Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Summary for Patients    Summary for Patients (PDF)    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Hull, R. D.    Raskob, G. E.    Related Articles in PubMed    PubMed Citation    PubMed

ARTICLE

Extended Out-of-Hospital Low-Molecular-Weight Heparin Prophylaxis against Deep Venous Thrombosis in Patients after Elective Hip Arthroplasty

A Systematic Review

Russell D. Hull, MBBS, MSc; Graham F. Pineo, MD; Paul D. Stein, MD; Andrew F. Mah, BSc; Susan M. MacIsaac, MSc; Ola E. Dahl, MD, PhD; Matthew Butcher, BSc; Rollin F. Brant, PhD; William A. Ghali, MD, MPH; David Bergqvist, MD, PhD; and Gary E. Raskob, PhD

20 November 2001 | Volume 135 Issue 10 | Pages 858-869

Purpose: Evidence-based medicine guidelines based on venographic end points recommend in-hospital prophylaxis with low-molecular-weight heparin (LMWH) in patients having elective hip surgery. Emerging data suggest that out-of-hospital use may offer additional protection; however, uncertainty remains about the risk–benefit ratio. To provide clinicians with a practical pathway for translating clinical research into practice, we systematically reviewed trials comparing extended out-of-hospital LMWH prophylaxis versus placebo.

Data Sources: Studies were identified by 1) searching PubMed, MEDLINE, and the Cochrane Library Database for reports published from January 1976 to May 2001; 2) reviewing references from retrieved articles; 3) scanning abstracts from conference proceedings; and 4) contacting pharmaceutical companies and investigators of the original reports.

Study Selection: Randomized, controlled trials comparing extended out-of-hospital prophylaxis with LMWH versus placebo in patients having elective hip arthroplasty.

Data Extraction: Two reviewers extracted data independently. Reviewers evaluated study quality by using a validated four-item instrument.

Data Synthesis: Six of seven original articles met the defined inclusion criteria. The included studies were double-blind trials that used proper randomization procedures. Compared with placebo, extended out-of-hospital prophylaxis decreased the frequency of all episodes of deep venous thrombosis (placebo rate, 150 of 666 patients [22.5%]; relative risk, 0.41 [95% CI, 0.32 to 0.54; P < 0.001]), proximal venous thrombosis (placebo rate, 76 of 678 patients [11.2%]; relative risk, 0.31 [CI, 0.20 to 0.47; P < 0.001]), and symptomatic venous thromboembolism (placebo rate, 36 of 862 patients [4.2%]; relative risk, 0.36 [CI, 0.20 to 0.67; P = 0.001]). Major bleeding was rare, occurring in only one patient in the placebo group.

Conclusions: Extended LMWH prophylaxis showed consistent effectiveness and safety in the trials (regardless of study variations in clinical practice and length of hospital stay) for venographic deep venous thrombosis and symptomatic venous thromboembolism. The aggregate findings support the need for extended out-of-hospital prophylaxis in patients undergoing hip arthroplasty surgery.

Author and Article Information

From University of Calgary, Calgary, Alberta, Canada; St. Joseph Mercy—Oakland, Detroit, Michigan; Ullevaal University Hospital, Oslo, Norway; Uppsala University, Uppsala, Sweden; and University of Oklahoma, Oklahoma City, Oklahoma.

Acknowledgments: The authors thank the following individuals for their assistance on this manuscript: Adrian Jorgenson, Rita Biel, Jill Ho-You, Vicki Stagg, Jennifer Ringrose, Derek Leung, and Mickey Correa.

Requests for Single Reprints: Russell D. Hull, MBBS, MSc, Thrombosis Research Unit, Foothills Hospital, Room 601 South Tower, 1403—29th Street NW, Calgary, Alberta T2N 2T9, Canada; e-mail, jeanne.sheldon{at}calgaryhealthregion.ca.

Current Author Addresses: Drs. Hull and Pineo, Mr. Mah, Ms. MacIsaac, Mr. Butcher: Thrombosis Research Unit, University of Calgary, Foothills Hospital, Room 601 South Tower, 1403- 29th Street NW, Calgary, T2N 2T9 Alberta, Canada.

Drs. Brant and Ghali: University of Calgary, Community Health Sciences, 3310 Hospital Drive NW, Calgary, T2N 2T9 Alberta, Canada.

Dr. Stein: Saint Joseph Mercy—Oakland, 888 Woodward Avenue, Suite 107, Pontiac, MI, 48341-2964.

Dr. Dahl: Lokenlia 36, 1352 Kolsas, Norway.

Dr. Bergqvist: Department of Surgery, Akademiska sjukhuset, Malmö General Hospital, S-75185 Uppsala, Sweden.

Dr. Raskob: Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Box 26901 (LIB 221), Oklahoma City, OK 73190.

Author Contributions: Conception and design: R.D. Hull, G.F. Pineo, A.F. Mah, O.E. Dahl.

Analysis and interpretation of the data: R.D. Hull, G.F. Pineo, A.F. Mah, S.M. MacIsaac, O.E. Dahl, M. Butcher, R.F. Brant, W.A. Ghali, D. Bergqvist, G.E. Raskob.

Drafting of the article: R.D. Hull, G.F. Pineo, P.D. Stein, A.F. Mah, S.M. MacIsaac, O.E. Dahl, R.F. Brant, G.E. Raskob.

Critical revision of the article for important intellectual content: R.D. Hull, G.F. Pineo, A.F. Mah, O.E. Dahl, M. Butcher, W.A. Ghali, D. Bergqvist, G.E. Raskob.

Final approval of the article: R.D. Hull, G.F. Pineo, A.F. Mah, O.E. Dahl, R.F. Brant, W.A. Ghali, D. Bergqvist, G.E. Raskob.

Provision of study materials or patients: G.F. Pineo.

Statistical expertise: R.D. Hull, W.A. Ghali, G.E. Raskob.

Obtaining of funding: G.F. Pineo.

Administrative, technical, or logistic support: M. Butcher.

Collection and assembly of data: G.F. Pineo, M. Butcher, D. Bergqvist.

Related articles in Annals:

Summaries for Patients
Low-Molecular-Weight Heparin Given for Several Weeks after Hip Surgery Prevents Deep Venous Thrombosis

Annals 2001 135: S55. [Full Text]  

Letters
Extended Out-of-Hospital Low-Molecular-Weight Heparin for Prophylaxis against Deep Venous Thrombosis
Naoko Murashige AND Roslyn F. Schneider

Annals 2002 137: 620-621. [Full Text]  

Letters
Extended Out-of-Hospital Low-Molecular-Weight Heparin for Prophylaxis against Deep Venous Thrombosis
Russell D. Hull, Graham F. Pineo, AND Andrew F. Mah

Annals 2002 137: 621. [Full Text]  

This article has been cited by other articles:

				A. F Shorr, E. A Nutescu, E. Farrelly, R. Horblyuk, L. E Happe, and M. Franklin Postdischarge Oral Versus Injectable Anticoagulation Following Major Orthopedic Surgery Ann. Pharmacother., September 1, 2008; 42(9): 1222 - 1228. [Abstract] [Full Text] [PDF]

				M. P. Gulseth, J. Michaud, and E. A. Nutescu Rivaroxaban: An oral direct inhibitor of factor Xa Am. J. Health Syst. Pharm., August 15, 2008; 65(16): 1520 - 1529. [Abstract] [Full Text] [PDF]

				B. I. Eriksson, L. C. Borris, R. J. Friedman, S. Haas, M. V. Huisman, A. K. Kakkar, T. J. Bandel, H. Beckmann, E. Muehlhofer, F. Misselwitz, et al. Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Hip Arthroplasty N. Engl. J. Med., June 26, 2008; 358(26): 2765 - 2775. [Abstract] [Full Text] [PDF]

				E. Rahme PhD, K. Dasgupta MD MSc, M. Burman MD, H. Yin PhD, S. Bernatsky MD PhD, G. Berry MD, H. Nedjar MSc, and S. R. Kahn MD MSc Postdischarge thromboprophylaxis and mortality risk after hip-or knee-replacement surgery Can. Med. Assoc. J., June 3, 2008; 178(12): 1545 - 1554. [Abstract] [Full Text] [PDF]

				W. H. Geerts, D. Bergqvist, G. F. Pineo, J. A. Heit, C. M. Samama, M. R. Lassen, and C. W. Colwell Prevention of Venous Thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 381S - 453S. [Abstract] [Full Text] [PDF]

				S. Vescia, A. K. Baumgartner, V. R. Jacobs, M. Kiechle-Bahat, A. Rody, S. Loibl, and N. Harbeck Management of venous port systems in oncology: a review of current evidence Ann. Onc., January 1, 2008; 19(1): 9 - 15. [Abstract] [Full Text] [PDF]

				F. J. Singelyn, C. C.P.M. Verheyen, F. Piovella, H. K. Van Aken, N. Rosencher, and for the EXPERT Study Investigators The Safety and Efficacy of Extended Thromboprophylaxis With Fondaparinux After Major Orthopedic Surgery of the Lower Limb With or Without a Neuraxial or Deep Peripheral Nerve Catheter: The EXPERT Study Anesth. Analg., December 1, 2007; 105(6): 1540 - 1547. [Abstract] [Full Text] [PDF]

				D. A. Garcia, M. A. Khamashta, and M. A. Crowther How we diagnose and treat thrombotic manifestations of the antiphospholipid syndrome: a case-based review Blood, November 1, 2007; 110(9): 3122 - 3127. [Abstract] [Full Text] [PDF]

				D. WARWICK Author's reply J Bone Joint Surg Br, October 1, 2007; 89-B(10): 1409 - 1410. [Full Text] [PDF]

				A. Leizorovicz and SMART Venography Study Steering Committee Epidemiology of post-operative venous thromboembolism in Asian patients. Results of the SMART venography study Haematologica, September 1, 2007; 92(9): 1194 - 1200. [Abstract] [Full Text] [PDF]

				D. Warwick, R. J. Friedman, G. Agnelli, E. Gil-Garay, K. Johnson, G. FitzGerald, and F. M. Turibio Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: FINDINGS FROM THE GLOBAL ORTHOPAEDIC REGISTRY J Bone Joint Surg Br, June 1, 2007; 89-B(6): 799 - 807. [Abstract] [Full Text] [PDF]

				C. Skedgel, R. Goeree, S. Pleasance, K. Thompson, B. O'Brien, and D. Anderson The Cost-Effectiveness of Extended-Duration Antithrombotic Prophylaxis After Total Hip Arthroplasty J. Bone Joint Surg. Am., April 1, 2007; 89(4): 819 - 828. [Abstract] [Full Text] [PDF]

				R. J. Friedman Optimal Duration of Prophylaxis for Venous Thromboembolism Following Total Hip Arthroplasty and Total Knee Arthroplasty J. Am. Acad. Ortho. Surg., March 1, 2007; 15(3): 148 - 155. [Abstract] [Full Text] [PDF]

				E. A Nutescu, A. K Wittkowsky, P. P Dobesh, D. W Hawkins, and W. E Dager Choosing the Appropriate Antithrombotic Agent for the Prevention and Treatment of VTE: A Case-Based Approach Ann. Pharmacother., September 1, 2006; 40(9): 1558 - 1570. [Abstract] [Full Text] [PDF]

				G. Piazza and S. Z. Goldhaber Acute Pulmonary Embolism: Part II: Treatment and Prophylaxis Circulation, July 18, 2006; 114(3): e42 - e47. [Full Text] [PDF]

				S. Motte, C. M. Samama, J. Guay, J. Barre, J.-Y. Borg, and N. Rosencher Prevention of postoperative venous thromboembolism. Risk assessment and methods of prophylaxis: [La prevention de la thromboembolie veineuse postoperatoire. Evaluation du risque et methodes de prophylaxie] Can J Anesth, June 1, 2006; 53(6_suppl): S68 - S79. [Abstract] [Full Text] [PDF]

				G. Thabut, C. Estellat, I. Boutron, C. M. Samama, and P. Ravaud Methodological issues in trials assessing primary prophylaxis of venous thrombo-embolism Eur. Heart J., January 2, 2006; 27(2): 227 - 236. [Abstract] [Full Text] [PDF]

				M. Levine and A.K. Kakkar Catheter-Associated Thrombosis: Thromboprophylaxis or Not? J. Clin. Oncol., June 20, 2005; 23(18): 4006 - 4008. [Full Text] [PDF]

				J. J Enyart and R. J Jones Low-Dose Warfarin for Prevention of Symptomatic Thromboembolism After Orthopedic Surgery Ann. Pharmacother., June 1, 2005; 39(6): 1002 - 1007. [Abstract] [Full Text] [PDF]

				M. McGuire and P. P. Dobesh Therapeutic Update on the Prevention and Treatment of Venous Thromboembolism Journal of Pharmacy Practice, October 1, 2004; 17(5): 289 - 307. [Abstract] [PDF]

				W. H. Geerts, G. F. Pineo, J. A. Heit, D. Bergqvist, M. R. Lassen, C. W. Colwell, and J. G. Ray Prevention of Venous Thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 338S - 400S. [Abstract] [Full Text] [PDF]

				T. Bombeli and D. R. Spahn Updates in perioperative coagulation: physiology and management of thromboembolism and haemorrhage Br. J. Anaesth., August 1, 2004; 93(2): 275 - 287. [Abstract] [Full Text] [PDF]

				S. R. Kahn and J. S. Ginsberg Relationship Between Deep Venous Thrombosis and the Postthrombotic Syndrome Arch Intern Med, January 12, 2004; 164(1): 17 - 26. [Abstract] [Full Text] [PDF]

				A. G. G. Turpie, B. I. Eriksson, K. A. Bauer, and M. R. Lassen New Pentasaccharides for the Prophylaxis of Venous Thromboembolism: Clinical Studies Chest, December 1, 2003; 124(6_suppl): 371S - 378S. [Abstract] [Full Text] [PDF]

				J.-F. Hardy and H. N. Lee Best evidence in anesthetic practice: Prevention: Fondaparinux is better than enoxaparin for prevention of major venous thromboembolism after orthopedic surgery Can J Anesth, October 1, 2003; 50(8): 764 - 766. [Full Text] [PDF]

				B. I. Eriksson and M. R. Lassen Duration of Prophylaxis Against Venous Thromboembolism With Fondaparinux After Hip Fracture Surgery: A Multicenter, Randomized, Placebo-Controlled, Double-blind Study Arch Intern Med, June 9, 2003; 163(11): 1337 - 1342. [Abstract] [Full Text] [PDF]

				M. O'Donnell, L.-A. Linkins, C. Kearon, J. Julian, and J. Hirsh Reduction of Out-of-Hospital Symptomatic Venous Thromboembolism by Extended Thromboprophylaxis With Low-Molecular-Weight Heparin Following Elective Hip Arthroplasty: A Systematic Review Arch Intern Med, June 9, 2003; 163(11): 1362 - 1366. [Abstract] [Full Text] [PDF]

				S. B Deitelzweig, G. J Vanscoy, C. S Niccolai, and T. L Rihn Venous Thromboembolism Prevention with LMWHs in Medical and Orthopedic Surgery Patients Ann. Pharmacother., March 1, 2003; 37(3): 402 - 411. [Abstract] [Full Text] [PDF]

				C. B. Phillips, J. A. Barrett, E. Losina, N. N. Mahomed, E. A. Lingard, E. Guadagnoli, J. A. Baron, W. H. Harris, R. Poss, and J. N. Katz Incidence Rates of Dislocation, Pulmonary Embolism, and Deep Infection During the First Six Months After Elective Total Hip Replacement J. Bone Joint Surg. Am., January 17, 2003; 85(1): 20 - 26. [Abstract] [Full Text] [PDF]

				N. Murashige and R. F. Schneider Extended Out-of-Hospital Low-Molecular-Weight Heparin for Prophylaxis against Deep Venous Thrombosis Ann Intern Med, October 1, 2002; 137(7): 620 - 621. [Full Text] [PDF]

				Additional articles abstracted in ACP Journal Club Evid. Based Med., July 1, 2002; 7(4): 99 - 99. [Full Text] [PDF]

				DVT Prophylaxis in Hip Arthroplasty Patients Should Continue After Hospital Discharge Journal Watch (General), November 30, 2001; 2001(1130): 2 - 2. [Full Text]