Ana Torres, Emanuele Chisari, Jessica Morton, Emilio Romanini, David Beverland, A. J. Andrade.
Response/Recommendation: Extensive evidence confirms a definite association between unprovoked venous thromboembolism (VTE) and increasing body mass index (BMI). However, the evidence linking BMI to postoperative VTE is more equivocal.
Strength of Recommendation: Moderate.
Rationale: VTE is a multifactorial disease, resulting from the interaction of genetic and acquired risk factors. Multiple observational population-based studies demonstrate that obesity, as assessed by increased BMI, is an independent risk factor for increased risk of VTE in the nonsurgical patient1–4. This association between BMI and VTE has been demonstrated to likely be causal in Mendelian randomization studies5,6. The World Health Organization (WHO) classifies BMI into underweight (BMI < 18.5 kg/m2), normal weight (BMI between 18.5 – 24.9 kg/m2), overweight (BMI between 25 – 29.9 kg/m2), Class 1 obese (BMI between 30 – 34.9 kg/m2), Class 2 obese (BMI between 35 – 39.9 kg/m2), and Class 3 obese (BMI ≥ 40 kg/m2)7. In clinical practice, obesity is typically defined as BMI > 30 kg/m2 8. With regards to orthopaedic surgery, conflicting evidence has been reported. The majority of studies have found that BMI > 30 kg/m2 correlates to a greater risk of VTE in both total hip arthroplasty (THA) and total knee arthroplasty (TKA)9–23. However, other studies have refuted these findings and have not detected and a correlation between high BMI and postoperative VTE24–29. In a systematic review and metanalysis, Zhang et al., found BMI > 30 kg/m2 to increase the risk of VTE in patients undergoing primary TKA and THA19. A larger metanalysis of 89 studies including 14’763,963 joint replacements found an increasing risk of VTE with increasing BMI, relative risks >25 kg/m2 vs < 25 kg/m2 1.40 (1.24-1.57), > 30 kg/m2 vs < 30 kg/m2 1.65 (1.23-2.22), and > 50 kg/m2 vs < 50 kg/m2 1.72 (1.10-2.67) . In analysis of the American College of Surgeons – National Surgical Quality Improvement Program (ACS-NSQIP) database, Sloan et al., found elevated BMI did not increase the risk of deep venous thrombosis (DVT) in revision TKA or THA, however, in patients undergoing primary THA and TKA elevated BMI was associated with elevated risk of pulmonary embolism (PE)9. In a single-institution study of 26,391 primary and revision TJA Parvizi et al., found that elevated BMI (p<0.035) was an independent risk factor for symptomatic PE12.
Obesity, as reflected in increased BMI, has not only been proven as a risk factor for VTE in THA and TKA but also in patients undergoing several other areas of orthopaedic surgery. In total shoulder arthroplasty obesity has been found to be a risk factor for VTE30,31. Obesity is also an independent risk factor for increased incidence of VTE after hip arthroscopy32,33, as well as shoulder and knee arthroscopy34. Obese patients have also found to be at an increased risk of VTE following foot and ankle surgery35–37. Although in patients with chronic Achilles tendon ruptures, elevated BMI trended towards association with VTE but did not reach statistical significance38. The literature in spine surgery generally continues to support BMI as a risk factor for VTE39–44, although there is not a universal consensus45,46. In patients who underwent lumbar spine surgery, the risk for DVT was higher in overweight patients and increased for subsequent obesity classes39. This is supported by metanalysis performed by Jiang et al., who noted odds ratio [OR] of 3.15 (95% confidence interval [CI] 1.92-5.17) for increased risk of VTE in obese patients, being defined as BMI > 30 kg/m2 40.
The exact etiology of a possible correlation between obesity and increased risk of VTE remains unknown. Obese patients may be at increased risk for VTE secondary to longer operative times, lower postoperative mobility, and ineffectiveness of mechanical prophylaxis9. Obesity has been associated with inflammatory states that may contribute to increased thrombus formation and subsequent embolization3,47. Furthermore, obesity is associated with reduced fibrinolysis attributable to increased concentrations of type-1 plasminogen activator inhibitor (PAI-1), an inhibitor of endogenous fibrinolysis, shifting the balance between thrombosis and thrombolysis towards thrombosis48.
The association between BMI and VTE remains unproven. Obese patients are also at higher risk of bleeding and wound-related complications. Thus, the use of any thromboprophylaxis should be balanced against the increased risk for complications and bleeding in obese patients9,49.
1. Borch KH, Braekkan SK, Mathiesen EB, et al. Anthropometric measures of obesity and risk of venous thromboembolism: the Tromso study. Arterioscler Thromb Vasc Biol. 2010;30(1):121-127. doi:10.1161/ATVBAHA.109.188920
2. Cushman M, O’Meara ES, Heckbert SR, Zakai NA, Rosamond W, Folsom AR. Body size measures, hemostatic and inflammatory markers and risk of venous thrombosis: The Longitudinal Investigation of Thromboembolism Etiology. Thromb Res. 2016;144:127-132. doi:10.1016/j.thromres.2016.06.012
3. Goldhaber SZ, Savage DD, Garrison RJ, et al. Risk factors for pulmonary embolism. The Framingham Study. Am J Med. 1983;74(6):1023-1028. doi:10.1016/0002-9343(83)90805-7
4. Glynn RJ, Rosner B. Comparison of risk factors for the competing risks of coronary heart disease, stroke, and venous thromboembolism. Am J Epidemiol. 2005;162(10):975-982. doi:10.1093/aje/kwi309
5. Klovaite J, Benn M, Nordestgaard BG. Obesity as a causal risk factor for deep venous thrombosis: a Mendelian randomization study. J Intern Med. 2015;277(5):573-584. doi:10.1111/joim.12299
6. Lindström S, Germain M, Crous-Bou M, et al. Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet. 2017;136(7):897-902. doi:10.1007/s00439-017-1811-x
7. Body mass index – BMI. Accessed September 16, 2021. https://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi
8. Obesity and overweight. Accessed September 16, 2021. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
9. Sloan M, Sheth N, Lee G-C. Is Obesity Associated With Increased Risk of Deep Vein Thrombosis or Pulmonary Embolism After Hip and Knee Arthroplasty? A Large Database Study. Clin Orthop. 2019;477(3):523-532. doi:10.1097/CORR.0000000000000615
10. George J, Piuzzi NS, Ng M, Sodhi N, Khlopas AA, Mont MA. Association Between Body Mass Index and Thirty-Day Complications After Total Knee Arthroplasty. J Arthroplasty. 2018;33(3):865-871. doi:10.1016/j.arth.2017.09.038
11. Kang J, Jiang X, Wu B. Analysis of Risk Factors for Lower-limb Deep Venous Thrombosis in Old Patients after Knee Arthroplasty. Chin Med J (Engl). 2015;128(10):1358-1362. doi:10.4103/0366-6999.156782
12. Parvizi J, Huang R, Raphael IJ, Arnold WV, Rothman RH. Symptomatic pulmonary embolus after joint arthroplasty: stratification of risk factors. Clin Orthop. 2014;472(3):903-912. doi:10.1007/s11999-013-3358-z
13. Wallace G, Judge A, Prieto-Alhambra D, de Vries F, Arden NK, Cooper C. The effect of body mass index on the risk of post-operative complications during the 6 months following total hip replacement or total knee replacement surgery. Osteoarthritis Cartilage. 2014;22(7):918-927. doi:10.1016/j.joca.2014.04.013
14. Mantilla CB, Horlocker TT, Schroeder DR, Berry DJ, Brown DL. Risk factors for clinically relevant pulmonary embolism and deep venous thrombosis in patients undergoing primary hip or knee arthroplasty. Anesthesiology. 2003;99(3):552-560; discussion 5A. doi:10.1097/00000542-200309000-00009
15. Haverkamp D, Klinkenbijl MN, Somford MP, Albers GHR, van der Vis HM. Obesity in total hip arthroplasty–does it really matter? A meta-analysis. Acta Orthop. 2011;82(4):417-422. doi:10.3109/17453674.2011.588859
16. Sun K, Li H. Body mass index as a predictor of outcome in total knee replace: A systemic review and meta-analysis. The Knee. 2017;24(5):917-924. doi:10.1016/j.knee.2017.05.022
17. Shaka H, Ojemolon PE. Impact of Obesity on Outcomes of Patients With Hip Osteoarthritis Who Underwent Hip Arthroplasty. Cureus. 2020;12(10):e10876. doi:10.7759/cureus.10876
18. Yukizawa Y, Inaba Y, Kobayashi N, Kubota S, Saito T. Current risk factors for asymptomatic venous thromboembolism in patients undergoing total hip arthroplasty. Mod Rheumatol. 2019;29(5):874-879. doi:10.1080/14397595.2018.1524959
19. Zhang J, Chen Z, Zheng J, Breusch SJ, Tian J. Risk factors for venous thromboembolism after total hip and total knee arthroplasty: a meta-analysis. Arch Orthop Trauma Surg. 2015;135(6):759-772. doi:10.1007/s00402-015-2208-8
20. Barrett MC, Whitehouse MR, Blom AW, Kunutsor SK. Host-related factors for venous thromboembolism following total joint replacement: A meta-analysis of 89 observational studies involving over 14 million hip and knee replacements. J Orthop Sci Off J Jpn Orthop Assoc. 2020;25(2):267-275. doi:10.1016/j.jos.2019.04.003
21. Song K, Rong Z, Yao Y, Shen Y, Zheng M, Jiang Q. Metabolic Syndrome and Deep Vein Thrombosis After Total Knee and Hip Arthroplasty. J Arthroplasty. 2016;31(6):1322-1325. doi:10.1016/j.arth.2015.12.021
22. Si H, Zeng Y, Shen B, et al. The influence of body mass index on the outcomes of primary total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2015;23(6):1824-1832. doi:10.1007/s00167-014-3301-1
23. White RH, Henderson MC. Risk factors for venous thromboembolism after total hip and knee replacement surgery. Curr Opin Pulm Med. 2002;8(5):365-371. doi:10.1097/00063198-200209000-00004
24. Petersen PB, Jørgensen CC, Kehlet H, Lundbeck Foundation Centre for Fast-track Hip Knee Replacement Collaborative Group. Venous Thromboembolism despite Ongoing Prophylaxis after Fast-Track Hip and Knee Arthroplasty: A Prospective Multicenter Study of 34,397 Procedures. Thromb Haemost. 2019;119(11):1877-1885. doi:10.1055/s-0039-1696686
25. Xu H, Zhang S, Xie J, et al. A nested case-control study on the risk factors of deep vein thrombosis for Chinese after total joint arthroplasty. J Orthop Surg. 2019;14(1):188. doi:10.1186/s13018-019-1231-9
26. Tay K, Bin Abd Razak HR, Tan AHC. Obesity and Venous Thromboembolism in Total Knee Arthroplasty Patients in an Asian Population. J Arthroplasty. 2016;31(12):2880-2883. doi:10.1016/j.arth.2016.05.061
27. Meller MM, Toossi N, Johanson NA, Gonzalez MH, Son M-S, Lau EC. Risk and Cost of 90-Day Complications in Morbidly and Superobese Patients After Total Knee Arthroplasty. J Arthroplasty. 2016;31(10):2091-2098. doi:10.1016/j.arth.2016.02.062
28. Kwasny MJ, Edelstein AI, Manning DW. Statistical Methods Dictate the Estimated Impact of Body Mass Index on Major and Minor Complications After Total Joint Arthroplasty. Clin Orthop. 2018;476(12):2418-2429. doi:10.1097/CORR.0000000000000493
29. Friedman RJ, Hess S, Berkowitz SD, Homering M. Complication rates after hip or knee arthroplasty in morbidly obese patients. Clin Orthop. 2013;471(10):3358-3366. doi:10.1007/s11999-013-3049-9
30. Tashjian RZ, Lilly DT, Isaacson AM, et al. Incidence of and Risk Factors for Symptomatic Venous Thromboembolism After Shoulder Arthroplasty. Am J Orthop Belle Mead NJ. 2016;45(6):E379-E385.
31. Young BL, Menendez ME, Baker DK, Ponce BA. Factors associated with in-hospital pulmonary embolism after shoulder arthroplasty. J Shoulder Elbow Surg. 2015;24(10):e271-278. doi:10.1016/j.jse.2015.04.002
32. Khazi ZM, An Q, Duchman KR, Westermann RW. Incidence and Risk Factors for Venous Thromboembolism Following Hip Arthroscopy: A Population-Based Study. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2019;35(8):2380-2384.e1. doi:10.1016/j.arthro.2019.03.054
33. Nicolay RW, Selley RS, Terry MA, Tjong VK. Body Mass Index as a Risk Factor for 30-Day Postoperative Complications in Knee, Hip, and Shoulder Arthroscopy. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2019;35(3):874-882.e3. doi:10.1016/j.arthro.2018.10.108
34. Collins JA, Beutel BG, Garofolo G, Youm T. Correlation of obesity with patient-reported outcomes and complications after hip arthroscopy. Arthrosc J Arthrosc Relat Surg Off Publ Arthrosc Assoc N Am Int Arthrosc Assoc. 2015;31(1):57-62. doi:10.1016/j.arthro.2014.07.013
35. Huntley SR, Abyar E, Lehtonen EJ, Patel HA, Naranje S, Shah A. Incidence of and Risk Factors for Venous Thromboembolism After Foot and Ankle Surgery. Foot Ankle Spec. 2019;12(3):218-227. doi:10.1177/1938640018769740
36. Richey JM, Ritterman Weintraub ML, Schuberth JM. Incidence and Risk Factors of Symptomatic Venous Thromboembolism Following Foot and Ankle Surgery. Foot Ankle Int. 2019;40(1):98-104. doi:10.1177/1071100718794851
37. Ahmad J, Lynch M-K, Maltenfort M. Incidence and Risk Factors of Venous Thromboembolism After Orthopaedic Foot and Ankle Surgery. Foot Ankle Spec. 2017;10(5):449-454. doi:10.1177/1938640017704944
38. Bullock MJ, DeCarbo WT, Hofbauer MH, Thun JD. Repair of Chronic Achilles Ruptures Has a High Incidence of Venous Thromboembolism. Foot Ankle Spec. 2017;10(5):415-420. doi:10.1177/1938640016679706
39. Marquez-Lara A, Nandyala SV, Sankaranarayanan S, Noureldin M, Singh K. Body mass index as a predictor of complications and mortality after lumbar spine surgery. Spine. 2014;39(10):798-804. doi:10.1097/BRS.0000000000000232
40. Jiang J, Teng Y, Fan Z, Khan S, Xia Y. Does obesity affect the surgical outcome and complication rates of spinal surgery? A meta-analysis. Clin Orthop. 2014;472(3):968-975. doi:10.1007/s11999-013-3346-3
41. Flippin M, Harris J, Paxton EW, et al. Effect of body mass index on patient outcomes of surgical intervention for the lumbar spine. J Spine Surg Hong Kong. 2017;3(3):349-357. doi:10.21037/jss.2017.06.15
42. Phan K, Kothari P, Lee NJ, Virk S, Kim JS, Cho SK. Impact of Obesity on Outcomes in Adults Undergoing Elective Posterior Cervical Fusion. Spine. 2017;42(4):261-266. doi:10.1097/BRS.0000000000001711
43. Buerba RA, Fu MC, Gruskay JA, Long WD, Grauer JN. Obese Class III patients at significantly greater risk of multiple complications after lumbar surgery: an analysis of 10,387 patients in the ACS NSQIP database. Spine J Off J North Am Spine Soc. 2014;14(9):2008-2018. doi:10.1016/j.spinee.2013.11.047
44. Patel N, Bagan B, Vadera S, et al. Obesity and spine surgery: relation to perioperative complications. J Neurosurg Spine. 2007;6(4):291-297. doi:10.3171/spi.2007.6.4.1
45. Cao J, Kong L, Meng F, Zhang Y, Shen Y. Impact of obesity on lumbar spinal surgery outcomes. J Clin Neurosci Off J Neurosurg Soc Australas. 2016;28:1-6. doi:10.1016/j.jocn.2015.10.034
46. Tan L, Qi B, Yu T, Wang C. Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis. Int Wound J. 2016;13(6):1359-1371. doi:10.1111/iwj.12533
47. Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med. 2005;118(9):978-980. doi:10.1016/j.amjmed.2005.03.012
48. Lundgren CH, Brown SL, Nordt TK, Sobel BE, Fujii S. Elaboration of type-1 plasminogen activator inhibitor from adipocytes. A potential pathogenetic link between obesity and cardiovascular disease. Circulation. 1996;93(1):106-110. doi:10.1161/01.cir.93.1.106
49. Parvizi J, Pour AE, Peak EL, Sharkey PF, Hozack WJ, Rothman RH. One-stage bilateral total hip arthroplasty compared with unilateral total hip arthroplasty: a prospective study. J Arthroplasty. 2006;21(6 Suppl 2):26-31. doi:10.1016/j.arth.2006.04.013