Current Concepts Review   |    
Prevention of Venous Thromboembolic Disease After Total Hip and Knee Arthroplasty
Jay R. Lieberman, MD1; Wellington K. Hsu, MD1
1 Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California at Los Angeles, Center for Health Sciences 76-134, 10833 Le Conte Avenue, Los Angeles, CA 90095. E-mail address for J.R. Lieberman: jlieberman@mednet.ucla.edu. E-mail address for W.K. Hsu: whsu@mednet.ucla.edu
View Disclosures and Other Information
The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2005 Sep 01;87(9):2097-2112. doi: 10.2106/JBJS.D.03033
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Patients undergoing total hip and knee arthroplasty are at increased risk for the development of venous thromboembolic disease, and there is general agreement that these patients require prophylaxis.

The selection of a prophylactic agent involves a balance between efficacy and safety and often needs to be individualized for specific patients and institutions.

Despite extensive research, the ideal agent for prophylaxis against deep venous thrombosis has not been identified. The results of randomized trials indicate that low-molecular-weight heparin, warfarin, and fondaparinux are the most effective prophylactic agents after total hip arthroplasty and that low-molecular-weight heparin, warfarin, fondaparinux, and pneumatic compression boots are the most effective agents after total knee arthroplasty.

The duration of prophylaxis against deep venous thrombosis after total hip and knee arthroplasty remains controversial. Prophylaxis should be continued beyond hospital discharge. In the future, the determination of the duration of prophylaxis will be based on the risk stratification of individual patients.

The practice of discharging patients from the hospital without prophylaxis, even when the decision is based on negative results of procedures that screen for the presence of deep venous thrombosis, is not cost-effective.

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    David Bergqvist, M.D., Ph.D., FRCS
    Posted on December 08, 2005
    Prevention of VTE after major orthopaedic surgery and the role of prolonged prophylaxis
    Dept. of Surgical Sciences, Uppsala University Hospital, SWEDEN

    To The Editor:

    When writing history, including medical history, it would seem of some importance to be as correct as possible. After reading the review article by Lieberman, et al on prevention of thrombo-embolism after total hip or knee arthroplasty, I should like to provide some additional historical perspective.

    The inspiration to evaluate the efficacy of extended duration of prophylaxis was based on two observations: the occurrence of late fatal pulmonary embolism after surgery (1); and the occurrence of post hospital discharge deep vein thrombosis after major abdominal surgery (2). These observations formed the background to design studies to evaluate the possible role of prolonged prophylaxis, and elective hip surgery was considered a relevant experimental clinical model because it represents a fairly standardized surgical trauma event with a high frequency of thrombosis.

    The first such studies were published in 1996 (3, 4), and preceeded the study by White, et al (5). They verified the presence of late venous thromboembolism following arthroplasty and showed a reduction in venographically detected deep vein thrombosis when prophylaxis with molecular weight heparin was extended to approximately one month. Later many studies have confirmed these results (6-9).

    Lieberman and Hsu cite two studies by Planes, et al (4,10)(their references nos. 92 and 120), but the best summaries are found in two meta-analyses which were made in parallel and published the same year (11, 12). Lieberman and Hsu only refer to one of them (12). The value of prolonged prophylaxis was later confirmed by Prandoni, et al (13) and Samama, et al (14).

    Several of the studies listed by Lieberman and Hsu to support the use of prolonged prophylaxis have nothing to do with prolonged prophylaxis. Turpie, et al (15) compared placebo with enoxaparin for 14 days; Warwick (16) compared enoxaparin with control for three days; Kalodiki (17) compared control, enoxaparin and enoxaparin combined with stockings for 8-12 days; and Leclerc (18),evaluated the use of enoxaparin for a mean of 9 days.

    A major problem that Lieberman and Hsu correctly raise is that symptomatic venous thromboembolism was not assessed in the majority of studies. However, we (3) reported a significant reduction in this complication, and Hull et al (11) found significant reductions in clinical VTE.


    1. Bergqvist D, Lindblad B. A 30-year survey of pulmonary embolism verified at autopsy: an analysis of 1274 surgical patients. Br J Surg 1985;72(2):105-8.

    2. Scurr JH, Coleridge-Smith PD, Hasty JH. Deep venous thrombosis: a continuing problem. Bmj 1988;297(6640):28.

    3. Bergqvist D, Benoni G, Bjorgell O, et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement [see comments]. N Engl J Med 1996;335(10):696-700.

    4. Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet 1996;348(9022):224-8.

    5. White RH, Romano PS, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998;158(14):1525-31.

    6. 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) [see comments]. Thromb Haemost 1997;77(1):26-31.

    7. Lassen MR, Borris LC, Anderson BS, et al. Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study. Thromb Res 1998;89(6):281-7.

    8. 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(14):2208-15.

    9. 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-A(3):336-45.

    10. 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.

    11. Hull RD, Pineo GF, Stein PD, et al. Extended out-of-hospital low- molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med 2001;135(10):858-69.

    12. Eikelboom JW, Quinlan DJ, Douketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta -analysis of the randomised trials. Lancet 2001;358(9275):9-15.

    13. Prandoni P, Bruchi O, Sabbion P, et al. Prolonged thromboprophylaxis with oral anticoagulants after total hip arthroplasty: a prospective controlled randomized study. Arch Intern Med 2002;162(17):1966-71.

    14. Samama CM, Vray M, Barre J, et al. Extended venous thromboembolism prophylaxis after total hip replacement: a comparison of low-molecular- weight heparin with oral anticoagulant. Arch Intern Med 2002;162(19):2191- 6.

    15. Turpie A, Levine M, Hirsh J, et al. A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986;315(15):925 -9.

    16. Warwick D, Bannister GC, Glew D, et al. Perioperative low-molecular- weight heparin. Is it effective and safe. J Bone Joint Surg Br 1995;77(5):715-9.

    17. Kalodiki EP, Hoppensteadt DA, Nicolaides AN, et al. Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement. A randomised controlled trial. Int Angiol 1996;15(2):162-8.

    18. Leclerc JR, Gent M, Hirsh J, Geerts WH, Ginsberg JS. The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study of patients who underwent hip or knee arthroplasty. Canadian Collaborative Group. Arch Intern Med 1998;158(8):873-8.

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