DVT Prophylaxis in Hip & Knee Replacement Surgery: Controversies in 2008

James P. Waddell, M.D., FRCSC
Professor, Division of Orthopaedic Surgery University of Toronto
Toronto, ON

Routine thromboprophylaxis following elective hip and knee replacement surgery remains a controversial topic. No one disputes that patients undergoing these surgical procedures are at risk for deep vein thrombosis1. The combination of stasis, endothelial wall injury and hypercoagulability are almost routine following this type of hip and knee surgery. It is because of the prevalence of deep vein thrombosis in these patients that they are frequently selected for study in large clinical trials examining the efficacy of various antithrombotic agents.

Much of the discord surrounding routine thromboprophylaxis for hip and knee replacement surgery relates to the clinical trials studying these patients. They report a high incidence of venographically demonstrated thrombi in patients days or weeks following the surgical procedure in question. Only a tiny fraction of these patients with venographically proven thrombi are in fact symptomatic and an even smaller number of patients in these large studies ever develop symptomatic pulmonary embolism proven by diagnostic imaging2,3,4.

The flip side of this debate relates to surgical bleeding. Every study which looks at the role of chemical thromboprophylaxis documents surgical bleeding as a recognized complication of the use of chemical thromboprophylaxis. Surgical bleeding postoperatively can have a significant deleterious effect on the outcome for the patient. The bleeding may be of such severity that the patient has to be returned to the operating room for evacuation of a haematoma or, in lesser instances, may be of such magnitude that the rehabilitation of the patient is interrupted, particularly in knee replacement surgery. Knees distended by a contained haematoma are painful and the bulk of the haematoma may interfere with mobilization of the joint and result in a decreased ultimate range of motion or failure to correct a flexion contracture. The wound drainage in knee arthroplasty, frequently associated with postoperative surgical bleeding, has also recently been linked to an increased rate of prosthetic infection11.

While a number of studies document a significant rate of surgical bleeding following chemical thromboprophylaxis, other studies have documented no significant increase in surgical bleeding among different chemical agents5,6. Mechanical devices such as intermittent pneumatic compression devices have been shown to have a beneficial effect in decreasing the incidence of venographically proven deep vein thrombosis in clinical trials. These devices alone have a lower efficacy compared to their use in conjunction with chemical prophylaxis7,8.

The American College of Chest Physicians has, over a number of years, published guidelines for thromboprophylaxis following elective hip and knee replacement surgery. These guidelines are based on published evidence regarding the efficacy of a variety of mechanical and chemical regimens. They discount the efficacy of aspirin alone as an antithrombotic agent and promote (based on levels of evidence) the use of low-molecular-weight heparin, synthetic pentasaccharides and warfarin as the chemical agents of choice. They also suggest that mechanical prophylaxis alone is inadequate protection for patients. These guidelines recommend a prolonged period of anticoagulation for patients undergoing hip arthroplasty (and patients undergoing surgical repair of proximal femoral fractures) and a somewhat shorter period of time for patients undergoing elective knee replacement surgery.

The American Academy of Orthopaedic Surgeons has published clinical guidelines on the prevention of pulmonary embolism in patients undergoing total knee or hip arthroplasty. These guidelines differ significantly from those issued by the American College of Chest Physicians in that they recommend aspirin as a chemoprophylactic agent of equal value to the other chemical agents; furthermore they recommend chemoprophylaxis for a shorter period of time for both hip and knee replacement patients than is recommended in the Chest guidelines.

The American Academy guidelines do recognize that postoperative thromboprophylaxis is appropriate for patients undergoing elective hip and knee replacement surgery. The lesson we should take, despite the seeming disparity between the chest physicians and the orthopaedic surgeons, is not to focus on differences between recommended regimes or duration but rather on the now, almost universally accepted, need for some type of effective programme for our patients.

I personally do not favour aspirin as a thromboprophylactic agent; it does have proven value in the mitigation of risk for arterial thrombosis but because of its mechanism of action, is much less effective in the prevention of venous thrombosis. Its attributes are ease of administration, low risk of post-surgical bleeding and the lack of need for postoperative monitoring. The low-molecular-weight heparin and synthetic pentasaccharides, on the other hand, require subcutaneous injection and have a potentially higher rate of postoperative bleeding as well as a significantly greater cost than aspirin. Warfarin is cheap and easy to administer but requires ongoing close monitoring if it is to be both effective and safe.

The recent commercial introduction of oral Factor Xa inhibitors may address many of the concerns that have led to the conflicting recommendations regarding postoperative anticoagulation. Oral administration allows for simple extended thromboprophylaxis following hospital discharge and lack of need for monitoring greatly increases the efficacy and convenience for extended post-hospital discharge thromboprophylaxis. The rate of postoperative bleeding appears to be low and efficacy in the prevention of deep vein thrombosis in published clinical trials is at least equivalent to that of the low-molecular-weight heparins.

One thing is certain: the introduction of the Factor Xa inhibitors is going to result in a revision of both the American College of Chest Physicians and the American Academy of Orthopaedic Surgeons guidelines for thromboprophylaxis following hip and knee replacement surgery.

References

  1. Geerts, et al. Chest 2008:133, 381S-453S.
  2. Eriksson B.I., Bergqvist D., Kalebo P., Dahl O.E., Lindbratt S., Bylock A., et al: Cimelagatran and melagatran compared with dalteparin for prevention of venue thromboembolism after total hip or knee replacement: the METHRO II randomized trial. Lancet 2002 Nov 9; 360(9344):1441-1447.
  3. Eriksson B.I., Borris L., Dahl O.E., Haas S., Huisman M.V., Kakkar A.K., et al: Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement. Journal of Thrombosis & Haemostasis 2006 Jan;4(1):121-128.
  4. Lassen M.R., Bauer K.A., Eriksson B.I., Turpie A.G.: European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venue thromboembolism in elective hip replacement surgery; a randomized double-blind comparison. Lancet 2002 May 18;359(9319):1715-1720.
  5. Colwell C.W., Jr., Berkowitz S.D., Davidson B.L., Lotke P.A., Ginsberg J.S., Lieberman J.R., et al: Comparison of ximelagatran, an oral direct thrombin inhibitor, with enoxaparin for the prevention of venous thromboembolism following total hip replacement. A randomized, double-blind study. Journal of Thrombosis & Haemostasis 2003 Oct;1(10):2119-2130.
  6. Eriksson B.I., Dahl O.E., Buller H.R., Hettiarachchi R., Rosencher N., Bravo M.L., et al: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromoboembolic events following total hip or knee replacement: the BISTRO II randomized trial. Journal of Thrombosis and Haemostasis 2005 Jan;3(1):103-111.
  7. Silbersack Y., Taute B.M., Hein W., Podhaisky H.: Prevention of deep-vein thrombosis after total hip and knee replacement. Low molecular-weight heparin in combination with intermittent pneumatic compression. Journal of Bone & Joint Surgery - British Volume 2004 Aug;86(6):809-812.
  8. Warwick D., Harrison J., Glew D., Mitchelmore A., Peters T.J., Donovan J.: Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement. A prospective, randomized trial 550. Journal of Bone & Joint Surgery, American Volume 1998 Aug;80(8):1158-1166.
  9. Eriksson B.I., Borris L.C., Friedman R.J., Haas S., Huisman M.V., Kakkar A.K., Bandel T.J., Beckmann H., Muehlhofer E., Misselwitz F., Geerts W: Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Hip Arthroplasty. The New England Journal of Medicine 2008 Jun;358(26):2765-2775.
  10.  Kakkar A.K., Brenner B., Dahl O.E., Eriksson B.I., Mouret P., Muntz J. Soglian A.G., Pap A.F., Misselwitz F., Haas S.: Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomized controlled trial. Lancet 2008 June. DOI:10.1016/S0140-6736(08)60880-6
  11. Galat D.D., McGovern S.C., Hanssen A.D., Larson D.R., Harrington J.R., Clarke H.D.: Early return to surgery for evacuation of a postoperative hematoma after primary total knee arthroplasty. Journal of Bone & Joint Surgery - American Volume 2008;90:2331-2336.

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