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Major bleeding rates after prophylaxis against venous thromboembolism: Systematic review, meta-analysis, and cost implications

Published online by Cambridge University Press:  01 November 2004

James Muntz ,
David A Scott ,
Adam Lloyd  and
Matthias Egger
James Muntz
Affiliation:
Baylor College of Medicine
David A Scott
Affiliation:
Fourth Hurdle Consulting Ltd, London, UK
Adam Lloyd
Affiliation:
Fourth Hurdle Consulting Ltd, London, UK
Matthias Egger
Affiliation:
Universities of Bristol, Bristol, UK, and Bern, Switzerland
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Abstract

Objectives: The frequency and consequences of major bleeding associated with anticoagulant prophylaxis for prevention of venous thromboembolism is examined.

Methods: We conducted a systematic review and meta-analysis of controlled trials that reported rates of major bleeding after pharmaceutical thromboprophylaxis in patients undergoing major orthopedic surgery. Thromboprophylactic agents were divided into four groups:warfarin/other coumarin derivatives (WARF), unfractionated heparin (UFH), low molecular weight heparin (LMWH), and pentasaccharide (PS). Meta-analysis was conducted comparing LMWH with each of WARF, UFH, and PS. The frequency of re-operation due to major bleeding was reviewed and combined with published costs to estimate the mean cost of managing major bleeding events in these patients.

Results: Twenty-one studies including 20,523 patients met inclusion criteria for the meta-analysis. No evidence of significant between-trial heterogeneity in risk ratios was found. Combined (fixed effects) relative risks (RR) of major bleeding compared with LMWH were WARF – RR 0.59 (95 percent confidence interval [CI], 0.44–0.80); UFH – RR 1.52 (95 percent CI, 1.04–2.23); PS – RR 1.52 (95 percent CI, 1.11–2.09). Seventy-one studies including 32,433 patients were included in the review of consequences of major bleeding. We estimated that the average cost of major bleeding is $113 per patient receiving thromboprophylaxis.

Conclusions: LMWH results in fewer major bleeding episodes than UFH and PS but more than WARF. These events are costly and clinically important.

Keywords

Meta-analysisHemorrhageOrthopedicsThromboembolismCosts and cost analysis
Type
GENERAL ESSAYS
Information
International Journal of Technology Assessment in Health Care , Volume 20 , Issue 4 , November 2004 , pp. 405 - 414
Copyright
© 2004 Cambridge University Press

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References

Adolf J, Fritsche HM, Haas S, et al. 1999; Comparison of 3,000 IU aXa of the low molecular weight heparin certoparin with 5,000 IU aXa in prevention of deep vein thrombosis after total hip replacement. German Thrombosis Study Group. Int Angiol. 18: 122– 126.Google Scholar
Anderson DR, O'Brien B, et al. 1998. Economic evaluation comparing low molecular weight heparin with other modalities for the prevention of deep vein thrombosis and pulmonary embolism following total hip or knee arthroplasty. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA);
Anderson DR, O'Brien BJ, Levine MN, et al. 1993; Efficacy and cost of low-molecular-weight heparin compared with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty. Ann Intern Med. 119: 1105– 1112.Google Scholar
Anderson FAJ, White K. 2002; Prolonged prophylaxis in orthopedic surgery: Insights from the United States. Semin Thromb Hemost. 28: 43– 46.Google Scholar
Bauer KA, Eriksson BI, Lassen MR, et al. 2001; Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 345: 1305– 1310.Google Scholar
Begg CB, Mazumdar M. 1994; Operating characteristics of a rank correlation test for publication bias. Biometrics. 50: 1088– 1099.Google Scholar
Bergqvist D, Benoni G, Bjorgell O, et al. 1996; Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 335: 696– 700.Google Scholar
Borgstrom S, Greitz T, van der Linden W, Molin J, Rudics I. 1965; Anticoagulant prophylaxis of venous thrombosis in patients with fractured neck of the femur. A controlled clinical trial using venous phlebography. Acta Chir Scand. 129: 500– 508.Google Scholar
Brookenthal KR, Freedman KB, 2001; Lotke PA, Fitzgerald RH, Lonner JH. A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty. J Arthroplasty. 16: 293– 300.Google Scholar
Colwell CW, Berkowitz SD, Davidson BL, et al. 2001; Randomized, double-blind, comparison of Ximelagatran, an oral direct thrombin indicator, and enoxaparin to prevent venous thromboembolism (VTE) after total hip arthroplasty (THA). Presented to ASH, Orlando, December 7-11, 2001. Abstract 2952. Blood. 98.Google Scholar
Colwell CW, Collis DK, Paulson R, et al. 1999; Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am. 81: 932– 940.Google Scholar
Colwell CW, Spiro TE, Trowbridge AA, et al. 1994; Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am. 76: 3– 14.Google Scholar
Colwell CW, Spiro TE, Trowbridge AA, et al. 1995; Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep venous thrombosis after elective knee arthroplasty. Enoxaparin Clinical Trial Group. Clin Orthop. 321: 19– 27.Google Scholar
Comp PC, Spiro TE, Friedman RJ, et al. 2001; Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am. 83-A: 336– 345.Google Scholar
Comp PC, Voegeli T, McCutchen JW, et al. 1998; A comparison of danaparoid and warfarin for prophylaxis against deep vein thrombosis after total hip replacement: The Danaparoid Hip Arthroplasty Investigators Group. Orthopedics. 21: 1123– 1128.Google Scholar
Dahl OE, Andreassen G, Aspelin T, et al. 1997; Prolonged thromboprophylaxis following hip replacement surgery–results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin). Thromb Haemost. 77: 26– 31.Google Scholar
Deeks JJ, Altman DG, Bradburn MJ. 2001: Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis. In: Egger M, Davey Smith G, Altman DG, eds. Systematic reviews in health care: Meta-analysis in context. London: BMJ Publishing Group; 285– 312.
Egger M, Davey Smith G, Altman DG. 2001. Systematic reviews in health care: Meta-analysis in context. 2nd ed. London: BMJ Publishing Group;
Egger M, Davey Smith G, Schneider M, Minder CE. 1997; Bias in meta-analysis detected by a simple, graphical test. BMJ. 315: 629– 634.Google Scholar
Eriksson BI, Bauer KA, Lassen MR, et al. 2001; Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 345: 1298– 1304.Google Scholar
Eriksson BI, Ekman S, Lindbratt S, et al. 1997; Prevention of thromboembolism with use of recombinant hirudin. Results of a double-blind, multicenter trial comparing the efficacy of desirudin (Revasc) with that of unfractionated heparin in patients having a total hip replacement. J Bone Joint Surg Am. 79: 326– 333.Google Scholar
Eriksson BI, Wille-Jorgensen P, Kalebo P, et al. 1997; A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement. N Engl J Med. 337: 1329– 1335.Google Scholar
Eskeland G, Solheim K, Skjorten F. 1966; Anticoagulant prophylaxis, thromboembolism and mortality in elderly patients with hip fractures. A controlled clinical trial. Acta Chir Scand. 131: 16– 29.Google Scholar
Fauno P, Suomalainen O, Rehnberg V, et al. 1994; Prophylaxis for the prevention of venous thromboembolism after total knee arthroplasty. A comparison between unfractionated and low-molecular-weight heparin. J Bone Joint Surg Am. 76: 1814– 1818.Google Scholar
Fitzgerald RHJ, Spiro TE, Trowbridge AA, et al. 2001; Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin. J Bone Joint Surg Am. 83: 900– 906.Google Scholar
Fong YK, Ruban P, Yeo SJ, et al. 2000; Use of low molecular weight heparin for prevention of deep vein thrombosis in total knee arthroplasty–A study of its efficacy in an Asian population. Ann Acad Med Singapore. 29: 439– 441.Google Scholar
Francis CW, Davidson BL, Berkowitz SD, et al. 2001; Randomised, double-blind, comparative study of ximelagatran (pINN, formerly H 376/95), an oral direct thrombin inhibitor, and warfarin to prevent venous thromboembolism (VTE) after total knee arthroplasty (TKA). Presented to ISTH, July 6-12, 2001 Paris. Thromb Haemost. 86: OC44.Google Scholar
Francis CW, Marder VJ, Evarts CM, Yaukoolbodi S. 1983; Two-step warfarin therapy. Prevention of postoperative venous thrombosis without excessive bleeding. JAMA. 249: 374– 378.Google Scholar
Francis CW, Pellegrini VD, Leibert KM, et al. 1996; Comparison of two warfarin regimens in the prevention of venous thrombosis following total knee replacement. Thromb Haemost. 75: 706– 711.Google Scholar
Francis CW, Pellegrini VD, Totterman S, et al. 1997; Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin. J Bone Joint Surg Am. 79: 1365– 1372.Google Scholar
Freick H, Haas S. 1991; Prevention of deep vein thrombosis by low-molecular-weight heparin and dihydroergotamine in patients undergoing total hip replacement. Thromb Res. 63: 133– 143.Google Scholar
Friedman RJ, Dunsworth GA. 2000; Cost analyses of extended prophylaxis with enoxaparin after hip arthroplasty. Clin Orthop. 370: 171– 182.Google Scholar
Gallay S, Waddell JP, Cardella P, Morton J. 1997; A short course of low-molecular-weight heparin to prevent deep venous thrombosis after elective total hip replacement. Can J Surg. 40: 119– 123.Google Scholar
Gallus AS, Cade JF, Mills KW, Murphy W. 1992; Apparent lack of synergism between heparin and dihydroergotamine in prevention of deep vein thrombosis after elective hip replacement: A randomized trial reported in conjunction with an overview of previous results. Thromb Haemost. 68: 238– 244.Google Scholar
Geerts WH, Heit JA, Clagett GP, et al. 2001; Prevention of venous thromboembolism. Chest. 119: 132S– 175S.Google Scholar
Gent M, Hirsh J, Ginsberg JS, et al. 1996; Low-molecular-weight heparinoid Orgaran is more effective than aspirin in the prevention of venous thromboembolism after surgery for hip fracture. Circulation. 93: 80– 84.Google Scholar
Gerhart TN, Yett HS, Robertson LK, et al. 1991; Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial. J Bone Joint Surg Am. 73: 494– 502.Google Scholar
Gross M, Anderson DR, Nagpal S, O'Brien B. 1999; Venous thromboembolism prophylaxis after total hip or knee arthroplasty: A survey of Canadian orthopedic surgeons. Can J Surg. 42: 457– 461.Google Scholar
Haas S, Fareed J, Breyer HG, et al. 2001; Prevention of severe venous thromboembolism after hip and knee replacement surgery—A randomized comparison of low-molecular weight heparin with unfractionated heparin. Presented to ASH, December 7-11, 2001. Orlando. Abstract 2957. Blood. 98.Google Scholar
Hamilton HW, Crawford JS, Gardinier JH, Wiley AM. 1970; Venous thrombosis in patients with fracture of the upper end of the femur. J Bone Joint Surg Br. 52: 268– 289.Google Scholar
Hampson WG, Harris FC, Lucas HK, et al. 1974; Failure of low-dose heparin to prevent deep-vein thrombosis after hip-replacement arthroplasty. Lancet. 2: 795– 797.Google Scholar
Hamulyak K, Lensing AW, van der Meer J, et al. 1995; Subcutaneous low-molecular weight heparin or oral anticoagulants for the prevention of deep-vein thrombosis in elective hip and knee replacement? Fraxiparine Oral Anticoagulant Study Group. Thromb Haemost. 74: 1428– 1431.Google Scholar
Harris WH, Salzman EW, DeSanctis RW. 1967; The prevention of thromboembolic disease by prophylactic anticoagulation. A controlled study in elective hip surgery. J Bone Joint Surg Am. 49: 81– 89.Google Scholar
Hawkins DW, Langley PC, Krueger KP. 1998; A pharmacoeconomic assessment of enoxaparin and warfarin as prophylaxis for deep vein thrombosis in patients undergoing knee replacement surgery. Clin Ther. 20: 182– 195.Google Scholar
Hoek JA, Nurmohamed MT, Hamelynck KJ, et al. 1992; Prevention of deep vein thrombosis following total hip replacement by low molecular weight heparinoid. Thromb Haemost. 67: 28– 32.Google Scholar
Hull R, Hirsch J, Jay R. 1982; Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med. 307: 1676– 1681.Google Scholar
Hull R, Pineo G. 2001; A synthetic pentasaccharide for the prevention of deep-vein thrombosis. N Engl J Med. 345: 291.Google Scholar
Hull R, Raskob G, Pineo G, et al. 1993; A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med. 329: 1370– 1376.Google Scholar
Hull RD, Pineo GE, Raskob GE, et al. 1998; The economic impact of treating deep vein thrombosis with low molecular weight heparin: Outcome of therapy and health economics aspects. Haemostasis. 28: 8– 16.Google Scholar
Hull RD, Pineo GF, Francis C, et al. 2000; 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. 160: 2208– 2215.Google Scholar
Hull RD, Pineo GF, Francis C, et al. 2000; Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: A double-blind, randomized comparison. The North American Fragmin Trial Investigators. Arch Intern Med. 160: 2199– 2207.Google Scholar
Hull RD, Raskob GE, Pineo GF, et al. 1997; Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation. An economic perspective. Arch Intern Med. 157: 298– 303.Google Scholar
Jorgensen LN, Wille-Jorgensen P, Hauch O. 1993; Prophylaxis of postoperative thromboembolism with low molecular weight heparins. Br J Surg. 80: 689– 704.Google Scholar
Josefsson G, Dahlqvist A, Bodfors B. 1987; Prevention of thromboembolism in total hip replacement. Aspirin versus dihydroergotamine-heparin. Acta Orthop Scand. 58: 626– 629.Google Scholar
Kakkar VV, Howes J, Sharma V, Kadziola Z. 2000; A comparative double-blind, randomised trial of a new second generation LMWH (bemiparin) and UFH in the prevention of post-operative venous thromboembolism. The Bemiparin Assessment group. Thromb Haemost. 83: 523– 529.Google Scholar
Koch A, Bouges S, Ziegler S, et al. 1997; Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: Update of previous meta-analyses. Br J Surg. 84: 750– 759.Google Scholar
Lassen MR, Bauer KA, Eriksson BI, et al. 2002; Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: A randomised double-blind comparison. Lancet. 359: 1715– 1720.Google Scholar
Lassen MR, Borris LC, Anderson BS, et al. 1998; 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. 89: 281– 287.Google Scholar
Lassen MR, Borris LC, Christiansen HM, et al. 1988; Heparin/dihydroergotamine for venous thrombosis prophylaxis: Comparison of low-dose heparin and low molecular weight heparin in hip surgery. Br J Surg. 75: 686– 689.Google Scholar
Leclerc JR, Geerts WH, Desjardins L, et al. 1992; Prevention of deep vein thrombosis after major knee surgery–a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost. 67: 417– 423.Google Scholar
Leclerc JR, Geerts WH, Desjardins L, et al. 1996; Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med. 124: 619– 626.Google Scholar
Levine MN, Gent M, Hirsh J, et al. 1996; Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery. Arch Intern Med. 156: 851– 856.Google Scholar
Levine MN, Hirsh J, Gent M, et al. 1991; Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med. 114: 545– 551.Google Scholar
Levine MN, Raskob G, Landefeld S, Kearon C. 2001; Hemorrhagic complications of anticoagulant treatment. Chest. 119: 108S– 121S.Google Scholar
Leyvraz P, Bachmann F, Bohnet J, et al. 1992; Thromboembolic prophylaxis in total hip replacement: A comparison between the low molecular weight heparinoid Lomoparan and heparin-dihydroergotamine. Br J Surg. 79: 911– 914.Google Scholar
Leyvraz PF, Bachmann F, Hoek J, et al. 1991; Prevention of deep vein thrombosis after hip replacement: Randomised comparison between unfractionated heparin and low molecular weight heparin. BMJ. 303: 543– 548.Google Scholar
Mamdani MM, Weingarten CM, Stevenson JG. 1996; Thromboembolic prophylaxis in moderate-risk patients undergoing elective abdominal surgery: Decision and cost-effective analyses. Pharmacotherapy. 16: 1111– 1127.Google Scholar
Manganelli D, Pazzagli M, Mazzantini D, et al. 1998; Prolonged prophylaxis with unfractioned heparin is effective to reduce delayed deep vein thrombosis in total hip replacement. Respiration. 65: 369– 374.Google Scholar
Mannucci PM, Citterio LE, Panajotopoulos N. 1976; Low-dose heparin and deep-vein thrombosis after total hip replacement. Thromb Haemost. 36: 157– 164.Google Scholar
Marchetti M, Pistorio A, Barone M, Serafini S, Barosi G. 2001; Low-molecular weight heparin versus warfarin for secondary prophylaxis of venous thromboembolism: A cost-effectiveness analysis. Am J Med. 111: 130– 139.Google Scholar
Matzsch T, Bergqvist D, Fredin H, et al. 1991; Comparison of the thromboprophylactic effect of low molecular weight heparin versus dextran in total hip replacement. Thromb Haemorrh Dis. 3: 25– 29.Google Scholar
Moher D, Cook DJ, Jadad AR, et al. 1999; Assessing the quality of reports of randomised trials: Implications for the conduct of meta-analyses. Health Technol Assess. 3: 1– 98.Google Scholar
Morris GK, Mitchell JRA. 1976; Warfarin sodium in prevention of deep venous thrombosis and pulmonary embolism in patients with fractured neck of femur. Lancet. 2: 869– 873.Google Scholar
2001. NHS Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD guidelines for those carrying out of commissioning reviews. CRD Report No. 4. 2nd ed. York: NHS CRD.
Nurmohamed MT, Rosendaal FR, Buller HR, et al. 1992; Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: A meta-analysis. Lancet. 340: 152– 156.Google Scholar
Oertli D, Hess P, Durig M, et al. 1992; Prevention of deep vein thrombosis in patients with hip fractures: Low molecular weight heparin versus dextran. World J Surg. 16: 980– 984.Google Scholar
Paiement GD, Wessinger SJ, Harris WH. 1991; Cost-effectiveness of prophylaxis in total hip replacement. Am J Surg. 161: 519– 524.Google Scholar
Paiement GD, Wessinger SJ, Waltman AC, Harris WH. 1987; Low-dose warfarin versus external pneumatic compression for prophylaxis against venous thromboembolism following total hip replacement. J Arthroplasty. 2: 23– 26.Google Scholar
Palmer AJ, Koppenhagen K, Kirchhof B, et al. 1997; Efficacy and safety of low molecular weight heparin, unfractionated heparin, and warfarin for thrombo-embolism prophylaxis in orthopaedic surgery: A meta-analysis of randomised clinical trials. Haemostasis. 27: 75– 84.Google Scholar
Planes A, Samama MM, Lensing AW, et al. 1999; Prevention of deep vein thrombosis after hip replacement–comparison between two low-molecular heparins, tinzaparin and enoxaparin. Thromb Haemost. 81: 22– 25.Google Scholar
Planes A, Vochelle N, Darmon JY, et al. 1996; 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. 52: 47– 54.Google Scholar
Planes A, Vochelle N, Fagola M, Bellaud M. 1998; Comparison of two low-molecular-weight heparins for the prevention of postoperative venous thromboembolism after elective hip surgery. Reviparin Study Group. Blood Coagul Fibrinolysis. 9: 499– 505.Google Scholar
Planes A, Vochelle N, Fagola M, et al. 1991; Prevention of deep vein thrombosis after total hip replacement. The effect of low-molecular-weight heparin with spinal and general anaesthesia. J Bone Joint Surg Br. 73: 418– 422.Google Scholar
Planes A, Vochelle N, Mazas F, et al. 1988; Prevention of postoperative venous thrombosis: A randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost. 60: 407– 410.Google Scholar
Powers PJ, Gent M, Jay RM, et al. 1989; A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip. Arch Intern Med. 149: 771– 774.Google Scholar
Samama CM, Clergue F, Barre J, et al. 1997; Low molecular weight heparin associated with spinal anaesthesia and gradual compression stockings in total hip replacement surgery. Arar Study Group. Br J Anaesth. 78: 660– 665.Google Scholar
Schondorf TH, Hey D. 1976; Combined administration of low dose heparin and aspirin as prophylaxis of deep vein thrombosis after hip joint surgery. Haemostasis. 5: 250– 257.Google Scholar
Schulz KF, Chalmers I, Haynes RJ, Altman DG. 1995; Empirical evidence of bias: Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 273: 408– 412.Google Scholar
Sevitt S, Gallagher NG. 1959; Prevention of venous thrombosis and pulmonary embolism in injured patients: A trial of anticoagulation prophylaxis with phenindione in middle-aged and elderly patients with fractured necks of femur. Lancet. 2: 981– 989.Google Scholar
Shaieb MD, Watson BN, Atkinson RE. 1999; Bleeding complications with enoxaparin for deep venous thrombosis prophylaxis. J Arthroplasty. 14: 432– 438.Google Scholar
Shorr AF, Ramage AS. 2001; Enoxaparin for thromboprophylaxis after major trauma: Potential cost implications. Crit Care Med. 29: 1659– 1665.Google Scholar
Song F. 2002; Exploring heterogeneity in meta-analysis: Is the L'Abbe Plot useful? J Clin Epidemiol. 52: 725– 730.Google Scholar
Spiro TE, Johnson GJ, Christie MJ, et al. 1994; Efficacy and safety of enoxaparin to prevent deep venous thrombosis after hip replacement surgery. Enoxaparin Clinical Trial Group. Ann Intern Med. 121: 81– 89.Google Scholar
Stulberg BN, Francis CW, Pellegrini VD, et al. 1989; Antithrombin III/low-dose heparin in the prevention of deep-vein thrombosis after total knee arthroplasty. A preliminary report. Clin Orthop Relat Res. 248: 152– 157.Google Scholar
1991; The Danish Enoxaparin Study Group. Low molecular weight heparin (Enoxaparin) versus dextran 70 in the prevention of postoperative deep vein thrombosis after total hip replacement. Arch Intern Med. 151: 1621– 1624.
1992; The German Hip Arthroplasty Trial (GHAT) Group. Prevention of deep vein thrombosis with low molecular-weight heparin in patients undergoing total hip replacement: A randomized trial. Arch Orthop Trauma Surg. 111: 110– 120.
1999; The TIFDED Study Group. Thromboprophylaxis in hip fracture surgery: A pilot study comparing danaparoid, enoxaparin and dalteparin. The TIFDED Study Group. Haemostasis. 29: 310– 317.
Turpie AG. 1991; Efficacy of a postoperative regimen of enoxaparin in deep vein thrombosis prophylaxis. Am J Surg. 161: 532– 536.Google Scholar
Turpie AGG, Bauer KA, Eriksson BI, et al. 2002; Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: A randomised double-blind trial. Lancet. 359: 1726.Google Scholar
Turpie AGG, Bauer KA, Eriksson BI, et al. 2002; Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: A meta-analysis of 4 randomised double-blind studies. Arch Intern Med. 162: 1833– 1840.Google Scholar
Wilson MG, Pei LF, Malone KM, et al. 1994; Fixed low-dose versus adjusted higher-dose warfarin following orthopedic surgery. A randomized prospective trial. J Arthroplasty. 9: 127– 130.Google Scholar