Abstract
Venous thromboembolism after total hip replacement or total knee replacement represents a significant complication of these surgical techniques, with profound clinical and economic consequences. As the detection of venous thromboembolism is particularly difficult in this setting, its prevention with thromboprophylactic agents is the most appropriate strategy. The anticoagulants currently used for thromboprophylaxis in orthopaedic surgery are injectable low-molecular-weight heparins (LMWHs) and oral coumarin derivatives such as warfarin. Orthopaedic surgery provides a good model with which to investigate the antithrombotic potential of novel agents, because of the relatively high venous thromboembolism event rates, and the opportunity to detect and quantify bleeding.
This paper provides an overview of the clinical burden of venous thromboembolism in orthopaedic surgery and the benefits and limitations of current thromboprophylactic modalities. In addition, geographical differences in treatment regimens regarding the choice of agent, timing of initiation and duration of thromboprophylaxis, and how these influence the incidence of venous thromboembolism, will be discussed.
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Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585–93
Heit JA, Melton LJ, Lohse CM, et al. Incidence of venous thromboembolism in hospitalized patients vs community residents. Mayo Clin Proc 2001; 76: 1102–10
Heit JA, Silverstein MD, Mohr DN, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch Intern Med 1999; 159: 445–53
Shapiro SS. Treating thrombosis in the 21st century. N Engl J Med 2003; 349: 1762–4
Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001; 119(1 Suppl.): 132S–75S
Dalen JE, Paraskos JA, Ockene IS, et al. Venous thromboembolism. Scope of the problem. Chest 1986; 89 (5 Suppl.): 370S–3S
Caprini JA, Arcelus JI, Maksimovic D, et al. Thrombosis prophylaxis in orthopedic surgery: current clinical considerations. J South Orthop Assoc 2002; 11: 190–6
Colwell CW Jr. Managing thromboembolic risk in hip and knee arthroplasty: state of the art. Orthopedics 2003; 26 (2 Suppl.): S231–6
Dahl OE, Aspelin T, Lyberg T. The role of bone traumatization in the initiation of proximal deep vein thrombosis during cemented hip replacement surgery in pigs. Blood Coagul Fibrinolysis 1995; 6: 709–17
Dahl OE, Molnar I, Vinje A, et al. Studies on coagulation, fibrinolysis, kallikrein—kinin and complement activation in systemic and pulmonary circulation during hip arthroplasty with acrylic cement. Thromb Res 1988; 50: 875–84
Dahl OE, Pedersen T, Kierulf P, et al. Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery. Thromb Res 1993; 70: 451–8
Prandoni P, Simioni P, Pagnan A. Treatment guidelines of acute venous thromboembolism. Current status and future perspectives [in Italian]. Minerva Cardioangiol 2003; 51: 361–71
Dahl OE, Aspelin T, Arnesen H, et al. Increased activation of coagulation and formation of late deep venous thrombosis following discontinuation of thromboprophylaxis after hip replacement surgery. Thromb Res 1995; 80: 299–306
Dahl OE, Westvik AB, Kierulf P, et al. Effect of monomethylmethacrylate on procoagulant activities of human monocytes and umbilical vein endothelial cells in vitro. Thromb Res 1994; 74: 377–87
Dahl OE, Garvik LJ, Lyberg T. Toxic effects of methyl-methacrylate monomer on leukocytes and endothelial cells in vitro. Acta Orthop Scand 1994; 65: 147–53
Francis CW, Pellegrini VD Jr, Marder VJ, et al. Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40. J Bone Joint Surg Am 1989; 71: 327–35
Høgevold HE, Høiseth A, Reikerås O. Deep vein thrombosis after total hip replacement. A venographic study. Acta Radiol 1990; 31: 571–3
Arnesen H, Dahl OE, Aspelin T, et al. Sustained prothrom-botic profile after hip replacement surgery: the influence of prolonged prophylaxis with dalteparin. J Thromb Haemost 2003; 1:971–5
Dahl OE, Andreassen G, Aspelin T, et al. Prolonged thromboprophylaxis following hip replacement surgery — results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin). Thromb Haemost 1997; 77: 26–31
White RH, Romano PS, Zhou H, et al. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998; 158: 1525–31
Dahl OE, Gudmundsen TE, Bjornara BT. Risk of clinical pulmonary embolism after joint surgery in patients receiving low-molecular-weight heparin prophylaxis in hospital: a 10-year prospective register of 3,954 patients. Acta Orthop Scand 2003; 3: 299–304
Warwick D, Williams MH, Bannister GC. Death and thromboembolic disease after total hip replacement. A series of 1162 cases with no routine chemical prophylaxis. J Bone Joint Surg Br 1995; 77: 6–10
Khaw FM, Moran CG, Pinder IM, et al. The incidence of fatal pulmonary embolism after knee replacement with no prophylactic anticoagulation. J Bone Joint Surg Br 1993; 75: 940–1
Anderson FA Jr, Hirsh J, White K, et al. Temporal trends in prevention of venous thromboembolism following primary total hip or knee arthroplasty 1996—2001: findings from the Hip and Knee Registry. Chest 2003; 124 (6 Suppl.): 349S–56S
Lie SA, Engesaeter LB, Havelin LI, et al. Early postoperative mortality after 67,548 total hip replacements: causes of death and thromboprophylaxis in 68 hospitals in Norway from 1987 to 1999. Acta Orthop Scand 2002; 73: 392–9
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
Brenkel IJ, Cook RE. Thromboprophylaxis in patients undergoing total hip replacement. Hosp Med 2003; 64: 281–7
Lausen IM, Rasmussen HM, Wille-Jorgensen PA. Prevention of postoperative thromboembolism in Denmark. A questionnaire study on principles of prevention of thrombosis at hospital surgery departments [in Danish]. Ugeskr Laeger 1992; 154: 3763–6
Walker N, Rodgers A, Gray H. Changing patterns of pharmacological thromboprophylaxis use by orthopaedic surgeons in New Zealand. Aust N Z J Surg 2002; 72: 335–8
Arnold DM, Kahn SR, Shrier I. Missed opportunities for prevention of venous thromboembolism: an evaluation of the use of thromboprophylaxis guidelines. Chest 2001; 120: 1964–71
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
Dahl O. Cardiorespiratory and vascular dysfunction related to major reconstructive orthopedic surgery. Acta Orthop Scand 1997; 68: 607–14
Agnelli G, Mancini GB, Biagini D. The rationale for long-term prophylaxis of venous thromboembolism. Orthopedics 2000; 23 (6 Suppl.): S643–6
Sikorski JM, Hampson WG, Staddon GE. The natural history and aetiology of deep vein thrombosis after total hip replacement. J Bone Joint Surg Br 1981; 63: 171–7
Lotke PA, Steinberg ME, Ecker ML. Significance of deep venous thrombosis in the lower extremity after total joint arthroplasty. Clin Orthop 1994; 299: 25–30
Hull RD, Pineo GF, Stein PD, et al. Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med 2001; 135: 858–69
Comp PC, Spiro TE, Friedman RJ, et al. Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am 2001; 83: 336–45
White RH, Henderson MC. Risk factors for venous thromboembolism after total hip and knee replacement surgery. Curr Opin Pulm Med 2002; 8: 365–71
CPMP, Committee for Proprietary Medicinal Products. Points to consider on clinical investigation of medicinal products for prophylaxis of intra- and post-operative venous thromboembolic risk. London, 29 June 2000 CPMP/EWP/707/98 (Available at: http://www.emea.eu.int/pdfs/human/ewp/070798en.pdf)
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Dahl, O.E. Orthopaedic Surgery as a Model for Drug Development in Thrombosis. Drugs 64 (Suppl 1), 17–25 (2004). https://doi.org/10.2165/00003495-200464001-00004
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DOI: https://doi.org/10.2165/00003495-200464001-00004