Prophylaxis of Venous Thromboembolism Following Orthopedic Surgery: Mechanical and Pharmacological Approaches and the Need for Extended Prophylaxis

Introduction

Major orthopedic surgery, particularly total joint replacement or hip fracture, represents a high risk of future development of postoperative venous thromboembolism and warrants the routine use of prophylaxis with either mechanical devices or pharmacological agents. The aim of prophylaxis is to prevent fatal pulmonary embolism (PE) and the morbidity of deep vein thrombosis (DVT), particularly the development of post-thrombotic syndrome. Patterns of clinical practice, with respect to the prevention of venous thromboembolism and the appropriate use of anticoagulants for the treatment of thrombotic disease, have been strongly influenced by recent consensus conferences.^1,2 Rules of evidence for assessing the literature have been applied to all recommendations regarding the prevention and treatment of thrombotic disease. These results were extrapolated using evidence gleaned from major clinical disorders and are based only on nonrandomized clinical trials or case series.^1-3 Data from a large number of Level I clinical trials in patients undergoing orthopedic surgery have provided answers to many of the questions regarding prophylaxis of venous thromboembolism. In this review, we will discuss the prevention of venous thromboembolism following orthopedic surgery and discuss some of the controversial issues where further studies are required.

• References

• 1 Clagett GP, Anderson FA, Geerts W, Heit JA, Knudson M, Lieberman JR, Merli GJ, Wheeler HB. Prevention of venous thromboembolism. Chest 1998; 114 (Suppl. 05) 531S-560S.
• 2 Nicolaides AN, Bergqvist D, Hull R. et al. Prevention of venous thromboembolism. International consensus statement. Int Angiol 1997; 16 (01) 3-38.
• 3 Guyatt GH, Cook DJ, Sackett DL, Eckman M, Pauker S. Grades of recommendation for antithrombotic agents. Chest 1998; 114: 441S-444S.
• 4 Imperiale TF, Speroff T. A meta-analysis of methods to prevent venous thromboembolism following total hip replacement. JAMA 1994; 271 (22) 1780-1785.
• 5 Collins R, Scrimgeour A, Yusef S. et al. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. N Engl J Med 1988; 318: 1162-1173.
• 6 Campling EA, Devlin HB, Hoile RW, Lynn JN. The Report of the National Confidential Enquiry into Perioperative Deaths. NCE POD London, UK, 1989-90. The Report of National Confidentiality Enquiry into Perioperative Deaths. London: National Confidentiality Enquiry into Perioperative Deaths; 1996
• 7 Murray DW, Britton AR, Bulstrode CJK. Thromboprophylaxis and death after total hip replacement. J Bone Joint Surg 1996; 78 (06) 863-870.
• 8 Warwick D, Williams MH, Bannister GC. Death and thromboembolisc disease after total hip replacement. J Bone Joint Surg Br 1995; 77: 6-10.
• 9 Planes A, Vochelle N, Darmon JY, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomized comparison of enoxaparin versus placebo. Lancet 1996; 348: 224-228.
• 10 Bergqvist D, Benoni G, Bjorgell O, Fredin H, Hedlundh U, Nicolas S, Nelsson P, Nylander G. Low molecular weight heparin (Enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996; 335 (10) 696-700.
• 11 Dahl OE, Andreassen G, Aspelin T, Muller C, Mathiesen P, Nyhus S, Abdelnoor M, Solhaug JH, Arnesen H. Prolonged thromboprophylaxis following hip replacement surgery: results of a double-blind prospective, randomized, placebo-controlled study with Dalteparin (fragmin). Thromb and Haemost 1997; 77 (01) 26-31.
• 12 Lassen MR, Borris LC, Anderson BS, Jensen HP, Skejo Bro HP, Andersen G, Petersen AO, Siem P, Horlyck E, Jensen BV, Thomsen PB, Hansen BR, Erin-Madsen J, Moller JC, Rotwitt L, Christensen F, Nielsen JB, Jorgensen PS, Paaske B, Torholm C, Hvidt P, Jensen NK, Nielsen AB, Appelquist E, Tjalve E. Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty - the Danis Prolonged Prophylaxis (DaPP) Study. Thromb Res 1998; 89 (06) 281-287.
• 13 Heit JA, Elliott CG, Trowbridge AA. et al. Extended out-ofhospital LMWH venous thromboembolism prophylaxis after total hip or knee replacement surgery. Blood 1998; 92 (10) 2060a.
• 14 Hull RD, Pineo GF. Pre-operative low-molecular-weight heparin (pre-op LMWH) versus post-op low-molecular-weight heparin (post-op LMWH) versus warfarin for the prevention of deep vein thrombosis (DVT) after total hip replacement (THR): in hospital and out-of-hospital prophylaxis. Eighth Annual Fall Meeting of the American Association of Hip and Knee Surgeons. Abstract #7 1998
• 15 Clagett GP, Anderson Jr FA, Geerts W, Heit JA, Knudson M, Lieberman JR, Merli GJ, Wheeler HB. Prevention of Venous Thromboembolism. Chest 1998; 114 (05) 531s-560s.
• 16 Robinson KS, Anderson DR, Gross M, Petrie D, Leighton R, Stanish W, Alexander D, Mitchell M, Flemming B, Gent M. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the Post-Arthroplasty Screening Study. Ann Intern Med 1997; 127: 439-445.
• 17 Leclerc JB, Gent M, Hirsh J, Geerts WH, Ginsberg JS. The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study in patients who underwent hip or knee arthroplasty. Arch Intern Med 1998; 158: 873-878.
• 18 Haake DA, Berkman SA. Venous thromboembolic disease after hip surgery. Clin Orthop 1989; 242-212.
• 19 Eskeland G, Solheim K, Skhorten F. Anticoagulant prophylaxis, thromboembolism and mortality in elderly patients with hip fracture: a controlled clinical trial. Acta Chir Scand 1986; 131: 16-29.
• 20 Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of antiplatelet therapy - III: reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Br Med J 1994; 308: 235-246.
• 21 MacMahon S, Rodgers A, Collins R, Farrell B. Antiplatelet therapy to prevent thrombosis after hip fracture: rationale for a randomised trial. J Bone Joint Surg Br 1994; 76-B: 521-524.
• 22 Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994; 331: 1601-1606.
• 23 Abelseth G, Buckley RE, Pineo GF, Hull R, Rose MS. Incidence of deep-vein thrombosis in patients with fractures of the lower extremity dital to the hip. J Orthop Trauma 1996; 10: 230-235.
• 24 Demers C, Marcoux S, Ginsberg JS, Laroche F, Cloutier R, Poulin J. Incidence of venographically proved deep vein thrombosis after knee arthroscopy. Arch Intern Med 1998; 158 (01) 47-50.
• 25 Durica S, Raskob GE, Johnson C. et al. Incidence of deep-vein thrombosis after arthroscopic knee surgery. Thromb Haemost 1997; 77 (Suppl) 741a.
• 26 Kearon C, Hirsh J. Starting prophylaxis for venous thromboembolism postoperatively. Arch Intern Med 1995; 155: 366-372.
• 27 Lumpkin MM. FDA Alert. FDA public health advisory. Anesthesiology 1998; 88: 27A-28A.
• 28 Vandermeulen EP, van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994; 79: 1165-1177.
• 29 Horlocker TT, Heit JA. Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis regimens and guidelines for regional anesthetic management. Anesth Analg 1997; 85: 874-885.
• 30 Horlocker TT, Wedel DJ. Neuraxial block and low-molecular-weight heparin: balancing perioperative analgesia and thromboprophylaxis. Reg Anesth Pain Med 1998; 6 (Suppl. 02) 164-177.
• 31 Hull RD, Brant RF, Pineo GF, Stein PD, Raskob GE, Valentine KA. Preoperative vs postoperative initiation of low-molecular-weight heparin prophylaxis against venous thromboembolism in patients undergoing elective hip replacement. Arch Intern Med 1999; 159: 137-141.
• 32 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.
• 33 Haas SB, Tribus CB, Insall JN, Becker MW, Windsor RE. The significance of calf thrombi after total knee arthroplasty. J Bone Joint Surg Br 1992; 74: 799-802.
• 34 Pellegrini VD, Langhans MJ, Totterman S, Marder VJ, Francis CW. Embolic complications of calf thrombosis following total hip arthroplasty. J Arthroplasty 1993; 8: 449-457.
• 35 Lohr JM, Kerr TM, Lutter KS, Cranley RD, Spirtoff K, Cranley JJ. Lower extremity calf thrombosis: to treat or not to treat?. J Vasc Surg 1991; 14: 618-623.
• 36 Shull KC, Nicolaides AN, Fernandes E, Fernandes J, Miles C, Horner J, Needham T, Cooke ED, Eastcott FH. Significance of popliteal reflux in relation to ambulatory venous pressure and ulceration. Arch Surg 1979; 114: 1304-1306.
• 37 Christopoulos DG, Nicolaides AN, Szendro G, Irvine AT, Bull ML, Eastcott HH. Air-plethysmography and the effect of elastic compression on venous hemodynamics of the leg. J Vasc Surg 1987; 5: 148-159.
• 38 Araki CT, Back TL, Padberg FT, Thompson PN, Jamil Z, Lee BC, Duran WN, Hobson II RW. The significance of calf muscle pump function in venous ulceration. J Vasc Surg 1994; 20: 872-879.
• 39 Serafini S, Beltrametti C, Siragusa S. et al. Post-thrombotic syndrome after asymptomatic postoperative deep vein thrombosis: an inception cohort study. Thromb Haemost 1997; 77 (Suppl) 718a.
• 40 Leizorovicz A, Haugh MC, Chapuis F-R, Samama MM, Boissel JP. Low-molecular-weight heparin in prevention of perioperative thrombosis. BMJ 1992; 305: 913-920.
• 41 Nurmohamed MT, Rosendaal FR, Buller HR, Dekker E, Hommes DW, Vandenbroucke JP, Briet E. Low molecular weight heparin in the prophylaxis of venous thrombosis: a meta-analysis. Lancet 1992; 340: 152-156.
• 42 Koch A, Bouges S, Ziegler S, Dinkel H, Daures JP, Victor N. Low molecular weight heparin and unfractionated heparin in thromboprophylaxis after major surgical intervention: update of previous meta-analyses. Br J Surg 1997; 84: 750-759.
• 43 Palmer AJ, Koppenhagen K, Kirchhof B, Weber U, Bergemann R. Efficacy and safety of low molecular weight hepairn, unfractionated heparin and warfarin for thromboembolism prophylaxis in orthopaedic surgery: a meta-analysis of randomised clinical trials. Haemostasis 1997; 27: 75-84.
• 44 Hull RD, Pineo GF. Prophylaxis of deep venous thrombosis and pulmonary embolism: current recommendations. Medical Clinics of North America 1998; 82 (03) 477-493.
• 45 Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, Saibil EA, Hamilton PA. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996; 335 (10) 701-707.
• 46 Kujath P, Spannagel U, Habscheid W. Incidence and prophylaxis of deep vein thrombosis in outpatients with injury of the lower limbs. Haemostasis 1996; 23 (Suppl. 01) 20-26.
• 47 Kock H-J, Schmit-Neuerberg KP, Hanke J. et al. Thromboprophylaxis with low-molecular-weight heparin in outpatients with plaster-cast immobilization of the leg. Lancet 1995; 346: 459-461