189 – What is the most optimal VTE prophylaxis for patients undergoing internal fixation of a hip fracture?

189 – What is the most optimal VTE prophylaxis for patients undergoing internal fixation of a hip fracture?

Andrew J. Hughes, Jayaramaraju Dheenadhayalan, Svetlana Bozhkova, Aleksandar Lesic, Nagashree Vasudeva, Alina Kasimova, Punaganapathi Sundaram Velmurugesan, Jamino Ahn, Chad A. Krueger.

Response/Recommendation: Mechanical and pharmacological venous thromboembolism (VTE) prophylaxes are advised for patients undergoing internal fixation of a hip fracture, following an individualized risk assessment. In the setting of surgical delays, preoperative pharmacological prophylaxis should be considered. Pharmacological thromboprophylaxis should continue throughout the persistent postoperative prothrombotic state, commencing 12 hours post wound closure, and continuing for at least 28 days.

Strength of Recommendation: Moderate

Rationale: Patients sustaining hip fracture are subjected to a risk of VTE quoted at over 30% within the literature1–4. Advancements in thromboprophylaxis have reduced the overall rates of clinically relevant VTE to less than 4%5–8. The goals of VTE prophylaxis within this at-risk cohort are to prevent fatal pulmonary embolism (PE) and reduce the incidence of post-VTE morbidity, both of which contribute to the significant in-hospital and one-year mortality rates9–11. Despite widespread awareness of the merits of thromboprophylaxis, variability in practice patterns persist, owing to a lack of available high-quality evidence12–15. As such, published clinical practice guidelines (CPG) have made efforts to highlight the standards required of healthcare providers so as to mitigate VTE risk within the hip fracture population6,15–18.

On admission, it is advised that hip fracture patients undergo medical optimization, adequate hydration and receive mechanical prophylaxis, using graduated compression stockings (GCS) or intermittent pneumatic compression devices (IPCD), ensuring correct application, provided no contraindications are identified6,16,17,19,20. Pharmacological prophylaxis should be considered preoperatively if surgical delays are anticipated, commenced ideally within 14 hours of admission, following a comprehensive bleeding and thrombosis risk assessment21. Appropriate preoperative agents include either low-molecular-weight heparin (LMWH), with the last dose administered no less than 12 hours preoperatively, or unfractionated heparin (UFH) with close serological monitoring, particularly in patients requiring weight or renal adjusted formulations16,21,22. Fondaparinux use has been historically suggested, however its use has been more recently cautioned preoperatively given its known protracted onset of action, and the need for 24 hours to ensure adequate pharmacological clearance. In addition to mechanical and chemical thromboprophylaxis, early definitive internal fixation is favored, so as to mitigate the crescendo effect of delayed surgical intervention on VTE risk, whilst also minimizing the period of preoperative bed-rest5,23,24.

Postoperatively, mechanical prophylaxis should take the form of early mobilization, coupled with continuous GCS or IPCD use for the duration of stay in both the acute hospital and post-discharge rehabilitation settings18,19,25,26. Choice of GCS length, either knee-length or thigh-length, should rely on patient compliance, preference, and local skin condition, as no significant difference has been identified to date between either in preventing postoperative VTE27. Mechanical prophylaxis has also been advised to continue, for at least 18 hours per day, until a level of mobility is achieved resembling the patient’s pre-admission status16,19,20.

The published CPG all agree that pharmacological prophylaxis, in combination with mechanical prophylaxis, is required to prevent fatal PE and post-VTE morbidity. Postoperatively, it is suggested that the first prophylactic dose should be administered no sooner than 12 hours post wound closure16,18,28,29. Agents proven to be efficacious in the setting of hip fractures include LMWH, UFH, fondaparinux, adjusted-dose vitamin K antagonists and aspirin (ASA)6. Agent selection should be based on patient parameters, healthcare provider preferences and a shared decision. Therapy should continue for a minimum of 10 to 14 days, with most recommendations within CPG to continue for at least 28 to 35 days postoperatively, in light of the persistently elevated postoperative VTE risk4,7,16,18,28,30,31. LMWH or UFH are often utilized in the early postoperative period in clinical practice, given their parenteral preparations and reliable pharmacokinetics5.

To date, a leading pharmacological agent has yet to be defined. LMWH has been established as the prophylactic agent against which novel medications are compared6. The American College of Chest Physicians (ACCP), and the American Society of Hematology (ASH) guidelines both specifically advocate for a full extended prophylactic course of LMWH in the setting of a hip fracture, despite surgeon reservations surrounding the need for administration education, as well as the inconvenience of daily subcutaneous injections6,18. Fondaparinux has demonstrated equivocal VTE rates to LMWH but has been cautioned in light of major bleeding rates experienced by frail patients weighing less than 50 kilograms6,32. Warfarin, a vitamin K antagonist, has not demonstrated significant benefits compared to LMWH in the hip fracture population to date. Safety concerns with warfarin remain, particularly in relation to management of the international normalized ratio (INR) perioperatively, contributions to surgical delays due to prolonged clearance, slow-onset on action, and drug interactions affecting its efficacy5,6,29,33,34. Rivaroxaban, dabigatran, and apixaban have been approved for use against VTE in the setting of total joint arthroplasty but have not yet been sufficiently evaluated in the setting of hip fractures. Recent studies, one of retrospective nature, and one randomized controlled trial with small sample sizes in all study groups, demonstrated encouraging results with direct oral anticoagulant (DOAC) use, however further evidence is required before clinical practice is influenced35,36. ASA has been shown to significantly reduce VTE rates throughout the high-risk post-fracture time period compared to placebo, but routine ASA use remains controversial, given the lack of evidence to support equivalence to LMWH proven efficacy37,38. ASA and DOAC use have come under investigation of late. Two heterogenous meta-analyses, recently published, suggest favorable findings with regards to VTE reduction, however level one evidence is yet to emerge39,40. Both agents are convenient given their more simplistic oral regimens and encouragingly low rates of VTE, but reservations persist concerning hemorrhagic events, particularly in the immediate postoperative period34,41.

A clear consensus amongst CPG is unfortunately lacking regarding the optimal pharmacological agent, dose, and duration. Concerns surround balancing the susceptibility of hip fracture patients to VTE, with the rate of wound complications and significant hemorrhagic events42. Despite recent advancements in enhanced recovery programs, clinical care pathways, and national audit programs, which have combined to improve the standard of hip fracture care worldwide, VTE CPG continue to reference evidence stemming from the 1990’s and 2000’s. As such, focusing future research efforts on well-designed high-quality trials is of utmost importance, so as to clarify a consensus on means to reliably prevent VTE in the hip fracture population, and facilitate the publication of guidelines that will positively influence clinical practice.


1.         Pedersen AB, Ehrenstein V, Szépligeti SK, Sørensen HT. Excess risk of venous thromboembolism in hip fracture patients and the prognostic impact of comorbidity. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2017;28(12):3421-3430. doi:10.1007/s00198-017-4213-y

2.         Nakase J, Toribatake Y, Mouri Y, Seki H, Kitaoka K, Tomita K. Heparin versus danaproid for prevention of venous thromboembolism after hip surgery. J Orthop Surg Hong Kong. 2009;17(1):6-9. doi:10.1177/230949900901700102

3.         Eriksson BI, Lassen MR, PENTasaccharide in HIp-FRActure Surgery Plus Investigators. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2003;163(11):1337-1342. doi:10.1001/archinte.163.11.1337

4.         Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):338S-400S. doi:10.1378/chest.126.3_suppl.338S

5.         Ricci WM, Broekhuyse H, Keating JF, Teague DC, White TO. Thromboprophylaxis an update of current practice: Can we reach a consensus? OTA Int Open Access J Orthop Trauma. 2019;2(4):e027. doi:10.1097/OI9.0000000000000027

6.         Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e278S-e325S. doi:10.1378/chest.11-2404

7.         Rosencher N, Vielpeau C, Emmerich J, Fagnani F, Samama CM, ESCORTE group. Venous thromboembolism and mortality after hip fracture surgery: the ESCORTE study. J Thromb Haemost JTH. 2005;3(9):2006-2014. doi:10.1111/j.1538-7836.2005.01545.x

8.         MacDonald DRW, Neilly D, Schneider PS, et al. Venous Thromboembolism in Hip Fracture Patients: A Subanalysis of the FAITH and HEALTH Trials. J Orthop Trauma. 2020;34 Suppl 3:S70-S75. doi:10.1097/BOT.0000000000001939

9.         Nicholson M, Chan N, Bhagirath V, Ginsberg J. Prevention of Venous Thromboembolism in 2020 and Beyond. J Clin Med. 2020;9(8):E2467. doi:10.3390/jcm9082467

10.       Downey C, Kelly M, Quinlan JF. Changing trends in the mortality rate at 1-year post hip fracture – a systematic review. World J Orthop. 2019;10(3):166-175. doi:10.5312/wjo.v10.i3.166

11.       Lawrence VA, Hilsenbeck SG, Noveck H, Poses RM, Carson JL. Medical complications and outcomes after hip fracture repair. Arch Intern Med. 2002;162(18):2053-2057. doi:10.1001/archinte.162.18.2053

12.       Sagi HC, Ahn J, Ciesla D, et al. Venous Thromboembolism Prophylaxis in Orthopaedic Trauma Patients: A Survey of OTA Member Practice Patterns and OTA Expert Panel Recommendations. J Orthop Trauma. 2015;29(10):e355-362. doi:10.1097/BOT.0000000000000387

13.       Handoll HH, Farrar MJ, McBirnie J, Tytherleigh-Strong G, Milne AA, Gillespie WJ. Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures. Cochrane Database Syst Rev. 2002;(4):CD000305. doi:10.1002/14651858.CD000305

14.       Alsawadi A, Loeffler M. Graduated compression stockings in hip fractures. Ann R Coll Surg Engl. 2012;94(7):463-471. doi:10.1308/003588412X13171221592492

15.       Scottish Intercollegiate Guidelines Network. Management of Hip Fracture in Older People: A National Clinical Guideline. Scottish Intercollegiate Guidelines Network; 2009.

16.       Overview | Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism | Guidance | NICE. Accessed October 21, 2021. https://www.nice.org.uk/guidance/NG89

17.       hip-fractures-elderly-clinical-practice-guideline-4-24-19–2.pdf. Accessed October 21, 2021. https://www.aaos.org/globalassets/quality-and-practice-resources/hip-fractures-in-the-elderly/hip-fractures-elderly-clinical-practice-guideline-4-24-19–2.pdf

18.       Anderson DR, Morgano GP, Bennett C, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019;3(23):3898-3944. doi:10.1182/bloodadvances.2019000975

19.       Amarase C, Tanavalee A, Larbpaiboonpong V, et al. Asia-Pacific venous thromboembolism consensus in knee and hip arthroplasty and hip fracture surgery: Part 2. Mechanical venous thromboembolism prophylaxis. Knee Surg Relat Res. 2021;33(1):20. doi:10.1186/s43019-021-00101-7

20.       Mehta KV, Lee HC, Loh JSY. Mechanical thromboprophylaxis for patients undergoing hip fracture surgery. J Orthop Surg Hong Kong. 2010;18(3):287-289. doi:10.1177/230949901001800306

21.       Perioperative care overview – NICE Pathways. Accessed October 1, 2021. https://pathways.nice.org.uk/pathways/perioperative-care

22.       Overview | Venous thromboembolism in adults | Quality standards | NICE. Accessed October 21, 2021. https://www.nice.org.uk/guidance/qs201

23.       Smith EB, Parvizi J, Purtill JJ. Delayed surgery for patients with femur and hip fractures-risk of deep venous thrombosis. J Trauma. 2011;70(6):E113-116. doi:10.1097/TA.0b013e31821b8768

24.       Hughes AJ, Brent L, Biesma R, Kenny PJ, Hurson CJ. The effect of indirect admission via hospital transfer on hip fracture patients in Ireland. Ir J Med Sci. 2019;188(2):517-524. doi:10.1007/s11845-018-1854-6

25.       Pavon JM, Adam SS, Razouki ZA, et al. Effectiveness of Intermittent Pneumatic Compression Devices for Venous Thromboembolism Prophylaxis in High-Risk Surgical Patients: A Systematic Review. J Arthroplasty. 2016;31(2):524-532. doi:10.1016/j.arth.2015.09.043

26.       Gill SK, Pearce AR, Everington T, Rossiter ND. Mechanical prophylaxis, early mobilisation and risk stratification: as effective as drugs for low risk patients undergoing primary joint replacement. Results in 13,384 patients. Surg J R Coll Surg Edinb Irel. 2020;18(4):219-225. doi:10.1016/j.surge.2019.11.002

27.       Sajid MS, Desai M, Morris RW, Hamilton G. Knee length versus thigh length graduated compression stockings for prevention of deep vein thrombosis in postoperative surgical patients. Cochrane Database Syst Rev. 2012;(5):CD007162. doi:10.1002/14651858.CD007162.pub2

28.       Clinical Guides. Thrombosis Canada – Thrombose Canada. Published April 8, 2013. Accessed October 21, 2021. https://thrombosiscanada.ca/clinicalguides/

29.       Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e326S-e350S. doi:10.1378/chest.11-2298

30.       Fisher WD, Agnelli G, George DJ, et al. Extended venous thromboembolism prophylaxis in patients undergoing hip fracture surgery – the SAVE-HIP3 study. Bone Jt J. 2013;95-B(4):459-466. doi:10.1302/0301-620X.95B4.30730

31.       Bjørnarå BT, Gudmundsen TE, Dahl OE. Frequency and timing of clinical venous thromboembolism after major joint surgery. J Bone Joint Surg Br. 2006;88(3):386-391. doi:10.1302/0301-620X.88B3.17207

32.       Eriksson BI, Bauer KA, Lassen MR, Turpie AG, Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001;345(18):1298-1304. doi:10.1056/NEJMoa011100

33.       Mismetti P, Laporte S, Zufferey P, Epinat M, Decousus H, Cucherat M. Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis. J Thromb Haemost JTH. 2004;2(7):1058-1070. doi:10.1111/j.1538-7836.2004.00757.x

34.       Thiengwittayaporn S, Budhiparama N, Tanavalee C, et al. Asia-Pacific venous thromboembolism consensus in knee and hip arthroplasty and hip fracture surgery: Part 3. Pharmacological venous thromboembolism prophylaxis. Knee Surg Relat Res. 2021;33(1):24. doi:10.1186/s43019-021-00100-8

35.       Goh EL, Gurung PK, Ma S, et al. Direct Oral Anticoagulants in the Prevention of Venous Thromboembolism Following Surgery for Hip Fracture in Older Adults: A Population-Based Cohort Study. Geriatr Orthop Surg Rehabil. 2020;11:2151459319897520. doi:10.1177/2151459319897520

36.       Tang Y, Wang K, Shi Z, Yang P, Dang X. A RCT study of Rivaroxaban, low-molecular-weight heparin, and sequential medication regimens for the prevention of venous thrombosis after internal fixation of hip fracture. Biomed Pharmacother Biomedecine Pharmacother. 2017;92:982-988. doi:10.1016/j.biopha.2017.05.107

37.       Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet Lond Engl. 2000;355(9212):1295-1302.

38.       Huang Q, Xing S-X, Zeng Y, Si H-B, Zhou Z-K, Shen B. Comparison of the Efficacy and Safety of Aspirin and Rivaroxaban Following Enoxaparin Treatment for Prevention of Venous Thromboembolism after Hip Fracture Surgery. Orthop Surg. 2019;11(5):886-894. doi:10.1111/os.12542

39.       Wæver D, Lewis D, Saksø H, Borris LC, Tarrant S, Thorninger R. The Effectiveness and Safety of Direct Oral Anticoagulants Following Lower Limb Fracture Surgery: A Systematic Review and Meta-analysis. J Orthop Trauma. 2021;35(4):217-224. doi:10.1097/BOT.0000000000001962

40.       Hu B, Jiang L, Tang H, Hu M, Yu J, Dai Z. Rivaroxaban versus aspirin in prevention of venous thromboembolism following total joint arthroplasty or hip fracture surgery: a meta-analysis. J Orthop Surg. 2021;16(1):135. doi:10.1186/s13018-021-02274-z

41.       Flevas DA, Megaloikonomos PD, Dimopoulos L, Mitsiokapa E, Koulouvaris P, Mavrogenis AF. Thromboembolism prophylaxis in orthopaedics: an update. EFORT Open Rev. 2018;3(4):136-148. doi:10.1302/2058-5241.3.170018

42.       Muscatelli SR, Charters MA, Hallstrom BR. Time for an Update? A Look at Current Guidelines for Venous Thromboembolism Prophylaxis After Hip and Knee Arthroplasty and Hip Fracture. Arthroplasty Today. 2021;10:105-107. doi:10.1016/j.artd.2021.06.015

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