Home > Full Text Reviews > Venous Thromboembolism Prophylaxis in...

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.

Cover of Venous Thromboembolism Prophylaxis in Orthopedic Surgery

Venous Thromboembolism Prophylaxis in Orthopedic Surgery

Comparative Effectiveness Reviews, No. 49

Principal Investigators: Diana M Sobieraj, PharmD, Craig I Coleman, PharmD, Vanita Tongbram, MBBS, MPH, Soyon Lee, PharmD, Jennifer Colby, PharmD, Wendy T Chen, PharmD, Sagar S Makanji, PharmD, Ajibade Ashaye, MD, MPH, Jeffrey Kluger, MD, FACC, and C Michael White, PharmD, FCP, FCCP.

University of Connecticut/Hartford Hospital Evidence-based Practice Center
Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Mar.
Report No.: 12-EHC020-EF
Copyright and Permissions

Structured Abstract


This is an evidence report prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center (EPC) examining the comparative efficacy and safety of prophylaxis for venous thromboembolism in major orthopedic surgery (total hip replacement [THR], total knee replacement [TKR], and hip fracture surgery [HFS]) and other nonmajor orthopedic surgeries (knee arthroscopy, injuries distal to the hip requiring surgery, and elective spine surgery).

Data Sources:

Medline, the Cochrane Central Register of Controlled Trials, and Scopus from 1980 to May 2011 with no language restrictions.

Review Methods:

Controlled trials of any size and controlled observational studies with ≥750 subjects were included in our comparative effectiveness review if they were in patients undergoing one of six a priori defined orthopedic surgeries; provided data on prespecified intermediate, final health, or harms outcomes; defined deep vein thrombosis (DVT) and pulmonary embolism (PE) according to rigorous criteria (where applicable), and included prophylactic products (pharmacologic or mechanical) available in the United States. Using predefined criteria, data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes were extracted. All of the available data were qualitatively evaluated and where possible, statistically pooled. We used random effects derived relative risks (RR) for most analyses and Peto's Odds Ratios (OR) in comparisons of rare events both with 95 percent confidence intervals (CIs). I2 was used to detect statistical heterogeneity and Egger's weighted regression statistics were used to assess for publication bias. The strength of evidence (SOE) and applicability of evidence (AOE) for each outcome was rated as insufficient (I), low (L), moderate (M), or high (H).


In major orthopedic surgery (THR, TKR, and HFS, respectively), the incidence of DVT (39 percent, 53 percent, 47 percent), PE (6 percent, 1 percent, 3 percent), major bleeding (1 percent, 3 percent, 8 percent), and minor bleeding (5 percent, 5 percent, not reported) were reported in the placebo/control groups of clinical trials. The SOE and AOE were predominantly low for THR and TKR and was insufficient HFS. In major orthopedic surgery, pharmacologic prophylaxis reduced major venous thromboembolism (VTE) (OR 0.21 [0.05 to 0.95], SOE: L, AOE: L), DVT (RR 0.56 [0.47 to 0.68], SOE: M, AOE: L), and proximal DVT (pDVT) (RR 0.53 [0.39 to 0.74], SOE: H, AOE: L), but increased minor bleeding (RR 1.67 [1.18 to 2.38], SOE: H, AOE: M). Prolonged prophylaxis for ≥28 days was superior to prophylaxis for 7 to 10 at reducing symptomatic objectively confirmed VTE (RR 0.38 [0.19 to 0.77], SOE: M, AOE: L), PE (OR 0.13 [0.04 to 0.47], SOE: H, AOE: L), DVT (RR 0.37 [0.21 to 0.64], SOE: M, AOE: M), and pDVT (RR 0.29 [0.16 to 0.52], SOE: H, AOE: M) but increased minor bleeding (OR 2.44 [1.41 to 4.20], SOE: H, AOE: M). Using both pharmacologic and mechanical prophylaxis reduced DVT (RR 0.48 [0.32 to 0.72] SOE: M, AOE: M) versus pharmacologic prophylaxis alone.

Low molecular weight heparins (LMWHs) reduced PE (OR 0.48 [0.24 to 0.95], SOE: M, AOE: L), DVT (RR 0.80 [0.65 to 0.99], SOE: M, AOE: L), pDVT (RR 0.60 [0.38 to 0.93], SOE: H, AOE: L), major bleeding (OR 0.57 [0.37 to 0.88], SOE: H, AOE: L), and heparin induced thrombocytopenia (OR 0.12 [0.03 to 0.43], SOE: M, AOE: L) versus unfractionated heparin. LMWHs reduced DVT (RR 0.66 [0.55 to 0.79], SOE: L, AOE: M) but increased major bleeding (RR 1.92 [1.27 to 2.91], SOE: H, AOE: M), minor bleeding (RR 1.23 [1.06 to 1.43], SOE: M, AOE: M), and surgical site bleeding (OR 2.63 [1.31 to 5.28], SOE: L, AOE: L) versus vitamin K antagonists. LMWHs increased DVT (RR 1.99 [1.57 to 2.51], SOE: M, AOE: L) and pDVT (OR 2.19 [1.52 to 3.16], SOE: L, AOE: L) but reduced major bleeding (OR 0.65 [0.48 to 0.89], SOE: M, AOE: L) versus factor Xa inhibitors. Antiplatelets increased DVT (1.63 [1.11 to 2.39], SOE: M, AOE: L) versus mechanical prophylaxis. Unfractionated heparin increased DVT (RR 2.31 [1.34 to 4.00], SOE: M, AOE: L) and pDVT (OR 4.74 [2.99 to 7.49], SOE: M, AOE: L) versus direct thrombin inhibitors. Intermittent compression stocking decreased DVT (RR 0.06 [0.01 to 0.41], SOE: L, AOE: L) versus graduated compression stockings.

We did not have adequate information to evaluate the role of inferior vena cava filter (IVC) filters or to evaluate the impact of prophylaxis on nonmajor orthopedic surgeries.


In major orthopedic surgery, while the risk of developing deep vein thrombosis is highest followed by pulmonary embolism and major bleeding, there are inadequate data to say whether or not deep vein thrombosis causes pulmonary embolism or is an independent predictor of pulmonary embolism. The balance of benefits to harms is favorable for providing prophylaxis to these patients and to extend the period of prophylaxis beyond the standard 7–10 days. The comparative balance of benefits to harms for LMWHs are superior to unfractionated heparin. Other interclass comparisons either could not be made due to lack of data, showed similarities between classes on outcomes, or had offsetting effects where benefits of one class on efficacy was tempered by an increased risk of bleeding. The balance of benefits to harms for combined pharmacologic plus mechanical prophylaxis versus either strategy alone could not be determined. We could not determine the impact of IVC filters on outcomes or the impact of prophylaxis on the nonmajor orthopedic surgeries evaluated.


Evidence-based Practice Center Directors: C Michael White, PharmD, FCP, FCCP; Craig I Coleman, PharmD.

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2007-10067-I. Prepared by: University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, CT

Suggested citation:

Sobieraj DM, Coleman CI, Tongbram V, Lee S, Colby J, Chen WT, Makanji SS, Ashaye A, Kluger J, White CM. Venous Thromboembolism in Orthopedic Surgery. Comparative Effectiveness Review No. 49. (Prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center under Contract No. 290-2007-10067-I.) AHRQ Publication No. 12-EHC020-EF. Rockville, MD: Agency for Healthcare Research and Quality. March 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

This report is based on research conducted by the University of Connecticut/Hartford Hospital Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10067-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.


540 Gaither Road, Rockville, MD 20850; www​.ahrq.gov


AHRQ (US Agency for Healthcare Research and Quality)

PubMed Health Blog...

read all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...