51 – Is there a correlation between age and the risk of VTE in patients undergoing orthopaedic procedures?

51 – Is there a correlation between age and the risk of VTE in patients undergoing orthopaedic procedures?

Karsten Keller, Lukas Hobohm.

Response/Recommendation: Increasing age is associated with an increased risk of postoperative venous thromboembolism (VTE) in patients undergoing orthopaedic procedures.

Strength of Recommendation: Strong.

Rationale: Increasing age is an important risk factor for the development of VTE1–9 as well as for a poor outcome following an acute VTE8,10–15.  The incidence of this complication has been shown to increase exponentially with age9,16 and this increase in risk is similar in both male and female individuals9.  Studies have revealed that the prevalence of established VTE risk factors also varies with age17.  In addition to major surgery, malignancy accounts for approximately 20% of the overall incidence of VTE18,19.  Familial and genetic factors are also important for the development of VTE, although the relative contribution of familial factors declines with age9.  Several epidemiologic studies have shown that the rate of VTE events following knee or hip joint replacements increases significantly with a patient’s age20–38.

The results of some key studies are presented as follows: White et al., demonstrated that patients‘ age was independently associated with a thromboembolic complication (odds ratio [OR] 1.15 for each 10-year increase in age over 50 years and a 95% confidence interval [CI], 1.1-1.3) among 19,586 patients who underwent primary hip arthroplasties and 24,059 who underwent primary knee arthroplasties24.  In a large nationwide study on hip replacements including 1’885,839 patients from 2005-2016 in Germany, Keller at al., reported that the number of VTE events increased with age (β 0.33 per age decade [95% CI 0.30-0.35])21.  A second study including 1’804,496 hospitalized patients who had elective primary knee joint replacement demonstrated that VTE risk was age-dependent (β 0.14 [95% CI 0.12 to 0.15], per age decade)22.  In accordance with these findings, in the Danish Knee Arthroplasty Registry, Pedersen et al., identified 37,223 primary knee arthroplasties performed from 1997 to 2007 in patients who received pharmacological thromboprophylaxis31.  The risk of hospitalization with VTE increased with increasing age, and this risk was highest in patients >80 years old (adjusted relative risk [RR] 1.58 [95% CI 1.01 to 2.47]) compared to patients <50 years31.  Yhim et al., analyzed 306,912 patients with total joint replacement (261,260 total knee and 45,652 total hip replacements) in the Health Insurance Review and Assessment Service (HIRA) database35.  Patients ≥60 years (OR 2.20 [95% CI 1.98–2.45]) showed a higher risk of postoperative VTE compared to patients <60 years35.  In the New York State database from 1985 to 2003, Lyman et al., analyzed 152,461 patients who had total hip arthroplasties (THA) and 162,085 who had total knee arthroplasty (TKA)38.  Increased age was associated with a higher number of VTE events (TKA: OR 1.03 per 10-year increase in age [95% CI 1.00-1.06]; THA: OR 1.10 per 10-year increase in age [95% CI 1.07-1.13])38.  In a separate study, Wu et al., analyzed 114,026 patients undergoing hip (n=61,460) or knee (n=52,566) replacement surgery between 2002 and 2006 using the National Health Insurance database of Taiwan and found that VTE rates in patients aged 60–69 (OR 2.33 [95% CI 1.34-4.06]) and 70–79 (OR 1.90 [95% CI 1.15-3.16]) years were higher compared to those who were younger than 50 years30.

In contrast, only a very few studies have reported no relationship between age and the incidence of VTE39–41.  Furthermore, others have reported divergent results for hip and knee arthroplasty32,34.  Data from the Spanish National Discharge Database in 2005–2006 revealed that age >70 years was associated with VTE in THA (OR 1.5 [95% CI 1.1–1.9]), but not associated with VTE in TKA33.  When analyzing 93,071 THA and 223,600 TKA in the Nationwide Inpatient Sample (NIS) database from 2003 to 2006, Kapoor et al., observed that age ≥80 years was accompanied by a higher postoperative VTE rate following THA compared to patients aged 65-69 years (OR 1.30 [95% CI 1.05-1.60]), but advanced age was not associated with a higher VTE rate in patients who underwent TKA32.

Although the rate of VTE after orthopedic surgeries of the upper limb is substantially lower than after orthopedic surgeries of the lower extremities42, an age-dependent increase was also found in most of these studies38,43–45.  In the study by Lyman et al., including 13,759 patients who underwent shoulder arthroplasty, an increase in VTE occurrence (OR 1.19 [95% CI 1.02-1.37]) was seen with every 10-year increase in age38.  Consistent with this, Kunutsor et al., conducted a large study of 672,495 primary shoulder and elbow replacements, observing that age ≥70 years was associated with an elevated risk for VTE (RR 1.15 [95% CI 1.08-1.22])43.  Jameson et al., similarly found an increased VTE risk after arthroscopy of the shoulder in 65,302 patients aged ≥70 years versus <60 years, but this association was not demonstrated in 10,229 patients undergoing elective shoulder replacement and 4,696 patients undergoing proximal humeral fracture surgery44.

The influence of age on VTE risk in patients with fractures of the lower extremity and oncologic orthopedic surgeries were not consistent46–55.  In patients undergoing surgical treatment of fractures below the hip, age ≥60 years was identified as a risk factor for VTE (RR 1.85 [95% CI 1.34-2.55]) in 191,294 patients46.  Similarly, Park et al., showed that advanced age of ≥60 years was associated with higher risk of VTE (OR 3.1 [1.3-7.4]) in 901 patients who underwent surgical treatment of fractures below the hip49.  In addition, Zhang et al., reported that patients ≥65 years of age had a higher risk of preoperative deep vein thrombosis following closed distal femur fractures (OR 4.39 [95% CI 1.73-11.16)56(p65).  In contrast, the study by McNamara et al., that analyzed 5,300 hip fracture patients revealed no age-dependent impact on VTE occurrence48.

A study by Congiusta et al., utilized the NIS database to determine the VTE rate after benign as well as malignant musculoskeletal tumor surgery55.  After analyzing more than 18,000 patients with benign tumors and more than 69,000 patients with malignant musculoskeletal tumors, all age groups except for patients ≥80 years had a higher frequency of VTE following malignant tumor surgery compared to the <30 years age group55.  In patients who had surgery for benign musculoskeletal tumors, only patients ≥80 years had a higher VTE risk55.  Fu et al., showed that in patients who had surgery for musculoskeletal tumors, an age of >60 years was associated with a higher VTE rate in comparison to patients aged <60 years (26.4% vs. 21.2%)47.  The study by Yamaguchi et al., identified age >70 years as a risk factor for VTE events in 94 patients undergoing musculoskeletal tumor resection52.  In contrast, other studies were not able to detect an association between age and VTE occurrence50,51,53,54.

In view of the wealth of national registry-based studies with large cohorts undergoing primary major joint replacements, fracture surgeries, and orthopedic tumor surgeries, there is ample evidence demonstrating an association between increasing age and a higher risk of VTE after orthopedic surgery20–36,38,43–46,49,55.  This association was stronger for patients who underwent THA20–36 compared to TKA32–34.  Although a patient’s age seems to be a weaker risk factor compared to other VTE risk factors (e.g., immobilization), it should be recognized that the prevalence of important concomitant VTE risk factors (e.g., malignancy) also increases with advanced age18,19,23,25,29,57.


1.         Stein PD, Hull RD, Kayali F, Ghali WA, Alshab AK, Olson RE. Venous thromboembolism according to age: the impact of an aging population. Arch Intern Med. 2004;164(20):2260-2265. doi:10.1001/archinte.164.20.2260

2.         Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost. 2000;83(5):657-660.

3.         Kyrle PA, Eichinger S. Deep vein thrombosis. The Lancet. 2005;365(9465):1163-1174. doi:10.1016/S0140-6736(05)71880-8

4.         Hippisley-Cox J, Coupland C. Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: prospective cohort study. BMJ. 2011;343:d4656. doi:10.1136/bmj.d4656

5.         Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998;158(6):585-593. doi:10.1001/archinte.158.6.585

6.         Kyrle PA, Minar E, Bialonczyk C, Hirschl M, Weltermann A, Eichinger S. The Risk of Recurrent Venous Thromboembolism in Men and Women. New England Journal of Medicine. 2004;350(25):2558-2563. doi:10.1056/NEJMoa032959

7.         Fimognari FL, Repetto L, Moro L, Gianni W, Incalzi RA. Age, cancer and the risk of venous thromboembolism. Crit Rev Oncol Hematol. 2005;55(3):207-212. doi:10.1016/j.critrevonc.2005.04.011

8.         Keller K, Hobohm L, Ebner M, et al. Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany. Eur Heart J. 2020;41(4):522-529. doi:10.1093/eurheartj/ehz236

9.         Zöller B, Li X, Sundquist J, Sundquist K. Age- and gender-specific familial risks for venous thromboembolism: a nationwide epidemiological study based on hospitalizations in Sweden. Circulation. 2011;124(9):1012-1020. doi:10.1161/CIRCULATIONAHA.110.965020

10.       Laporte S, Mismetti P, Décousus H, et al. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation. 2008;117(13):1711-1716. doi:10.1161/CIRCULATIONAHA.107.726232

11.       Grifoni S, Olivotto I, Cecchini P, et al. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation. 2000;101(24):2817-2822. doi:10.1161/01.cir.101.24.2817

12.       Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353(9162):1386-1389. doi:10.1016/s0140-6736(98)07534-5

13.       Uresandi F, Otero R, Cayuela A, et al. [A clinical prediction rule for identifying short-term risk of adverse events in patients with pulmonary thromboembolism]. Arch Bronconeumol. 2007;43(11):617-622. doi:10.1016/s1579-2129(07)60139-6

14.       Keller K, Beule J, Coldewey M, Dippold W, Balzer JO. Impact of advanced age on the severity of normotensive pulmonary embolism. Heart Vessels. 2015;30(5):647-656. doi:10.1007/s00380-014-0533-4

15.       Keller K, Beule J, Coldewey M, Geyer M, Balzer JO, Dippold W. The risk factor age in normotensive patients with pulmonary embolism: Effectiveness of age in predicting submassive pulmonary embolism, cardiac injury, right ventricular dysfunction and elevated systolic pulmonary artery pressure in normotensive pulmonary embolism patients. Exp Gerontol. 2015;69:116-121. doi:10.1016/j.exger.2015.05.007

16.       Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost. 2007;5(4):692-699. doi:10.1111/j.1538-7836.2007.02450.x

17.       Linnemann B, Weingarz L, Schindewolf M, et al. Prevalence of established risk factors for venous thromboembolism according to age. J Vasc Surg Venous Lymphat Disord. 2014;2(2):131-139. doi:10.1016/j.jvsv.2013.09.006

18.       Fernandes CJ, Morinaga LTK, Alves JL, et al. Cancer-associated thrombosis: the when, how and why. Eur Respir Rev. 2019;28(151):180119. doi:10.1183/16000617.0119-2018

19.       Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3-14. doi:10.1007/s11239-015-1311-6

20.       Baser O, Supina D, Sengupta N, Wang L, Kwong L. Impact of postoperative venous thromboembolism on Medicare recipients undergoing total hip replacement or total knee replacement surgery. Am J Health Syst Pharm. 2010;67(17):1438-1445. doi:10.2146/ajhp090572

21.       Keller K, Hobohm L, Barco S, et al. Venous thromboembolism in patients hospitalized for hip joint replacement surgery. Thromb Res. 2020;190:1-7. doi:10.1016/j.thromres.2020.03.019

22.       Keller K, Hobohm L, Barco S, et al. Venous thromboembolism in patients hospitalized for knee joint replacement surgery. Sci Rep. 2020;10(1):22440. doi:10.1038/s41598-020-79490-w

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.       White RH, Romano PS, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med. 1998;158(14):1525-1531. doi:10.1001/archinte.158.14.1525

25.       White RH, Gettner S, Newman JM, Trauner KB, Romano PS. Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med. 2000;343(24):1758-1764. doi:10.1056/NEJM200012143432403

26.       Samama C-M, Ravaud P, Parent F, Barré J, Mertl P, Mismetti P. Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study. J Thromb Haemost. 2007;5(12):2360-2367. doi:10.1111/j.1538-7836.2007.02779.x

27.       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

28.       White RH, Zhou H, Gage BF. Effect of age on the incidence of venous thromboembolism after major surgery. J Thromb Haemost. 2004;2(8):1327-1333. doi:10.1046/j.1538-7836.2004.00848.x

29.       Beksaç B, González Della Valle A, Salvati EA. Thromboembolic disease after total hip arthroplasty: who is at risk? Clin Orthop Relat Res. 2006;453:211-224. doi:10.1097/01.blo.0000238848.41670.41

30.       Wu P-K, Chen C-F, Chung L-H, Liu C-L, Chen W-M. Population-based epidemiology of postoperative venous thromboembolism in Taiwanese patients receiving hip or knee arthroplasty without pharmacological thromboprophylaxis. Thromb Res. 2014;133(5):719-724. doi:10.1016/j.thromres.2014.01.039

31.       Pedersen AB, Mehnert F, Johnsen SP, Husted S, Sorensen HT. Venous thromboembolism in patients having knee replacement and receiving thromboprophylaxis: a Danish population-based follow-up study. J Bone Joint Surg Am. 2011;93(14):1281-1287. doi:10.2106/JBJS.J.00676

32.       Kapoor A, Labonte AJ, Winter MR, et al. Risk of venous thromboembolism after total hip and knee replacement in older adults with comorbidity and co-occurring comorbidities in the Nationwide Inpatient Sample (2003-2006). BMC Geriatr. 2010;10:63. doi:10.1186/1471-2318-10-63

33.       Guijarro R, Montes J, San Román C, et al. Venous thromboembolism and bleeding after total knee and hip arthroplasty. Findings from the Spanish National Discharge Database. Thromb Haemost. 2011;105(4):610-615. doi:10.1160/TH10-10-0645

34.       Migita K, Bito S, Nakamura M, et al. Venous thromboembolism after total joint arthroplasty: results from a Japanese multicenter cohort study. Arthritis Res Ther. 2014;16(4):R154. doi:10.1186/ar4616

35.       Yhim H-Y, Lee J, Lee JY, Lee J-O, Bang S-M. Pharmacological thromboprophylaxis and its impact on venous thromboembolism following total knee and hip arthroplasty in Korea: A nationwide population-based study. PLoS One. 2017;12(5):e0178214. doi:10.1371/journal.pone.0178214

36.       Gade IL, Kold S, Severinsen MT, et al. Venous thromboembolism after lower extremity orthopedic surgery: A population-based nationwide cohort study. Res Pract Thromb Haemost. 2021;5(1):148-158. doi:10.1002/rth2.12449

37.       Parvizi J, Huang R, Rezapoor M, Bagheri B, Maltenfort MG. Individualized Risk Model for Venous Thromboembolism After Total Joint Arthroplasty. J Arthroplasty. 2016;31(9 Suppl):180-186. doi:10.1016/j.arth.2016.02.077

38.       Lyman S, Sherman S, Carter TI, Bach PB, Mandl LA, Marx RG. Prevalence and risk factors for symptomatic thromboembolic events after shoulder arthroplasty. Clin Orthop Relat Res. 2006;448:152-156. doi:10.1097/01.blo.0000194679.87258.6e

39.       Pedersen AB, Mehnert F, Sorensen HT, Emmeluth C, Overgaard S, Johnsen SP. The risk of venous thromboembolism, myocardial infarction, stroke, major bleeding and death in patients undergoing total hip and knee replacement: a 15-year retrospective cohort study of routine clinical practice. Bone Joint J. 2014;96-B(4):479-485. doi:10.1302/0301-620X.96B4.33209

40.       Jones CW, Parsons R, Yates PJ. Increased incidence of venous thromboembolism following hip or knee arthroplasty in winter. J Orthop Surg (Hong Kong). 2020;28(2):2309499020920749. doi:10.1177/2309499020920749

41.       Schiff RL, Kahn SR, Shrier I, et al. Identifying orthopedic patients at high risk for venous thromboembolism despite thromboprophylaxis. Chest. 2005;128(5):3364-3371. doi:10.1378/chest.128.5.3364

42.       Day JS, Ramsey ML, Lau E, Williams GR. Risk of venous thromboembolism after shoulder arthroplasty in the Medicare population. J Shoulder Elbow Surg. 2015;24(1):98-105. doi:10.1016/j.jse.2014.09.025

43.       Kunutsor SK, Barrett MC, Whitehouse MR, Blom AW. Venous thromboembolism following 672,495 primary total shoulder and elbow replacements: Meta-analyses of incidence, temporal trends and potential risk factors. Thromb Res. 2020;189:13-23. doi:10.1016/j.thromres.2020.02.018

44.       Jameson SS, James P, Howcroft DWJ, et al. Venous thromboembolic events are rare after shoulder surgery: analysis of a national database. J Shoulder Elbow Surg. 2011;20(5):764-770. doi:10.1016/j.jse.2010.11.034

45.       Willis AA, Warren RF, Craig EV, et al. Deep vein thrombosis after reconstructive shoulder arthroplasty: a prospective observational study. J Shoulder Elbow Surg. 2009;18(1):100-106. doi:10.1016/j.jse.2008.07.011

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.       Fu D, Zhao Y, Shen J, Cai Z, Hua Y. Comparison of Venous Thromboembolism after Total Artificial Joint Replacement between Musculoskeletal Tumors and Osteoarthritis of the Knee by a Single Surgeon. PLoS One. 2016;11(6):e0158215. doi:10.1371/journal.pone.0158215

48.       McNamara I, Sharma A, Prevost T, Parker M. Symptomatic venous thromboembolism following a hip fracture. Acta Orthop. 2009;80(6):687-692. doi:10.3109/17453670903448273

49.       Park S-J, Kim C-K, Park Y-S, Moon Y-W, Lim S-J, Kim S-M. Incidence and Factors Predicting Venous Thromboembolism After Surgical Treatment of Fractures Below the Hip. J Orthop Trauma. 2015;29(10):e349-354. doi:10.1097/BOT.0000000000000336

50.       Iwata S, Kawai A, Ueda T, Ishii T, Japanese Musculoskeletal Oncology Group (JMOG). Symptomatic Venous Thromboembolism in Patients with Malignant Bone and Soft Tissue Tumors: A Prospective Multicenter Cohort Study. Ann Surg Oncol. 2021;28(7):3919-3927. doi:10.1245/s10434-020-09308-6

51.       Lex JR, Evans S, Cool P, et al. Venous thromboembolism in orthopaedic oncology. Bone Joint J. 2020;102-B(12):1743-1751. doi:10.1302/0301-620X.102B12.BJJ-2019-1136.R3

52.       Yamaguchi T, Matsumine A, Niimi R, et al. Deep-vein thrombosis after resection of musculoskeletal tumours of the lower limb. Bone Joint J. 2013;95-B(9):1280-1284. doi:10.1302/0301-620X.95B9.30905

53.       Lin PP, Graham D, Hann LE, Boland PJ, Healey JH. Deep venous thrombosis after orthopedic surgery in adult cancer patients. J Surg Oncol. 1998;68(1):41-47. doi:10.1002/(sici)1096-9098(199805)68:1<41::aid-jso9>3.0.co;2-l

54.       Groot OQ, Ogink PT, Paulino Pereira NR, et al. High Risk of Symptomatic Venous Thromboembolism After Surgery for Spine Metastatic Bone Lesions: A Retrospective Study. Clin Orthop Relat Res. 2019;477(7):1674-1686. doi:10.1097/CORR.0000000000000733

55.       Congiusta DV, Amer KM, Thomson J, Ippolito J, Beebe KS, Benevenia J. Risk factors of venous thromboembolism in patients with benign and malignant musculoskeletal tumors: a dual database analysis. Int Orthop. 2020;44(10):2147-2153. doi:10.1007/s00264-020-04707-6

56.       Zhang J, Zhao K, Li J, Meng H, Zhu Y, Zhang Y. Age over 65 years and high levels of C-reactive protein are associated with the risk of preoperative deep vein thrombosis following closed distal femur fractures: a prospective cohort study. J Orthop Surg Res. 2020;15(1):559. doi:10.1186/s13018-020-02089-4

57.       Podmore B, Hutchings A, van der Meulen J, Aggarwal A, Konan S. Impact of comorbid conditions on outcomes of hip and knee replacement surgery: a systematic review and meta-analysis. BMJ Open. 2018;8(7):e021784. doi:10.1136/bmjopen-2018-021784

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