Articles |

Advances and Contemporary Issues in Prophylaxis for Deep Vein Thrombosis* FREE TO VIEW

Jack Hirsh, CM, MD, DSc, FCCP
Author and Funding Information

*From McMaster University, Hamilton, Ontario, Canada.

Correspondence to: Jack Hirsh, CM, MD, DSc, FCCP, Hamilton Civic Hospital Research Center, 711 Concession St, Hamilton, ON L8V 1C3 Canada; e-mail: jhirsh@thrombosis.hhscr.org

Chest. 2003;124(6_suppl):347S-348S. doi:10.1378/chest.124.6_suppl.347S
Text Size: A A A
Published online

The need for prophylaxis against venous thromboembolism in high-risk patients undergoing surgery is widely accepted. Although effective and safe agents are available, a number of issues remain unresolved. These contemporary issues are addressed in this supplement, which includes the proceedings of a postgraduate course on “Contemporary Issues in Prophylaxis of Deep Vein Thrombosis,” held at the American College of Chest Physicians Meeting in San Diego in November 2002.

Dr. Anderson and associates discuss temporal trends in the use of prophylaxis in total hip or knee surgery between 1996 and 2001. Based on a Hip and Knee Registry of self-reported data from 464 orthopedic surgeons, the authors report that the mean length of hospital stay has decreased and is now < 4 days and that the use of spinal or epidural anesthesia has increased and is now used in approximately 50% of patients in the registry. In 2001, approximately 90% of patients received an acceptable form of prophylaxis during their hospital stay, while approximately 50% of patients received prophylaxis for > 21 days; these findings represent a small increase from the 1996 levels.

Dr. Raskob reviews the literature on the controversial issue of the timing of the first dose of prophylaxis with low-molecular-weight heparin (LMWH) and newer anticoagulants. Data on direct comparisons of different times for administering the first dose, using the same anticoagulant regimen, are limited to one randomized trial. Therefore, many of the conclusions on optimal timing of first dose are based on subgroup analysis or indirect comparisons, which by their very nature are hypothesis forming. The totality of data suggests that here is no advantage in commencing prophylaxis preoperatively, provided that the first postoperative dose is administered approximately 6 h after surgery. Preoperative dosing within 2 h of surgery with LMWH increases the risk of bleeding, compared to postoperative prophylaxis. Initiation of the new anticoagulant fondaparinux earlier than 6 h before surgery appears to increase the risk of bleeding without an increase in efficacy. The relative efficacy and safety of commencing the first dose of prophylaxis either 6 h or 12 h postoperatively requires evaluation in randomized trials.

Dr. Kearon reviews the results of clinical studies examining the relative efficacy and safety of either stopping or continuing prophylaxis after hospital discharge in patients undergoing total hip replacement surgery. There is very good evidence, based on direct comparisons, that the frequency of asymptomatic thrombosis detected by venography is reduced by approximately two thirds if prophylaxis with LMWH is continued for approximately 4 weeks postoperatively. Dr. Kearon also concludes that the risk of continuing postoperative prophylaxis for 4 weeks with LMWH reduces the risk of symptomatic venous thromboembolism by approximately two thirds. Based on indirect comparisons, compared with LMWH, Dr. Kearon hypothesizes that the efficacy of extended prophylaxis is expected to be greater with fondaparinux, similar with warfarin, and less with aspirin, and that extended prophylaxis is expected to show less benefit after total knee than total hip replacement.

Drs. Geerts and Selby discuss the poorly studied field of prevention of venous thromboembolism in a critical care setting. In their systematic review of the literature, they note that most patients in critical care units have at least one risk factor, and that most have multiple risk factors; the risk of objectively confirmed thrombosis is substantial; and the limited data indicate that both low-dose unfractionated heparin and LMWH are effective. They note that because of the unstable nature of patients in a critical care unit, selection of the most appropriate antithrombotic agent for prophylaxis is a challenge and requires daily review, based on the changing condition of the patient.

Based on their proven efficacy and relative safety, either LMWH or warfarin is recommended for prophylaxis by the American College of Chest Physicians Consensus Conference in major orthopedic surgery. There is, however, room for improvement. Stimulated by this perceived clinical need, the relative efficacy and safety of a new anticoagulant, fondaparinux, has been compared with the LMWH, enoxaparin, in a number of randomized trials in total hip, total knee, and fractured hip surgery. Dr. Bauer reviews the pharmacology of fondaparinux, and Dr. Turpie describes the clinical development program in orthopedic surgery. Fondaparinux, a synthetic pentasaccharide with high affinity for its specific target, antithrombin, catalyzes the inhibition of factor Xa. Fondaparinux has excellent bioavailability, does not bind to plasma proteins or platelets, and has a half-life of 17 h, allowing once-daily dosing by subcutaneous injection. It does not crossreact with heparin-induced thrombocytopenia antibodies, and is cleared through a renal mechanism. Fondaparinux has a favorable efficacy-to-safety profile in experimental animal models.

The relative efficacy and safety of fondaparinux and enoxaparin have been compared in four randomized, double-blind trials. In a pooled analysis of the individual studies, fondaparinux started postoperatively reduced the incidence of venous thrombosis detected by venography at approximately 11 days by approximately 55%, and showed a favorable efficacy-to-safety ratio. In a fifth trial, the effectiveness of extended-use (4 weeks) fondaparinux was compared with 1 week in patients with hip fracture. Extended-use fondaparinux produced a marked reduction (approximately 90%) in asymptomatic (venograpahically detected) and symptomatic thrombosis. Fondaparinux is now approved for major orthopedic surgery. Finally, Dr. Davidson and colleagues discuss the principles of the economics of venous thromboembolism prophylaxis, an important topic in the current climate of cost containment.

Abbreviation: LMWH = low-molecular-weight heparin

Dr. Hirsh is a member of the Sanofi-Synthelabo International Advisory Board.

Dr. Hirsh has received an honorarium from the American College of Chest Physicians for the preparation of this article.




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543