Jashvant Poeran, Panayiotis J. Papagelopoulos, Tanis Worthy, Michelle Ghert, M. Hardian Basuki, Felasfa Wodajo, Andreas Leithner.
Response/Recommendation: Patients undergoing surgical repairs of pathological fractures or those undergoing orthopaedic surgery with a history of malignancy or concurrent malignancy are at high risk for development of venous thromboembolism (VTE). While guidelines may provide some guidance in terms of choice of chemical agent and duration, the current evidence base is insufficient in determining optimal prophylaxis strategies, especially in light of factors that may further impact VTE risk in this high-risk population such as primary tumor site.
Strength of Recommendation: Limited.
Rationale: Major orthopaedic surgery, history of or concurrent malignancy, and major injury including fractures all represent independent risk factors for VTE1,2. For major elective orthopaedic surgery, VTE rates of >2%3,4 have been reported while this can be up to 15% or higher (depending on various factors such as concomitant treatment, age, and type of malignancy) for patients with a malignancy5 and 2-13% among patients with a pathological fracture6–9. It is unclear to what extent these independent risk factors represent a combined additive VTE risk in patients undergoing surgical repair of pathological fractures or other orthopaedic surgery with a history of malignancy or concurrent malignancy.
Given the co-existence of several individual risk factors, it is clear that this patient population should be considered at high risk of VTE10. However, arguably the most commonly cited VTE prophylaxis guideline specific to orthopaedic surgery, published by the American College of Chest Physicians (ACCP)4, does not provide clear guidance on prophylactic strategies for these patients. Moreover, while the American Academy of Orthopaedic Surgeons (AAOS) guideline includes studies that acknowledge cancer as a risk factor for VTE, it is solely focused on elective hip and knee arthroplasty surgery11. Some risk-stratified guidance does exist in the ACCP guideline for VTE prophylaxis in non-orthopaedic surgical patients12 recommending pharmacologic prophylaxis with low-molecular-weight heparin (LMWH), (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis with the suggested addition of mechanical prophylaxis with elastic stockings or intermittent pneumatic compression (Grade 2C) for patients at high risk for VTE but not at high risk for major bleeding complications. For high-risk patients undergoing abdominal or pelvic surgery for cancer, extended-duration postoperative, pharmacologic prophylaxis (4 weeks) is recommended (Grade 1B).
The preference for LMWH, extended duration of prophylaxis (up to 35 days) and concomitant use of intermittent pneumatic compression is reflected in the ACCP guideline for VTE prophylaxis in orthopaedic surgical patients, for those with the highest VTE risk4. This is also reflected in guidance from the United Kingdom’s National Institute for Health and Care Excellence (NICE) with a recommended duration of one month and the addition of fondaparinux as an option for highest-risk orthopaedic surgeries13.
Overall, the most common long-bone pathologic fractures include femur, tibia and humerus fractures14. The sparse literature focusing on VTE and prophylaxis in this specific patient population includes only a handful of observational studies6,7,15, almost none including a comparison between chemical prophylaxis strategies. For example, Shallop et al., retrospectively reviewed VTE rates and prophylaxis among 287 patients with impending or pathologic long-bone fractures stabilized with intramedullary nailing15. They found that LMWH (60.4% of cases) and warfarin (16.7% of cases) were the most commonly used chemical agents and protocols in all included centers directed chemical VTE prophylaxis for two weeks postoperatively. Importantly, the type of anticoagulant used was not associated with development of VTE, suggesting either a likely underpowered study (given the low number of VTE events) or the limited utility of the utilized chemical prophylaxis strategies to impact VTE risk in this high-risk population15. There was also no relationship between VTE prophylaxis and wound complications15. One factor that did impact VTE risk was primary histology, with higher VTE risks seen in patients with a primary tumor of the lung15.
Similarly, in a cohort of 85 lower limb pathologic fractures, Mioc et al., found LMWH to be the most commonly used prophylactic agent, and no association between type of agent and deep venous thrombosis (DVT) (pulmonary embolism [PE] was not considered), further suggesting that “a more aggressive prophylactic protocol should be used” in these patients6.
In conclusion, while it is clear that patients with a (history of) malignancy undergoing orthopaedic surgery, or specifically, surgical repair of a pathological fracture, are at high risk for VTE, the current evidence base does not support a clear VTE prophylaxis strategy. Evidence-based guidance is lacking on the type of agent, duration of prophylaxis, and how to modify options based on additional risk factors such as site of primary tumor. There is some guidance from current guidelines, however, prospective comparative studies are needed to refine recommendations.
1. White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost. 2003;90(3):446-455. doi:10.1160/TH03-03-0152
2. Anderson FA, Spencer FA. Risk Factors for Venous Thromboembolism. Circulation. 2003;107(23_suppl_1):I-9. doi:10.1161/01.CIR.0000078469.07362.E6
3. Farfan M, Bautista M, Bonilla G, Rojas J, Llinás A, Navas J. Worldwide adherence to ACCP guidelines for thromboprophylaxis after major orthopedic surgery: A systematic review of the literature and meta-analysis. Thromb Res. 2016;141:163-170. doi:10.1016/j.thromres.2016.03.029
4. 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
5. Khan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. The Lancet. 2021;398(10294):64-77. doi:10.1016/S0140-6736(20)32658-1
6. Mioc M-L, Prejbeanu R, Vermesan D, et al. Deep vein thrombosis following the treatment of lower limb pathologic bone fractures – a comparative study. BMC Musculoskelet Disord. 2018;19(1):213. doi:10.1186/s12891-018-2141-4
7. Aneja A, Jiang JJ, Cohen-Rosenblum A, et al. Thromboembolic Disease in Patients with Metastatic Femoral Lesions: A Comparison Between Prophylactic Fixation and Fracture Fixation. J Bone Joint Surg Am. 2017;99(4):315-323. doi:10.2106/JBJS.16.00023
8. Janssen SJ, Kortlever JTP, Ready JE, et al. Complications After Surgical Management of Proximal Femoral Metastasis: A Retrospective Study of 417 Patients. J Am Acad Orthop Surg. 2016;24(7):483-494. doi:10.5435/JAAOS-D-16-00043
9. Park KJ, Menendez ME, Mears SC, Barnes CL. Patients With Multiple Myeloma Have More Complications After Surgical Treatment of Hip Fracture. Geriatr Orthop Surg Rehabil. 2016;7(3):158-162. doi:10.1177/2151458516658330
10. Bartlett MA, Mauck KF, Stephenson CR, Ganesh R, Daniels PR. Perioperative Venous Thromboembolism Prophylaxis. Mayo Clinic Proceedings. 2020;95(12):2775-2798. doi:10.1016/j.mayocp.2020.06.015
11. Jacobs JJ, Mont MA, Bozic KJ, et al. American Academy of Orthopaedic Surgeons clinical practice guideline on: preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Bone Joint Surg Am. 2012;94(8):746-747. doi:10.2106/JBJS.9408.ebo746
12. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e227S-e277S. doi:10.1378/chest.11-2297
13. Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. pulmonary embolism. Published online 2019:44.
14. Hu Y-C, Lun D-X, Wang H. Clinical features of neoplastic pathological fracture in long bones. Chin Med J (Engl). 2012;125(17):3127-3132.
15. Shallop B, Starks A, Greenbaum S, et al. Thromboembolism After Intramedullary Nailing for Metastatic Bone Lesions. J Bone Joint Surg Am. 2015;97(18):1503-1511. doi:10.2106/JBJS.N.01067