Crispiana Cozowicz, Jashvant Poeran, Stavros Memtsoudis.
Response/Recommendation: Following major orthopaedic surgery venous thromboembolism (VTE) prophylaxis -initiated in-hospital- should be continued for 14 to 35 days after patient discharge.
Strength of Recommendation: Strong.
Rationale: The occurrence of VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE) is a relatively major source of perioperative morbidity, mortality and healthcare cost in lower joint arthroplasty surgery.1-3 Hence, numerous organizations, including the American Academy of Orthopaedic Surgeons (AAOS), have provided guidelines for prevention of VTE following total joint arthroplasty4. However, a general consensus on the type and the duration of VTE prophylaxis following orthopaedic procedures remains disputed.2,5,6.
Guidelines by the American College of Chest Physicians (ACCP) recommend the use of chemo-thromboprophylaxis for a minimum of ten days after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in addition to early mobilization7. In previous trials, VTE prophylaxis was mostly given until hospital discharge, ranging from 7 to 14 days. Meanwhile, however, the length of hospitalization for most major orthopaedic surgeries has significantly decreased, rendering VTE prophylaxis limited to the hospitalization period insufficient8.
Moreover, several studies have shown a second peak in the rate of postoperative DVT incidence in the late postoperative period, after termination of chemothromboprophylaxis3.
This delayed thromboembolism suggests that VTE risk extends beyond the hospitalization period8-11. The underlying mechanism may be based on the assumption that surgery-induced activation of the coagulation and fibrinolysis cascade at a local and systemic level persists for an extended period10. While the optimal duration for VTE prophylaxis remains uncertain, it has been suggested that this second risk period may occur between the second and the fifth postoperative week9,10. Moreover, coagulation indicators in the plasma have shown that a substantial hypercoagulability is sustained until day 35 after THA, despite the verified lack of thrombosis at hospital discharge12,13. Continuation of thromboprophylaxis after discharge, however, appears to significantly reduce the incidence of DVT and PE in major orthopaedic surgery11,14.
Given the growing body of evidence in support of persisting thromboembolic risk after hospital discharge in major orthopaedic surgery, we conducted a systematic review and meta-analysis on the direct comparative effectiveness of extended (versus short-term or in-hospital) VTE prophylaxis.
The current body of evidence consists of 19 randomized controlled trials (RCT) of high to moderate quality and one non-randomized study. Summaries and meta-analyses can be found in the Appendix. Pooled meta-analysis of RCT only, demonstrated that VTE prophylaxis, when extended for up to 6 weeks beyond hospital discharge, significantly reduced the risk for the occurrence of symptomatic and asymptomatic DVT compared to short-term regimens. The odds of a postoperative DVT were reduced by 64% in THA and by 28% in TKA recipients with VTE prophylaxis extended for several weeks beyond hospital discharge. Statistical heterogeneity within the study sample was low, despite individual trial differences with regards to duration of prophylaxis (2 – 6 weeks) and variations of utilized anticoagulant drugs (unfractionated heparin, low-molecular-weight heparin, and oral anticoagulants). The benefit of extended VTE prophylaxis was observed without an increased risk for major bleeding. More research is needed to establish the comparative effectiveness between individual anticoagulant medications15.
Notably, cohort studies arguing against the need for out of hospital prophylaxis are of low-quality evidence16,17.
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3. Haentjens P. Venous thromboembolism after total hip arthroplasty. A review of incidence and prevention during hospitalization and after hospital discharge. Acta Orthop Belg 2000;66:1-8.
4. Mont MA, Jacobs JJ. Aaos clinical practice guideline: Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg 2011;19:777-8.
5. Mont M, Jacobs J, Lieberman J et al. Preventing venous thromboembolic disease in patients undergoing elective total hip and knee arthroplasty. The Journal of Bone and Joint Surgery American volume 2012;94:673.
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14. Dahl OE, Aspelin T, Arnesen H et al. Increased activation of coagulation and formation of late deep venous thrombosis following discontinuation of thromboprophylaxis after hip replacement surgery. Thromb Res 1995;80:299-306.
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16. Hull RD, Pineo GF, Francis C et al. Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: A double-blind, randomized comparison. North american fragmin trial investigators. Arch Intern Med 2000;160:2208-15.
17. Pedersen AB, Andersen IT, Overgaard S et al. Optimal duration of anticoagulant thromboprophylaxis in total hip arthroplasty: New evidence in 55,540 patients with osteoarthritis from the nordic arthroplasty register association (nara) group. Acta Orthop 2019;90:298-305.
18. Eriksson BI, Lassen MR. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: A multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med 2003;163:1337-42.
19. Kawaji H, Ishii M, Tamaki Y et al. Postoperative prophylactic effect of fondaparinux for prevention of deep venous thrombosis after cemented total hip replacement: A comparative study. Modern rheumatology 2012;22:216-22.
20. Comp PC, Spiro TE, Friedman RJ et al. Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin clinical trial group. J Bone Joint Surg Am 2001;83:336-45.
21. Manganelli D, Pazzagli M, Mazzantini D et al. Prolonged prophylaxis with unfractioned heparin is effective to reduce delayed deep vein thrombosis in total hip replacement. Respiration 1998;65:369-74.
22. Andersen BS. Postoperative activation of the haemostatic system–influence of prolonged thromboprophylaxis in patients undergoing total hip arthroplasty. Haemostasis 1997;27:219-27.
23. Dahl OE, Andreassen G, Aspelin T et al. Prolonged thromboprophylaxis following hip replacement surgery–results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (fragmin). Thromb Haemost 1997;77:26-31.
24. Nilsson PE, Bergqvist D, Benoni G et al. The post-discharge prophylactic management of the orthopedic patient with low-molecular-weight heparin: Enoxaparin. Orthopedics 1997;20:22-5.
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26. Planes A, Vochelle N, Darmon JY et al. Efficacy and safety of postdischarge administration of enoxaparin in the prevention of deep venous thrombosis after total hip replacement. A prospective randomised double-blind placebo-controlled trial. Drugs 1996;52 Suppl 7:47-54.
27. Bergqvist D, Benoni G, Björgell O et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996;335:696-700.
28. Kolb G, Bodamer I, Galster H et al. Reduction of venous thromboembolism following prolonged prophylaxis with the low molecular weight heparin certoparin after endoprothetic joint replacement or osteosynthesis of the lower limb in elderly patients. Thromb Haemost 2003;90:1100-5.
29. Ishida K, Shibanuma N, Kodato K et al. A prospective randomized comparative study to determine appropriate edoxaban administration period, to prevent deep vein thromboembolism in patients with total knee arthroplasty. J Orthop Sci 2018;23:1005-1010.
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