Thromb Haemost 1996; 75(05): 706-711
DOI: 10.1055/s-0038-1650352
Original Article
Schattauer GmbH Stuttgart

Comparison of Two Warfarin Regimens in the Prevention of Venous Thrombosis following Total Knee Replacement

Charles W Francis
1   The Hematology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
,
Vincent D Pellegrini Jr.
5   The Department of Orthopaedics, Milton S. Hershey Medical Center, Hershey, PA, USA
,
Kristin M Leibert
1   The Hematology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
,
Saara Totterman
3   The Department of Radiology, University of Rochester School of Medicine and Dentistry, Rochester, NY
,
Michael V Azodo
3   The Department of Radiology, University of Rochester School of Medicine and Dentistry, Rochester, NY
,
Carl M Harris
2   The Department of Orthopaedic Surgery, University of Rochester School of Medicine and Dentistry, Rochester, NY
,
Christopher Cox
4   The Department of Biostatistics, University of Rochester School of Medicine and Dentistry, Rochester, NY
,
Victor J Marder
1   The Hematology Unit, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
› Author Affiliations
Further Information

Publication History

Received 25 August 1995

Accepted after revision 25 January 1996

Publication Date:
26 July 2018 (online)

Summary

A prospective, randomized trial was conducted to compare the effectiveness and safety of warfarin given in two regimens in prevention of venous thrombosis after total knee replacement. Adult patients scheduled for primary or revision total knee replacement were randomly assigned to receive either a “two-step” warfarin regimen beginning 10-14 days pre-operatively or, alternatively, to begin warfarin the night before surgery. Post-operatively, the dose was adjusted in both groups to achieve a target International Normalized Ratio (INR) of 2.2 and prophylaxis was continued until venography on post-operative days five through nine. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. The occurrence of deep vein thrombosis was nearly the same in the two treatment groups, 39% in patients randomized to the two-step regimen as compared to 38% in those beginning the night before surgery. The occurrence of proximal vein thrombosis was also similar, 5% versus 7% (p = NS). Patients in the two-step group received 1.33 ± 1.26 transfusions compared to 0.95 ± 1.22 in the night before group (p <0.05) and also had a lower nadir post-operative hematocrit of 26.7 ± 3.1 as compared to 28.5 ± 3.2 (p <0.0001). Major bleeding complications were associated with excessively prolonged INRs and occurred in five patients in the two-step group and two in the night before group. Patients in both groups who developed thrombosis had a significantly lower INR on post-operative days two and three compared to those without thrombosis. We conclude that a prophylactic warfarin regimen for prevention of deep vein thrombosis after total knee replacement beginning the night before surgery is more convenient and may be associated with less bleeding than a regimen beginning warfarin 10-14 days pre-operatively. Careful control of anticoagulant intensity is needed to achieve maximum effectiveness and avoidance of bleeding complications.

 
  • References

  • 1 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; 1: 514-517
  • 2 Stulberg BN, Insall JN, Williams GW, Ghelman B. Deep-vein thrombosis following total knee replacement. J Bone Joint Surg 1984; 66A: 194-201
  • 3 Vince KG, Kelly MA, Beck J, Insall JN. Continuous passive motion after total knee arthroplasty. J Arthroplasty 1987; 281-284
  • 4 Stringer MD, Steadman CA, Hedges AR, Thomas EM, Morley TR, Kakkar VV. Deep vein thrombosis after elective knee surgery. An incidence study in 312 patients. J Bone Joint Surg 1989; 7IB: 492-497
  • 5 Maynard MJ, Sculco TP, Ghelman B. Progression and regression of deep vein thrombosis after total knee arthroplasty. Clin Ortho Rel Res 1991; 273: 125-130
  • 6 Leclerc JR, Geerts WH, Desjardins L, Jobin F, Laroche F, Delorme F, Haviernick S, Atkinson S, Bourgouin J. 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 1992; 67: 417-423
  • 7 Wilson NV, Das SK, Kakkar VV, Maurice HD, Smibert JG, Thomas EM, Nixon JE. Thrombo-embolic prophylaxis in total knee replacement. Evaluation of the A-V impulse system. J Bone Joint Surg 1992; 74B: 50-52
  • 8 Lotke PA, Ecker ML, Alavi A, Berkowitz H. Indications for the treatment of deep venous thrombosis following total knee replacement. J Bone Joint Surg 1984; 66A: 202-208
  • 9 Lynch AF, Bourne RB, Rorabeck CH, Tankin RN, Donald A. Deep-vein thrombosis and continuous passive motion after total knee arthroplasty. J Bone Joint Surg 1988; 70A: 11-14
  • 10 Haas SB, Insall JN, Scuderi GR, Windsor RE, Ghelman B. Pneumatic sequen-tial-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty. J Bone Joint Surg 1990; 72A 27: 31
  • 11 Francis CW, Marder VJ, Evarts CM, Yaukoolbodi S. Two-step warfarin therapy. Prevention of postoperative venous thrombosis without excessive bleeding. JAMA 1983; 249: 374-378
  • 12 Hodge WA. Prevention of deep vein thrombosis after total knee arthroplasty. Coumadin versus pneumatic calf compression. Clin Ortho Rel Res 1991; 271: 101-105
  • 13 Kaempffe FA, Lifeso RM, Meinking C. Intermittent pneumatic compression versus coumadin. Prevention of deep vein thrombosis in lower-extremity total joint arthroplasty. Clin Ortho Rel Res 1991; 269: 89-97
  • 14 Hull R, Raskob G, Pineo G, Rosenbloom D, Evans W, Mallory T, Anquist K, Smith F, Hughes G, Green D, Elliott CG, Panju A, Brant R. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. New Engl J Med 1993; 329: 1370-1376
  • 15 RD Heparin Arthroplasty Group. RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. J Bone & Joint Surg 1994; 76: 1174-1185
  • 16 Francis CW, Pellegrini Jr VD, Stulberg BN, Miller ML, Totterman S, Marder VJ. Prevention of venous thrombosis after total knee arthroplasty. J Bone Joint Surg 1990; 72A: 976-982
  • 17 Leclerc JR, Geerts WH, Desjardins L, Jobin F, Laroche F, Delorme F, Haviernick S, Atkinson S, Bourgouin J. 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 1992; 67: 417-423
  • 18 Hull R, Delmore TJ, Hirsh J, Gent M, Armstrong P, Lofthouse R, MacMillan A, Blackstone I, Reed-Davis R, Detwiller 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
  • 19 Francis CW, Pellegrini Jr VD, Marder VJ, Totterman S, Harris CM, Gabriel KR, Azodo MV, Leibert KM. Comparison of warfarin and external pneumatic compression in prevention of venous thrombosis after total hip replacement. JAMA 1992; 267: 2911-2915
  • 20 Paiement G, Wessinger SJ, Waltman AC, Harris WH. Low-dose warfarin versus external pneumatic compression for prophylaxis against venous thromboembolism following total hip replacement. J Arthroplasty 1987; 2: 23-26
  • 21 NIH Consensus Conference: Prevention of venous thrombosis and pulmonary embolism. JAMA 1986; 256: 744-749
  • 22 Clagett P, Anderson FA, Levine MN, Salzman EW, Wheeler HB. Prevention of venous thromboembolism. Chest 1992; 102: 391S-407S
  • 23 Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989; 264: 4743-4746
  • 24 Conway EM, Bauer KA, Barzegar S, Rosenberg RD. Suppression of hemostatic system activation by oral anticoagulants in the blood of patients with thrombotic diatheses. J Clin Invest 1978; 80: 1535-1544
  • 25 De Weese JA, Rogoff SM. Phlebographic patterns of acute deep venous thrombosis of the leg. Surgery 1963; 53: 99-108
  • 26 Harris WH, Salzman EW, Athanasoulis C, Waltman AC, Baum S, De Sanctis RW. Comparison of warfarin, low-molecular-weight dextran, aspirin, and subcutaneous heparin in prevention of venous thromboembolism following total hip replacement. J Bone Joint Surg 1974; 56A: 1552-1562
  • 27 Scurr JH. How long after surgery does the risk of thromboembolism persist?. Acta Chir Scand 1990; (Suppl. 556) 22-24
  • 28 Bergqvist D. Long-term prophylaxis following orthopedic surgery. Haemostasis 1993; 23 (Suppl. 01) 27-31