Thromb Haemost 1992; 67(04): 417-423
DOI: 10.1055/s-0038-1648463
Original Articles
Schattauer GmbH Stuttgart

Prevention of Deep Vein Thrombosis after Major Knee Surgery - A Randomized, Double-Blind Trial Comparing a Low Molecular Weight Heparin Fragment (Enoxaparin) to Placebo

Jacques R Leclerc
1   The Department of Medicine and Clinical Epidemiology Unit, Montreal General Hospital, McGill University, Montreal, Canada
,
William H Geerts
2   Department of Medicine and Clinical Epidemiology Unit, Sunnybrook Health Science Centre, University of Toronto, Toronto, Canada
,
Louis Desjardins
3   Division of Hematology, Centre Hospitalier de I’Université Laval, Université Laval, Quebec, Canada
,
François Jobin
4   Division of Hematology, Hopital du St-Sacrement, Université Laval, Quebec, Canada
,
François Laroche
5   Division of Radiology, Hôpital du St-Sacrement, Universite Laval, Quebec, Canada
,
Fernand Delorme
6   Department of Pathology, Universite de Montréal, Montreal, Canada
,
Sylvie Haviernick
7   Division of Clinical Research, Rhône-Poulenc Rorer, Montreal, Canada
,
Susan Atkinson
8   Division of Hematology, Montreal General Hôspital, Me Gill University, Montreal, Canada
,
Jean Bourgouine
9   Division of Pharmacology, Universite de Montreal, Montreal, Canada
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 07. Juni 1991

Accepted after revision 04. November 1991

Publikationsdatum:
03. Juli 2018 (online)

Summary

Consecutive patients undergoing knee arthroplasty or tibial osteotomy at four participating hospitals received either enoxaparin, 30 mg subcutaneously every 12 h (n = 66) or an identicalappearing placebo (n = 65). All study medications started the morning after the operation and were continued up to a maximum of 14 days. Patients underwent surveillance with 125I-fibrinogen leg scanning and impedance plethysmography. Bilateral contrast venography was performed routinely at Day 14 or at time of discharge, if sooner. Deep vein thrombosis was detected by venography in 35 of 54 patients (65%) in the placebo group and in 8 of 41 patients in the enoxaparin group (19%), a risk reduction of 71%, P <0.0001. For the entire study group, deep vein thrombosis was detected by either venography of non-invasive tests in 37 of 64 patients (58%) in the placebo group and in 11 of 65 patients (17%) in the enoxaparin group, a risk reduction of 71%, P <0.0001. Proximal vein thrombosis was found in 19% of the placebo patients and in none of the enoxaparin patients, a risk reduction of 100%, P <0.001. Bleeding complications occurred in 5 of 65 patients (8%) in the placebo group and in 4 of 66 patients (6%) in the enoxaparin group, P = 0.71. There were no differences in the amount of blood loss, minimum hemoglobin levels and number of units of packed red cells given between the two treatment groups. We conclude that a fixed dose regimen of enoxaparin, started post-operatively, is an effective and safe regimen for reducing the frequency of deep vein thrombosis after major knee surgery.

 
  • References

  • 1 National Institutes of Health Consensus Development Conference Statement: Prevention of venous thrombosis and pulmonary embolism. JAMA 1986; 256 (06) 744-749
  • 2 Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. N Engl J Med 1988; 318: 1162-1173
  • 3 Leyvraz PF, Richard J, Bachmann F, Van Melle G, Treyvaud JM, Livio JJ, Candarjis G. Adjusted versus fixed-dose subcutaneous heparin in the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med 1983; 309: 954-958
  • 4 Planes A, Vochelle N, Mazas F, Mansat C, Zucman J, Landais A, Pascariello JC, Weill D, Butel J. Prevention of postoperative venous thrombosis: A randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemostas 1988; >60 (03) 407-410
  • 5 Turpie AGG, Levine M, Hirsh J, Carter CJ, Jay RM, Powers PJ, Andrew M, Hull RD, Gent M. 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: 925-929
  • 6 Levine MN, Hirsh J, Gent M, Turpie AG, Leclerc JR, Powers PJ, Jay RM, Neemeh J. Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med 1991; 114: 545-551
  • 7 Francis CW, Marder VJ, McCollister E, Evarts McC. Two-step warfarin therapy. Prevention of postoperative venous thrombosis without excessive bleeding. JAMA 1983; 249: 374-378
  • 8 Hull R, Delmore TJ, Hirsh J, Gent M, Armstrong P, Lofthouse R, MacMillan A, Blackstone I, Reed-Davis R, Detwiler RC. Effectiveness of intermittent pulsatile elastic stockings for the prevention of calf and thigh vein thrombosis in patients undergoing elective knee surgery. Thromb Res 1979; 16: 37-45
  • 9 McKenna R, Galante J, Bachmann F, Wallace DL, Kaushal SP, Meredith P. Prevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression. Br Med J 1980; 280: 514-517
  • 10 Haas SB, Insall JN, Scuderi GR, Windsor RE, Ghelman B. Pneumatic sequential-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty. J Bone Jt Surg 1990; 72-A: 27-31
  • 11 Francis CW, Pellegrini VD, Stulberg BN, Miller ML, Totterman S, Marder VJ. Prevention of venous thrombosis after total knee arthroplasty. Comparison of antithrombin III and low-dose heparin with dextran. J Bone Jt Surg 1990; 72-A: 976-982
  • 12 Paiement GD, Wessinger SJ, Harris WH. Survey of prophylaxis against venous thromboembolism in adults undergoing hip surgery. Clin Orthopaed Related Res 1987; 223: 188-193
  • 13 Sutherland CJ, Schurman JR. Complications associated with warfarin prophylaxis in total knee arthroplasty. Clin Orthop 1987; 219: 158-162
  • 14 Carter CJ, Kelton JG, Hirsh J, Cerskus A, Santos AV, Gent M. The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982; 59: 1239-1245
  • 15 Ockelford PA, Carter CJ, Cerskus A, Smith CA, Hirsh J. Comparison of the in vivo hemorrhagic and antithrombotic effects of a low antithrombin III affinity heparin fraction. Thromb Res 1982; 27: 679-690
  • 16 Fernandez F, Nguyen P, Van Ryn J, Ofosu FA, Hirsh J, Buchanan M. Hemorrhagic doses of heparin and other glycosaminoglycans induce a platelet defect. Thromb Res 1986; 43: 491-496
  • 17 Salzman EW, Rosenberg RD, Smith MH, Lindon JN, Favreau L. Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 1980; 65: 64-73
  • 18 Lynch AF, Bourne RB, Rorabeck CH, Rankin RN, Donald A. Deep-vein thrombosis and continuous passive motion after total knee arthroplasty. J Bone Jt Surg 1988; 70-A: 11-14
  • 19 Ofosu FA, Leclerc JR, Delorme F, Craven S, Shafai L, Blajchman MA. The low molecular weight heparin enoxaparine inhibits the consumption of factor VII and prothrombin activation in vivo associated with elective knee replacement surgery (submitted for publication).
  • 20 Pavlov H, MacMoran JW, Funch RB, Bernhard RA, D’Orazio EA. Simplified outpatient lower extremity venography. Radiology 1978; 126: 525-527
  • 21 Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983; 249 (13) 1743-1745
  • 22 Gent M, Roberts RS. A meta-analysis of the studies of dihydroer-gotamine plus heparin in the prophylaxis of deep vein thrombosis. Chest 1986; 89: 396S-100S
  • 23 Cohen SH, Ehrlich GE, Kauffman MS, Cope C. Thrombophlebitis following knee surgery. J Bone Jt Surg 1973; 55-A: 106-112
  • 24 Lotke PA, Ecker ML, Alavi A, Berkowitz H. Indications for the treatment of deep venous thrombosis following total knee replacement. J Bone Jt Surg 1984; 66-A: 202-208
  • 25 Stulberg BN, Insall JN, Williams GW, Ghelman B. Deep-vein thrombosis following total knee replacement. J Bone Jt Surg 1984; 66-A: 194-201
  • 26 Stringer MD, Steadman CA, Hedges AR, Thomas EM, Morley TR, Kakkar W. Deep vein thrombosis after elective knee surgery. An incidence study in 312 patients. J Bone Jt Surg 1989; 71-B: 492-497
  • 27 Moser KM, LeMoine JR. Is embolic risk conditioned by location of deep venous thrombosis?. Ann Intern Med 1981; 94: 439-444
  • 28 Philbrick JT, Becker DM. Calf deep vein thrombosis. A wolf in sheep’s clothing?. Arch Intern Med 1988; 148: 2131-2138
  • 29 Hull RD, Delmore T, Genton E, Hirsh J, Gent M, Sackett D, McLoughlin D, Armstrong P. Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis. N Engl J Med 1979; 301: 855-858
  • 30 Hull RD, Hirsh J, Carter CJ, Jay RM, Ockelford PA, Buller HR, Turpie AG, Powers PJ, Kinch D, Dodd PE, Gill JG, Leclerc JR, Gent M. Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis. Ann Intern Med 1985; 102: 21-28
  • 31 Hull RD, Raskob GE, Hirsh J, Jay RM, Leclerc JR, Geerts WH, Rosenbloom D, Sackett D, Gent M. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-venous thrombosis. N Engl J Med 1986; 315: 1109-1114