; 33: 223-233.
  • 33 Ay L, Kopp HP, Brix JM. et al. Thrombin generation in morbid obesity: significant reduction after weight loss. J Thromb Haemost 2010; 8: 759-765.
  • 34 Semeraro F, Giordano P, Faienza MF. et al. Evidence that fibrinolytic changes in paediatric obesity translate into a hypofibrinolytic state: relative contribution of TAFI and PAI-1. Thromb Haemost 2012; 108: 311-317.
  • 35 Christiansen SC, Lijfering WM, Naess IA. et al. The relationship between body mass index, activated protein C resistance and risk of venous thrombosis. J Thromb Haemost 2012; 10: 1761-1767.
  • 36 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107: I4-8.
  • 37 Silverstein MD, Heit JA, Mohr DN. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
  • 38 Finks JF, English WJ, Carlin AM. et al. Predicting risk for venous thromboem-bolism with bariatric surgery: results from the Michigan Bariatric Surgery Collaborative. Ann Surg 2012; 255: 1100-1104.
  • 39 Imberti D, Bianchi C, Zambon A. et al. Venous thromboembolism after major orthopaedic surgery: a population-based cohort study. Intern Emerg Med 2012; 7: 243-249.
  • 40 Douketis J, Tosetto A, Marcucci M. et al. Risk of recurrence after venous throm-boembolism in men and women: patient level meta-analysis. Br Med J 2011; 342: d813
  • 41 Blom JW, Doggen CJ, Osanto S. et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. J Am Med Assoc 2005; 293: 715-722.
  • 42 Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012; 9: e1001275
  • 43 Anderson Jr. FA, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107 (23) (Suppl. 01) I9-16.
  • 44 Borkgren-Okonek MJ, Hart RW, Pantano JE. et al. Enoxaparin thromboprophy-laxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis 2008; 4: 625-631.
  • 45 Singh K, Podolsky ER, Um S. et al. Evaluating the safety and efficacy of BMI-based preoperative administration of low-molecular-weight heparin in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg 2012; 22: 47-51.
  • 46 Scholten DJ, Hoedema RM, Scholten SE. A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg 2002; 12: 19-24.
  • 47 Ludwig KP, Simons HJ, Mone M. et al. Implementation of an enoxaparin protocol for venous thromboembolism prophylaxis in obese surgical intensive care unit patients. Ann Pharmacother 2011; 45: 1356-1362.
  • 48 Kucher N, Koo S, Quiroz R. et al. Electronic alerts to prevent venous throm-boembolism among hospitalized patients. N Engl J Med 2005; 352: 969-977.
  • 49 Hijazi MH DT. Multidisciplinary approach improves compliance with venous thromboembolism prophylaxis. Chest 2009; 136: 150S