 EDITORIAL

Thromboprophylaxis for patients undergoing joint replacement

R. L. Barrack From Washington University School of Medicine, St Louis, United States

 R. L. Barrack, MD, Charles and Joanne Knight Distinguished Professor, Chief of Service Washington University School of Medicine, Department of Orthopaedic Surgery, Washington University School of Medicine, One Barnes Jewish Hospital Plaza, 11300 West Pavilion, Campus Box 8233, St. Louis, MO 63110, USA. Correspondence should be sent to Mr R. L. Barrack; e-mail: [email protected] ©2014 The British Editorial Society of Bone & Joint Surgery doi:10.1302/0301-620X.96B1. 33459 $2.00 Bone Joint J 2014;96-B:3–4.

In his classic monograph entitled Low Friction Arthroplasty of the Hip, which was published in 1979, John Charnley dedicated a chapter to thromboembolic complications.1 He tried a number of drug regimens with varying degrees of success. Among the drugs he tried was Plaquenil (Sanofi-Aventis, Bridgewater, New Jersey), which was later recognised to be suboptimal for preventing venous thromboembolism (VTE) however, it was noted that the incidence of malaria in Wrightington during that time period was extremely low. The overall incidence of pulmonary embolism (PE) was approximately 8% and the incidence of death from PE approximately 1%. Among the patients who received no prophylaxis, however, the complication rate was twice as high, leading Charnley to state, “the use of an untreated control group is no longer acceptable.” So while it was recognised that some method of prophylaxis should be employed in all patients, there was no resolution as to what form it should take. Surveys of orthopaedic surgeons who undertake total joint replacement conducted by The American Association of Hip and Knee Surgeons (AAHKS), 30 years later, showed that there was still no consensus as to the best form of prophylaxis with a wide variation of methods being used. The conclusion was that “there is no one best method of prophylaxis.”2 There was a similar lack of uniformity in the approach to thromboprophylaxis in other medical and surgical specialities. This led to a concern that VTE was a significant threat to hospitalised patients, and some uniformity of approach was needed to minimise the risk to both medical and surgical patients. This relative vacuum was filled by the American College of Chest Physicians (ACCP) who held their first conference in 1985. This group is predominantly one of internal medicine specialists, although it includes a few surgeons. In spite of the relative lack of experience in treating peri-operative patients, particularly those in orthopaedic surgery, the ACCP eventually released guidelines for a number of medical and surgical specialties, including orthopaedic surgery. There was, however, not an orthopaedic

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surgeon among the authors of the guidelines until the sixth conference, in which all patients undergoing hip and knee replacement were placed in the highest risk category.3 In the seventh conference, in 2004, many recommendations were made based on the criteria that were established for the studies that were analysed. The highest level of recommendation was that of a 1A, which required prospective, multi-centred, randomised, clinical trials with venography to establish an incidence of deep vein thrombosis (DVT) as an endpoint, whether or not a symptomatic event had occurred. The agents that were recommended in this category for hip and knee replacement were warfarin, with a target INR of 2 to 3, low-molecular-weight heparin, or Fondaparinux.4 In the year following the release of the ACCP guidelines, an editorial written by several prominent American orthopaedic surgeons who specialised in joint replacement appeared in the Journal of Arthroplasty.5 They expressed several concerns with the ACCP guidelines, including caution when specialists from one subspeciality recommend forms of treatment for another, caution when considering guidelines based entirely on the reduction of the rate of DVT, which may not correlate with symptomatic events, including PE and death, and concern that a focus on reduction of DVT with aggressive chemoprophylaxis would lead to much higher risk of bleeding and associated morbidity.5 Soon after the publication of the seventh ACCP conference, a study was undertaken at The Barnes-Jewish Hospital to assess a 1A protocol. Lovenox (enoxaparin) was administered to all patients undergoing joint replacement after consent to participate in an ethically approved study that assessed wound drainage, symptomatic events, hospital re-admission, injection site problems, and wound-related problems. Data were collected on < 300 patients, although, the original study anticipated evaluating > 2000 patients. The study was terminated owing to concerns for patient safety, and the results were compared with a previous study from the same institution.6 The incidence 3

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of major and minor complications was much higher in the Lovenox group compared with the prior cohort using lowdose Coumadin (warfarin) for one week followed by ultrasound screening. The results of the prior prophylaxis protocol had been published.7 Excellent results were obtained with a non-approved protocol, and inferior results were observed shortly thereafter with an ethically approved study using an ACCP 1A protocol. The following year, virtually identical results were reported from the University of Virginia.8 In response to the concerns with the ACCP guidelines, the American Academy of Orthopaedic Surgeons (AAOS) established a working group on VTE, which evaluated available data with the endpoints of symptomatic events rather than DVT. The original working group considered PE and death, with a second working group, in 2011, considering symptomatic DVT, as well. When only symptomatic events were considered, the resulting conclusion was that the data available were not adequate to support any of the commonly used prophylactic measures over another, including low-molecularweight heparin, Xa inhibitors, direct-thrombin inhibitors, aspirin and pneumatic compression devices among others. A risk stratification approach was recommended with more aggressive prophylaxis to be used in patients at risk (with the major risk factor being that of prior VTE) and less aggressive prophylaxis in patients with a known bleeding disorder.9 This placed the AAOS in direct conflict with the ACCP and all of their major recommendations. In 2012, the ACCP re-evaluated their methodology, and in accordance with the AAOS, agreed to focus on symptomatic VTE and minimising bleeding complications. The resulting recommendations no longer contained any recommendations at the 1A levels, since there were inadequate data from multi-centred, randomised trials with symptomatic events as an endpoint to justify a 1A recommendation. 1B recommendations included all commonly used anticoagulants, including aspirin. Pneumatic compression devices were included at the 1C level. When a pneumatic compression device is used, a mobile device that allows at least ten days of continuous use with a monitoring chip was recommended. Since the AAOS guidelines were released, excellent results have been reported with the use of aspirin in patients without major risk factors at one major orthopaedic centre in the U.S.10 Also, a multi-centre study using the mobile compression device demonstrated excellent efficacy and safety with an incidence of symptomatic events as low as any reported with the use of aggressive pharmacoprophylaxis.11 In the past year, for the first time there is uniformity in the recommendations of the AAOS and the ACCP. Both groups have reached an agreement that the rate of DVT formation is not the ideal endpoint to use when assessing the efficacy of thromboprophylaxis after joint replacement, as had been done in previous drug trials.12 Most of these DVTs are asymptomatic and of questionable clinical significance. At least one recent study brings into question the association between the rate of DVT formation and that of subsequent symptomatic events.10 Both groups

also focus on minimising iatrogenic bleeding complications, which can lead to compromised clinical results, including limited movement and pain in the case of knee replacement and increased risk of infection in both knee and hip replacement.13-15 To further complete the uniformity of approach in the United States, the Center for Medicare and Medicaid Services (CMS), which administers the Surgical Care Improvement Program (SCIP) that monitors hospital compliance with VTE prophylaxis of hospitalised patients, has also changed their policy. It was recently announced that beginning January, 2014, either aspirin or a compression device will be considered as acceptable measures for THR, TKR and hip fracture.16 The remarkable success reported from many centres17-19 with the use of aspirin and/or the use of a mobile compression device in patients without major risk factors, such as a prior history of symptomatic VTE, clearly indicate that aggressive pharmacoprophylaxis is not necessary for the vast majority of patients who undergo joint replacement.

References 1. Charnley J. Low friction arthroplasty of the hip: theory and practice. Berlin:Springer-Verlag, 1979:308–313. 2. Mesko JW, Brand RA, Iorio R, et al. Venous thromboembolic disease management patterns in total hip arthroplasty and total knee arthroplasty patients: a survey of the AAHKS membership. J Arthroplasty 2001;16:679–688. 3. Haas S. Prevention of venous thromboembolism: recommendations based on the international consensus and the American College of Chest Physicians sixth consensus conference on antithrombotic therapy. Clin Appl Thromb Hemost 2001;7:171–177. 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(Suppl):338–400. 5. Callaghan JJ, Dorr LD, Engh GA, et al. Prophylaxis for thromboembolic disease: recommendations from the American College of Chest Physicians—are they appropriate for orthopaedic surgery? J Arthoplasty 2005;20(3):273–274. 6. Burnett RS, Clohisy JC, Wright RW, et al. Failure of the American College of Chest Physicians-1A protocol for lovenox in clinical outcomes for thromboembolic prophylaxis. J Arthroplasty 2007;22:317–324. 7. Keeney JA, Clohisy JC, Curry MC, Maloney WJ. Efficacy of combined modality prophylaxis including short-duration warfarin to prevent venous thromboembolism after total hip arthroplasty. J Arthroplasty 2006;21:469–475. 8. Novicoff WM, Brown TE, Cui Q, et al. Mandated venous thromboembolism prophylaxis: possible adverse outcomes. J Arthroplasty 2008;23(Suppl):15–19. 9. 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-A:746–747. 10. Parvizi J, Jacovides CL, Bican O, et al. Is deep vein thrombosis a good proxy for pulmonary embolus? J Arthroplasty 2010;25(Suppl):138–144. 11. Colwell CW, Froimson MI, Anseth SD, et al. A mobile compression device for thrombosis prevention in hip and knee arthroplasty. J Bone Joint Surg [Am];in press. 12. Falck-Yher Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopaedic surgery patients: Antithrombolic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. Chest 2013;14(2 Suppl):e2785–3255. 13. Wang Z, Anderson, FA, Ward MM, Bhattacharyya T. Association between surgical site infections and anticoagulant thromboprophylaxis following elective THA or TKA [abstract]. Posters and Scientific Exhibits AR HIP, 2013. 14. Saleh K, Olson M, Resig S, et al. Predictors of wound infection in hip and knee joint replacement: results from a 20 year surveillance program. J Orthop Res 2002;20:506–515. 15. Patel VP, Walsh M, Sehgal B, et al. Factors associated with prolonged wound drainage after primary total hip and knee arthroplasty. J Bone Joint Surg [Am] 2007;89-A:33–38. 16. McKee J. SCIP VTE Measures Changing in 2014: New measures go into effect on Jan. 1, 2014. AAOS Now (online)2013;7: http://www.aaos.org/news/aaosnow/nov13/ cover2.asp (date last accessed 28 November 2013). 17. Bozic KJ, Vail TP, Pekow, et al. Does aspirin have a role in venous thromboembolism, prophylaxis in total knee arthroplasty patients? J Arthroplasty 2010;25:1053–1060. 18. Callaghan JJ, Warth LC, Hoballah JJ, Liu SS, Wells CW. Evaluation of deep venous thrombosis proplylaxis in low-risk patients undergoing total knee arthroplasty. J Arthroplasty 2008;23:20–24. 19. Lotke PA, Lonner JH. The benefit of aspirin chemoprophylaxis for thromboembolism after total knee arthroplasty. Clin Orthop Relat Res 2006;452:175–180. THE BONE & JOINT JOURNAL