The prevention of venous thromboembolism and the risk of postoperative complications in patients with rheumatoid arthritis and osteoarthritis after total hip arthroplasty

Patients who have undergone large (hip, knee) joint replacement constitute a group at high risk for developing venous thromboembolic events (VTEs). According to different authors, the risk of nonpreventable VTEs in these patients varies from 40 to 80%.
Objective: to analyze the incidence of VTE and the risk of postoperative wound-related bleeding and complications in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) after total hip arthroplasty.
Subjects and methods. The investigation enrolled 486 patients with RA (n=212) and OA (n=274) who underwent primary hip arthroplasty. Each patient group was divided into three subgroups according to prevention with the following drugs: 1) nadroparin calcium; 2) dabigatran etexilate; 3) nadroparin calcium switched to dabigatran etexilate. According to the International Society on Thrombosis and Haemostasis criteria, intra- and postoperative blood loss was assessed during the first 7 days after surgery; the wound healing process was also evaluated.
Results and discussion. VTE was prevented with the drugs in 239 (49.2%) patients, 130 (26.8%) of them received nadroparin calcium, the remaining 117 (24.0%) patients had dabigatran etexilate or both drugs. Postoperative VTEs were recorded in 36 (7.4%) out of the 486 patients. VTEs were detected significantly less frequently In RA than in OA (1.2 and 6.1%, respectively; p=0.0013). VTEs were more commonly asymptomatic in both groups. No fatal bleeding was seen in any patient, which confirms the safety of anticoagulant therapy. Blood transfusions were more frequently given to bleeding patients with RA than to those with OA (14.4 and 5.7% of cases, respectively; p<0.001). The number of patients with RA who required discontinuation of anticoagulant therapy was more than those with OA (6.6% and 1.4%, respectively). Delayed wound healing was also much more common in patients with RA (n=56; 26.4%) than in those with OA (n=14; 5.1%). VTE occurred much more often in patients receiving monotherapy with nadroparin calcium than in those having combined therapy (p<0.0001), and somewhat more frequently than in those taking dabigatran etexilate (p=0.054), however, the difference for the latter did not reach statistical significance.
Conclusion. During elective hip replacement, VTEs occurred less frequently in patients with RA than in those with OA (1.23 and 6.17%, respectively, p=0.0013). After hip arthroplasty, VTEs were detected significantly more often in nadroparin calcium-treated patients with RA and OA than in patients receiving combined therapy. Postoperative wound-related bleedings were significantly more frequently observed in RA than in OA (14.4 and 5.7% of cases, respectively). The risk of postoperative wound-related complications in RA is much higher than in OA (relative risk, 4.33; 95% confidence interval, 2.67–7.03; p<0.001), which increases the length of hospital stay and the cost of the treatment performed.

1. Lee JJ, Pope JE. A meta-analysis of the risk of venous thromboembolism in inflammatory rheumatic diseases. Arthritis Res Ther. 2014;16(5):435 doi: 10.1186/s13075-014-0435-y

2. Matta F, Singala R, Yaekoub AY, et al. Risk of venous thromboembolism with rheumatoid arthritis. Thromb Haemost. 2009;101(1):134-8. doi: 10.1160/TH08-08-0551

3. Kim SC, Schneeweiss S, Liu J, Solomon DH. Risk of venous thromboembolism in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65(10):1600-7. doi: 10.1002/acr.22039

4. Bacani AK, Gabriel SE, Crowson CS, et al. Noncardiac vascular disease in rheumatoid arthritis: increase in venous thromboembolic events? Arthritis Rheum. 2012;64(1):53-61. doi: 10.1002/art.33322

5. Pederson AB, Sorensen HT, Mehnart F, et al. Risk factors for venous thromboembolism inpatients undergoing total hip replacement and receiving routine thromboprophilaxis. J Bone Joint Surg Am. 2010;92:2156-64. doi: 10.2106/JBJS.I.00882

6. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений. Флебология. 2015;2(4):37 [Russian clinical guidelines for the diagnosis, treatment and prevention of venous thromboembolic complications. Flebologiya = Phlebology. 2015;2(4):37 (In Russ.)].

7. Рыбников АВ, Бялик ЕИ, Решетняк ТМ и др. Эффективность профилактики венозных тромбоэмболических осложнений при эндопротезировании крупных суставов у больных ревматоидным артритом и остеоартрозом. Политравма. 2016;(2):48-54 [Rybnikov AV, Byalik EI, Reshetnyak TM, et al. The effectiveness of the prevention of venous thromboembolic complications in endoprosthetics of large joints in patients with rheumatoid arthritis and osteoarthrosis. Politravma. 2016;(2):48-54 (In Russ.)].

8. 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 Suppl. 6:382-453. doi: 10.1378/chest.08-0656

9. 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 Feb;141(2 Suppl):e278S-e325S. doi: 10.1378/chest.11-2404

10. Prevoo ML, van't Hof MA, Kuper HH, et al. Modified disease activity scores that include twenty-eigth-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44-8. doi: 10.1002/art.1780380107

11. Schulman S, Angeras U, Bergqvist D, et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010;8:202-4. doi: 10.1111/j.1538-7836.2009.03678.x

12. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in nonsurgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015;13:2119-26. doi: 10.1111/jth.13140

13. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in in patients with atrial fibrillation: the Euro Heart Survey on atrial fibrillation. Chest. 2010;138:1093-100. doi: 10.1378/chest.10-0134

14. Johanson N, Lachiewicz PF, Licbcrman JR, et al. Prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroscopy. J Am Acad Orthop Surg. 2009;17(17):183-96. doi: 10.2106/JBJS.I.00511

15. Mochizuki T, Ikari K, Yano K, et al. Outcome of Direct Oral Anticoagulant Treatment for Acute Lower Limb Deep Venous Thrombosis After Total Knee Arthroplasty Or Total Hip Arthroplasty. Mod Rheumatol. 2018;1:1-5. doi: 10.1080/14397595.2018.1504396

16. Januel JM, Romano PS, Couris CM, et al. Clinical and Health System Determinants of Venous Thromboembolism Event Rates After Hip Arthroplasty: An International Comparison. International Methodology Consortium for Coded Health Information (IMECCHI). Med Care. 2018;56(10):862-9. doi: 10.1097/MLR.000000000000095

17. D'Angelo A, Kluft C, Verheijen J, et al. Fibrinolytic shut down after surgery: impairment of the balance between tissue-type plasminogen activator and its specific inhibitor. Eur J Clin Invest. 1985;15:308-12 doi: 10.1111/j.1365-2362.1985.tb00277

18. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336(14):973-9. doi: 10.1056/NEJM199704033361401

19. Folsom AR, Lutsey PL, Astor BC, Cushman M. C-reactive protein and venous thromboembolism. A prospective investigation in the ARIC cohort. Thromb Haemost. 2009;102(4):615-9. doi: 10.1160/TH09-04-0274

20. Kamphuisen PW, Eikenboom JC, Vos HL, et al. Increased levels of factor VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions. Thromb Haemost. 1999;81(5):680-3. doi: 10.1055/s-0037-1614553

21. Zacho J, Tybjaerg-Hansen A, Nordestgaard BG. C-reactive protein and risk of venous thromboembolism in the general population. Arterioscler Thromb Vasc Biol. 2010;30(8):1672-8. doi: 10.1161/ATVBAHA.109.198473

22. Vormittag R, Vukovich T, Schonauer V, et al. Basal high-sensitivity-C-reactive protein levels in patients with spontaneous venous thromboembolism. Thromb Haemost. 2005;93(3):488-9. doi: 10.1160/TH04-11-0745

23. Kaplan MJ, Salmon JE. How does interferon-alpha insult the vasculature? Let me count the ways. Arthritis Rheum. 2011;63(2):334-6. doi: 10.1002/art.30161

24. Dessein PH, Solomon A, Woodiwiss AJ, et al. Marked independent relationship between circulating interleukin-6 concentrations and endothelial activation in rheumatoid arthritis. Mediat Inflamm. 2013;2013:Article ID 510243. doi: 10.1155/2013/510243

25. Wakefield TW, Myers DD, Henke PK. Mechanisms of venous thrombosis and resolution. Arterioscler Thromb Vasc Biol. 2008;28(3):387-91. doi: 10.1161/ATVBAHA.108.162289

26. Zoller B, Li X, Sundquist J, Sundquist K. Autoimmune diseases and venous thromboembolism: a review of the literature. Am J Cardiovasc Dis. 2012;2(3):171-83.

27. Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010;375:657-63. doi: 10.1016/S0140-6736(09)61963-2

28. Niki Y, Matsumoto H, Hakozaki A, et al. Rheumatoid arthritis: a risk factor for deep venous thrombosis after total knee arthroplasty? Comparative study with osteoarthritis. J Orthop Sci. 2010;15(1):57-63. doi: 10.1007/s00776-009-1410-3

29. Ravi B, Croxford R, Hollands S, et al. Increased risk of complications following total joint arthroplasty in patients with rheumatoid arthritis. Arthritis Rheum. 2014;66(2):254-63. doi: 10.1002/art.38231

30. White RH, Gettner S, Newman JM, et al. Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med. 2000;343(24):1758-64. doi: 10.1056/NEJM200012143432403

31. Lee JK, Choi CH. Total knee arthplasty in Rheumatoid arthritis. Knee Surg Relat Res. 2012;24:1-6. doi: 10.5792/ksrr.2012.24.1.1

32. Schü ttler KF, Schramm R, El-Zayat BF, et al. The effect of surgeon's learning curve: complications and outcome after hip arthroscopy. Arch Orthop Trauma Surg. 2018;138(10):1415-21. doi: 10.1007/s00402-018-2960-7

33. Lindquist DE, Stewart DW, Brewster A, et al. Comparison of Postoperative Bleeding in Total Hip and Knee Arthroplasty Patients Receiving Rivaroxaban, Enoxaparin, or Aspirin for Thromboprophylaxis. Clin Appl Thromb Hemost. 2018;24(8):1315-21. doi: 10.1177/1076029618772337

34. Grennan DM, Gray J, Loudon J, Fear S. Metotrexat and early postoperative complications in patients with Rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheumatic Dis. 2001;60:214-7 doi: 10.1136/ard.60.3.214

35. Danoff JR, Moss C, Liabaud B, Geller JA. Total knee arthroplasty considerations in Rheumatoid Arthritis. Autoimmun Dis. 2013;2013:Article ID 185340, 6 p. doi: 10.1155/2013/185340

36. Храмов АЭ, Макаров МА, Бялик ЕИ и др. Проблемы диагностики, профилактики и лечения перипротезной инфекции у больных ревматическими заболеваниями. Научно-практическая ревматология. 2015;53(5):558-63 [Khramov AE, Makarov MA, Byalik EI, et al. Periprosthetic joint infection in patients with rheumatic diseases: The problems of diagnosis, prevention, and treatment. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(5):558-63 (In Russ.)]. doi: 10.14412/1995-4484-2015-558-563

37. LoVerde ZJ, Mandl LA, Johnson BK, et al. Rheumatoid arthritis does not increase risk of short-term adverse events after total knee arthroplasty: a retrospective case-control study. J Rheumatol. 2015;42(7):1123-30. doi: 10.3899/jrheum.141251

38. Храмов АЭ, Макаров МА, Макаров СА и др. Местные осложнения эндопротезирования тазобедренного и коленного суставов у пациентов с ревматоидным артритом и остеоартритом. Научно-практическая ревматология. 2017;55(5):549-54 [Khramov AE, Makarov MA, Makarov SA, et al. Local complications of hip and knee joint replacement in patients with rheumatoid arthritis and osteoarthritis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(5):549-54 (In Russ.)]. doi: 10.14412/1995-4484-2017-549-554

39. Izumi M, Migita K, Nakamura M, et al. Risk of venous thromboembolism after total knee arthroplasty in patients with rheumatoid arthritis. J Rheumatol. 2015;42(6):928-34. doi: 10.3899/jrheum.140768