Warfarin prophylaxis and venous thromboembolism in the first 5 days following hip and knee arthroplasty

Summary

Many orthopaedic surgeons use warfarin to prevent venous thromboembolism (VTE) following hip or knee arthroplasty. Since warfarin’s antithrombotic effects are delayed, we hypothesized that early VTE (occurring within 5 days post-operatively) would be more common in arthroplasty patients receiving warfarin monotherapy compared to those receiving enoxaparin. We performed a secondary analysis of a case-control study examining risk factors for post-operative thrombosis in postmenopausal women. We defined cases as patients who were diagnosed with thrombosis within 5 days of surgery. Controls without thrombosis were matched with cases by age, surgeon, year of surgery and surgical joint. 84 women with early post-operative thrombosis (cases) were matched with 206 controls. 18 cases (21.4%) had been prescribed warfarin monotherapy, compared with 7 controls (3.4%). 58 (69.1%) cases and 195 (94.7%) controls had been prescribed subcutaneous enoxaparin 30 mg twice daily, starting 12-24 hours after surgery. The odds ratio for any early thrombosis in patients receiving warfarin as opposed to enoxaparin 30 mg twice daily was 8.6 (p<0.0001). For proximal thrombosis, the odds ratio was 11.3 (p<0.0001). Multivariate analysis did not alter these findings. Warfarin’s delayed antithrombotic effects may not provide adequateVTE prophylaxis in the immediate post-operative setting. We suggest caution in employing warfarin monotherapy following joint arthroplasty.

Keywords

Warfarin - enoxaparin - arthroplasty - venous thromboembolism - post-operative

• References

• 1 Morris BA, Colwell CW, Hardwick ME. The use of low molecular weight heparins in the prevention of venous thromboembolic disease. Orthop Nurs 1998; 17: 23-9 77; quiz 30-1..
• 2 Geerts WH, Heit JA, Clagett GP. et al. Prevention of venous thromboembolism. Chest 2001; 119: 132S-175S.
• 3 Heit JA, Berkowitz SD, Bona R. et al. Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for the prevention of venous thromboembolism after total knee replacement surgery: a doubleblind, dose-ranging study. Ardeparin Arthroplasty Study Group. Thromb Haemost 1997; 77: 32-8.
• 4 Gross M, Anderson DR, Nagpal S. et al. Venous thromboembolism prophylaxis after total hip or knee arthroplasty: a survey of Canadian orthopedic surgeons. Can J Surg 1999; 42: 457-61.
• 5 Janku GV, Paiement GD, Green HD. Prevention of venous thromboembolism in orthopaedics in the United States. Clin Orthop 1996; 313-21.
• 6 Fossler MJ, Barrett JS, Hainer JW. et al. Pharmacodynamics of intravenous and subcutaneous tinzaparin and heparin in healthy volunteers. Am J Health Syst Pharm 2001; 58: 1614-21.
• 7 Esmon CT, Vigano-D’Angelo S, D’Angelo A. et al. Anticoagulation proteins C and S. Adv Exp Med Biol 1987; 214: 47-54.
• 8 Hull R, Raskob G, Pineo G. et al. 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 1993; 329: 1370-6.
• 9 Francis CW, Pellegrini Jr. VD, Totterman S. et al. Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin. J Bone Joint Surg Am 1997; 79: 1365-72.
• 10 Freedman KB, Brookenthal KR, Fitzgerald Jr. RH. et al. A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg Am 2000; 82-A: 929-38.
• 11 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 Am 1994; 76: 1174-85.
• 12 Hull RD, Raskob GE, Pineo GF. et al. Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation. An economic perspective. Arch Intern Med 1997; 157: 298-303.
• 13 Stern SH, Wixson RL, O’Connor D. Evaluation of the safety and efficacy of enoxaparin and warfarin for prevention of deep vein thrombosis after total knee arthroplasty. J Arthroplasty 2000; 15: 153-8.
• 14 Francis CW, Berkowitz SD, Comp PC. et al. Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med 2003; 349: 1703-12.
• 15 Comp PC, Voegeli T, McCutchen JW. et al. A comparison of danaparoid and warfarin for prophylaxis against deep vein thrombosis after total hip replacement: The Danaparoid Hip Arthroplasty Investigators Group. Orthopedics 1998; 21: 1123-8.
• 16 Howard AW, Aaron SD. Low molecular weight heparin decreases proximal and distal deep venous thrombosis following total knee arthroplasty. A meta-analysis of randomized trials. Thromb Haemost 1998; 79: 902-6.
• 17 Hull RD, Pineo GF, MacIsaac S. Low-molecular-weight heparin prophylaxis: preoperative versus postoperative initiation in patients undergoing elective hip surgery. Thromb Res 2001; 101: V155-62.
• 18 Leclerc JR, Geerts WH, Desjardins L. et al. Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med 1996; 124: 619-26.
• 19 Hamulyak K, Lensing AW, van der Meer J. et al. 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 1995; 74: 1428-31.
• 20 Hull RD, Pineo GF, Stein PD. et al. Timing of initial administration of low-molecular-weight heparin prophylaxis against deep vein thrombosis in patients following elective hip arthroplasty: a systematic review. Arch Intern Med 2001; 161: 1952-60.
• 21 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: 1966-71.