Abdulaziz Aljurayyan, Ahmed Alabdali, Ryan K Harrison.
Response/Recommendation: Although multiple forms of prophylaxis against venous thromboembolism (VTE) with variable effectiveness are available for patients with multiple orthopedic injuries, low-molecular-weight heparin (LMWH) is considered the most optimal choice based on available literature.
Strength of Recommendation: Acceptable.
Rationale: VTE events following multiple orthopaedic injuries are associated with significant morbidity and mortality1,2. The prevalence of deep venous thrombosis (DVT) in trauma patients without prophylactic treatment can reach up to 60%. Pulmonary embolism (PE) can be a fatal form of VTE with prevalence ranging between 2-16%3,4. VTE can be prevented using different mechanical and chemical prophylaxis agents, therefore, significantly lower the burden on healthcare systems worldwide1. The aim of this review is to find the most optimal VTE prophylaxis in patients with multiple orthopaedic injuries.
Multiple orthopaedic injuries rarely happen without extra-skeletal injuries, therefore, no studies in the current literature addressed VTE prophylaxis in patients with multiple orthopaedic injuries but without extra-skeletal injuries. Most of the available literature is addressing this patient population under different groups including, patients with trauma, poly-trauma, high energy fractures, and lower extremity injuries1–3,5–7. The level of evidence varies among the reviewed literature, however, randomized controlled clinical trials in this subject are limited3,4.
Based on our review, LMWH is considered the most optimal VTE prophylaxis in patients with multiple orthopaedic injuries1,3,5,6,8–14. Ley et al., recommends using LMWH due to its increased bioavailability, acceptably low bleeding complications and longer plasma half-life1. Rogers et al., published in their guidelines for prevention of VTE in trauma patients that LMWH has superior bioavailability when compared to low dose heparin (LDH)5. Knudson et al., concluded in a prospective, randomized trial that LMWH is an extremely effective and safe method in preventing DVT in high-risk trauma patients15. Geerts et al., also concluded in a randomized double-blinded study that LMWH was more effective than LDH in preventing VTE after major trauma16. Aggarwal et al., concluded in their guidelines for prevention of VTE in hospitalized patients with pelvis and acetabular fractures that LMWH is the preferred agent of choice8.
In the updated Western Trauma Association (WTA) guidelines to reduce VTE in trauma patients1, LMWH was the recommended agent of choice for most trauma patients with a standard dose of 40 mg subcutaneously twice daily. However, in some cases such as obese patients, they recommended weight-based dosing at 0.5 mg to 0.6 mg/kg twice daily1. Timing of administration of LMWH is critical to achieve the optimal prophylaxis desired. It should be given to patients as soon as risk of bleeding is low to avoid complications1,3,11,17. According to Ley et al., pharmacologic prophylaxis should be started as soon as possible within 24 hours after injury1.
Fondaparinux18 is a synthetic penta-saccharide drug that potentiates activity of antithrombin III that inhibits factor Xa. With a common dosage of 2.5 mg daily subcutaneously, this chemical prophylaxis showed promising results in elective orthopaedic surgery such as arthroplasty19. However, several issues have been raised to debate its safety in trauma patients18,20. Therefore, further studies are required to prove its safety and efficacy in trauma5.
Another method of prophylaxis is the use of mechanical prophylaxis in form of pneumatic compression devices (PCD) which was promoted by the Eastern Association for the Surgery of Trauma (EAST) workgroup practice management guidelines for the prevention of VTE in trauma patients3, especially in patients where chemical prophylaxis is contraindicated1,6–8,21. PCD can be used as an adjunct with chemical prophylaxis in moderate and high-risk patients1,10,22,23. The combination has shown lower incidence of symptomatic PE according to Ley et al1. High-risk patients include those with hemodynamic instability, active bleeding, and head trauma1,5,8. The use of mechanical prophylaxis without chemical prophylaxis in the absence of contraindication to chemical prophylaxis is not recommended according to multiple studies2,7.
Inferior vena cava (IVC) filters are another form of prophylaxis against VTE4,24, although they are not without risk. It has an established role as an adjunct to LMWH in patients with DVT to prevent PE8. However, multiple studies recommend the use of IVC filters to be reserved for patients who cannot receive any form of prophylaxis or patients undergoing urgent surgery5,6,25. Khansarinia et al., concluded that insertion of IVC filter in multiply injured high-risk patients contributed to lower incidence and mortality rates of fatal and non-fatal PE24.
1. Ley EJ, Brown CVR, Moore EE, et al. Updated guidelines to reduce venous thromboembolism in trauma patients: A Western Trauma Association critical decisions algorithm. J Trauma Acute Care Surg. 2020;89(5):971-981. doi:10.1097/TA.0000000000002830
2. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):381S-453S. doi:10.1378/chest.08-0656
3. Toker S, Hak DJ, Morgan SJ. Deep vein thrombosis prophylaxis in trauma patients. Thrombosis. 2011;2011:505373. doi:10.1155/2011/505373
4. Slobogean GP, Lefaivre KA, Nicolaou S, O’Brien PJ. A systematic review of thromboprophylaxis for pelvic and acetabular fractures. J Orthop Trauma. 2009;23(5):379-384. doi:10.1097/BOT.0b013e3181a5369c
5. Rogers FB, Cipolle MD, Velmahos G, Rozycki G, Luchette FA. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: the EAST practice management guidelines work group. J Trauma. 2002;53(1):142-164. doi:10.1097/00005373-200207000-00032
6. Chana-Rodríguez F, Mañanes RP, Rojo-Manaute J, Haro JAC, Vaquero-Martín J. Methods and Guidelines for Venous Thromboembolism Prevention in Polytrauma Patients with Pelvic and Acetabular Fractures. Open Orthop J. 2015;9:313-320. doi:10.2174/1874325001509010313
7. Niikura T, Sakai Y, Lee SY, Iwakura T, Kuroda R, Kurosaka M. Rate of venous thromboembolism after complex lower-limb fracture surgery without pharmacological prophylaxis. J Orthop Surg Hong Kong. 2015;23(1):37-40. doi:10.1177/230949901502300109
8. Aggarwal S, Patel S, Vashisht S, et al. Guidelines for the prevention of venous thromboembolism in hospitalized patients with pelvi-acetabular trauma. J Clin Orthop Trauma. 2020;11(6):1002-1008. doi:10.1016/j.jcot.2020.09.011
9. Wang H, Chen W, Su Y, et al. Thrombotic risk assessment questionary helps increase the use of thromboprophylaxis for patients with pelvic and acetabular fractures. Indian J Orthop. 2012;46(4):413-419. doi:10.4103/0019-5413.98830
10. 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
11. Jehan F, O’Keeffe T, Khan M, et al. Early thromboprophylaxis with low-molecular-weight heparin is safe in patients with pelvic fracture managed nonoperatively. J Surg Res. 2017;219:360-365. doi:10.1016/j.jss.2017.06.049
12. 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
13. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332(20):1330-1335. doi:10.1056/NEJM199505183322003
14. Byrne JP, Geerts W, Mason SA, et al. Effectiveness of low-molecular-weight heparin versus unfractionated heparin to prevent pulmonary embolism following major trauma: A propensity-matched analysis. J Trauma Acute Care Surg. 2017;82(2):252-262. doi:10.1097/TA.0000000000001321
15. Knudson MM, Morabito D, Paiement GD, Shackleford S. Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma. 1996;41(3):446-459. doi:10.1097/00005373-199609000-00010
16. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 1996;335(10):701-707. doi:10.1056/NEJM199609053351003
17. Schellenberg M, Benjamin E, Inaba K, et al. When Is It Safe to Start Pharmacologic Venous Thromboembolism Prophylaxis After Pelvic Fractures? A Prospective Study From a Level I Trauma Center. J Surg Res. 2021;258:272-277. doi:10.1016/j.jss.2020.08.077
18. Tsiridis E, Gamie Z, George MJ, Hamilton-Baille D, West RM, Giannoudis PV. Early postoperative bleeding in polytrauma patients treated with fondaparinux: literature review and institutional experience. Curr Vasc Pharmacol. 2011;9(1):42-47. doi:10.2174/157016111793744670
19. Lu J-P, Knudson MM, Bir N, Kallet R, Atkinson K. Fondaparinux for prevention of venous thromboembolism in high-risk trauma patients: a pilot study. J Am Coll Surg. 2009;209(5):589-594. doi:10.1016/j.jamcollsurg.2009.08.001
20. Kanakaris NK, Nikolaou VS, Tosounidis T, Giannoudis PV. Fondaparinux for the prevention or treatment of venous thromboembolism related to lower limb trauma: evidence today. Curr Vasc Pharmacol. 2008;6(2):134-142. doi:10.2174/157016108783955293
21. Sekharan J, Dennis JW, Miranda FE, et al. Long-term follow-up of prophylactic greenfield filters in multisystem trauma patients. J Trauma. 2001;51(6):1087-1090; discussion 1090-1091. doi:10.1097/00005373-200112000-00012
22. Kakkos SK, Caprini JA, Geroulakos G, et al. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. Cochrane Database Syst Rev. 2016;9:CD005258. doi:10.1002/14651858.CD005258.pub3
23. Fisher CG, Blachut PA, Salvian AJ, Meek RN, O’Brien PJ. Effectiveness of pneumatic leg compression devices for the prevention of thromboembolic disease in orthopaedic trauma patients: a prospective, randomized study of compression alone versus no prophylaxis. J Orthop Trauma. 1995;9(1):1-7. doi:10.1097/00005131-199502000-00001
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