11 – Does the administration of VTE prophylaxis to patients undergoing orthopedic procedures increase the rate of post-operative non-VTE complications?

Jean-Yves Jenny.

Response/Recommendation: Administration of pharmacological venous thromboembolism (VTE) prophylaxis to patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) increases the rate of post-operative bleeding complications. Potent anticoagulants may be more at risk than aspirin (ASA). The literature is inconclusive for other orthopaedic procedures.

Strength of Recommendation: Strong.

Rationale: Although compressive stockings and fast-track rehabilitation are effective in reducing the incidence of VTE1, routine pharmacological VTE prophylaxis is generally recommended2. Current recommendations provide a list of procedures requiring VTE prophylaxis, focusing on THA or TKA and proximal hip fracture2,3. However, there is a general trend to extend the pharmacological VTE prophylaxis to other procedures based on perceived level of risk4. Commonly used agents include: Low-molecular-weight heparin (LMWH), fondaparinux, direct oral anticoagulant (DOAC), low-dose unfractionated heparin, adjusted-dose or low-dose vitamin K antagonist, or ASA2,3.

There is no evidence in the literature that nonpharmacological VTE prophylaxis (mechanical compression, early ambulation, fast-track procedures) increases the risk of post-operative complications5–8.

In contrast, the use of any pharmacological agent involves risk. Some complications such as heparin-induced thrombocytopenia are rare. Excess bleeding is the major risk which can manifest as an increase in wound discharge9. Haematoma formation may require further surgery or allogeneic transfusion10 both of which can increase the rate of surgical site infection11–14.

There is extensive literature for THA and TKA. While the risk of VTE events is currently decreasing, probably because of the more frequent use of fast-track procedures, the risk of bleeding remains unchanged7. The risk for bleeding without VTE prophylaxis remains difficult to estimate because modified operative and recovery techniques may make the untreated bleeding event rate deriving from the placebo group of past studies2. There are only few recent studies including a control group without pharmacological VTE prophylaxis15–17. The increased bleeding risk18,19 may not be compensated for by the administration of tranexamic acid18. However, the routine use of tranexamic acid and more restrictive transfusion policy has dramatically decreased the need for transfusion after primary THA and TKA20, and the impact of VTE prophylaxis may be difficult to assess.

The risk may be further increased when potent anticoagulants drugs are administered in comparison to ASA21–23, but some authors report conflicting results24, and the rates may be different for THA and TKA6. There is little evidence that different potent anticoagulants agents other than ASA are associated with different risks of bleeding25,26.

Early readmission and repeat surgery rates after primary THA or TKA are affected by the occurrence of bleeding and wound discharge27. As bleeding and wound discharge are more frequent with pharmacological VTE prophylaxis, readmission and further surgery rates may be higher as well.

There is a paucity of recent literature for other orthopaedic procedures than THA and TKA, and no scientifically supported conclusion can be suggested.

References:

1.         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. Surgeon. 2020;18(4):219-225. doi:10.1016/j.surge.2019.11.002

2.         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

3.         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

4.         Kim S, Ahn H, Shin S-A, Park J-H, Won CW. Trends of thromboprophylaxis and complications after major lower limb orthopaedic surgeries in Korea: National Health Insurance Claim Data. Thromb Res. 2017;155:48-52. doi:10.1016/j.thromres.2017.04.023

5.         Arsoy D, Giori NJ, Woolson ST. Mobile Compression Reduces Bleeding-related Readmissions and Wound Complications After THA and TKA. Clin Orthop Relat Res. 2018;476(2):381-387. doi:10.1007/s11999.0000000000000041

6.         Colwell CW, Froimson MI, Mont MA, et al. Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin. J Bone Joint Surg Am. 2010;92(3):527-535. doi:10.2106/JBJS.I.00047

7.         Jenny J-Y, Bulaid Y, Boisrenoult P, et al. Bleeding and thromboembolism risk of standard antithrombotic prophylaxis after hip or knee replacement within an enhanced recovery program. Orthop Traumatol Surg Res. 2020;106(8):1533-1538. doi:10.1016/j.otsr.2020.02.026

8.         Jørgensen CC, Jacobsen MK, Soeballe K, et al. Thromboprophylaxis only during hospitalisation in fast-track hip and knee arthroplasty, a prospective cohort study. BMJ Open. 2013;3(12):e003965. doi:10.1136/bmjopen-2013-003965

9.         Bloomfield MR, Patterson RW, Froimson MI. Complications of anticoagulation for thromboembolism in early postoperative total joint arthroplasty. Am J Orthop (Belle Mead NJ). 2011;40(8):E148-151.

10.       Holt JB, Miller BJ, Callaghan JJ, Clark CR, Willenborg MD, Noiseux NO. Minimizing Blood Transfusion in Total Hip and Knee Arthroplasty Through a Multimodal Approach. J Arthroplasty. 2016;31(2):378-382. doi:10.1016/j.arth.2015.08.025

11.       Kim JL, Park J-H, Han S-B, Cho IY, Jang K-M. Allogeneic Blood Transfusion Is a Significant Risk Factor for Surgical-Site Infection Following Total Hip and Knee Arthroplasty: A Meta-Analysis. J Arthroplasty. 2017;32(1):320-325. doi:10.1016/j.arth.2016.08.026

12.       Everhart JS, Sojka JH, Mayerson JL, Glassman AH, Scharschmidt TJ. Perioperative Allogeneic Red Blood-Cell Transfusion Associated with Surgical Site Infection After Total Hip and Knee Arthroplasty. J Bone Joint Surg Am. 2018;100(4):288-294. doi:10.2106/JBJS.17.00237

13.       Cimminiello C, Prandoni P, Agnelli G, et al. Thromboprophylaxis with enoxaparin and direct oral anticoagulants in major orthopedic surgery and acutely ill medical patients: a meta-analysis. Intern Emerg Med. 2017;12(8):1291-1305. doi:10.1007/s11739-017-1714-9

14.       Brimmo O, Glenn M, Klika AK, Murray TG, Molloy RM, Higuera CA. Rivaroxaban Use for Thrombosis Prophylaxis Is Associated With Early Periprosthetic Joint Infection. J Arthroplasty. 2016;31(6):1295-1298. doi:10.1016/j.arth.2015.12.027

15.       Malhotra K, Marciniak JL, Bonczek SJ, Hunt N. Venous thromboembolism after lower limb arthroplasty: is chemical prophylaxis still needed? Eur J Orthop Surg Traumatol. 2016;26(8):895-899. doi:10.1007/s00590-016-1820-9

16.       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

17.       Yassin M, Mitchell C, Diab M, Senior C. The necessity of pharmacological prophylaxis against venous thromboembolism in major joint arthroplasty. Int Orthop. 2014;38(5):1073-1075. doi:10.1007/s00264-013-2233-6

18.       Sharfman ZT, Campbell JC, Mirocha JM, Spitzer AI. Balancing Thromboprophylaxis and Bleeding in Total Joint Arthroplasty: Impact of Eliminating Enoxaparin and Predonation and Implementing Pneumatic Compression and Tranexamic Acid. J Arthroplasty. 2016;31(6):1307-1312. doi:10.1016/j.arth.2015.11.046

19.       Suen K, Westh RN, Churilov L, Hardidge AJ. Low-Molecular-Weight Heparin and the Relative Risk of Surgical Site Bleeding Complications: Results of a Systematic Review and Meta-Analysis of Randomized Controlled Trials of Venous Thromboprophylaxis in Patients After Total Joint Arthroplasty. J Arthroplasty. 2017;32(9):2911-2919.e6. doi:10.1016/j.arth.2017.04.010

20.       Jeschke E, Citak M, Halder AM, et al. Blood transfusion and venous thromboembolism trends and risk factors in primary and aseptic revision total hip and knee arthroplasties: A nationwide investigation of 736,061 cases. Orthop Traumatol Surg Res. Published online June 16, 2021:102987. doi:10.1016/j.otsr.2021.102987

21.       Garfinkel JH, Gladnick BP, Roland N, Romness DW. Increased Incidence of Bleeding and Wound Complications With Factor-Xa Inhibitors After Total Joint Arthroplasty. J Arthroplasty. 2018;33(2):533-536. doi:10.1016/j.arth.2017.08.039

22.       Jones CW, Spasojevic S, Goh G, Joseph Z, Wood DJ, Yates PJ. Wound Discharge After Pharmacological Thromboprophylaxis in Lower Limb Arthroplasty. J Arthroplasty. 2018;33(1):224-229. doi:10.1016/j.arth.2017.07.046

23.       He T, Han F, Wang J, Hu Y, Zhu J. Efficacy and safety of anticoagulants for postoperative thrombophylaxis in total hip and knee arthroplasty: A PRISMA-compliant Bayesian network meta-analysis. PLoS One. 2021;16(6):e0250096. doi:10.1371/journal.pone.0250096

24.       Matharu GS, Garriga C, Whitehouse MR, Rangan A, Judge A. Is Aspirin as Effective as the Newer Direct Oral Anticoagulants for Venous Thromboembolism Prophylaxis After Total Hip and Knee Arthroplasty? An Analysis From the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man. J Arthroplasty. 2020;35(9):2631-2639.e6. doi:10.1016/j.arth.2020.04.088

25.       Watts PJ, Kopstein M, Harkness W, et al. A retrospective analysis of bleeding risk with rivaroxaban, enoxaparin, and aspirin following total joint arthroplasty or revision. Pharmacotherapy. 2021;41(7):608-615. doi:10.1002/phar.2599

26.       Liu J, Zhao J, Yan Y, Su J. Effectiveness and safety of rivaroxaban for the prevention of thrombosis following total hip or knee replacement: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(9):e14539. doi:10.1097/MD.0000000000014539

27.       Phruetthiphat O-A, Otero JE, Zampogna B, Vasta S, Gao Y, Callaghan JJ. Predictors for readmission following primary total hip and total knee arthroplasty. J Orthop Surg (Hong Kong). 2020;28(3):2309499020959160. doi:10.1177/2309499020959160