Venous Thromboembolism Prophylaxis in Orthopedic Surgery [Entered Retrospectively]

Project Summary Title and Description

Title
Venous Thromboembolism Prophylaxis in Orthopedic Surgery [Entered Retrospectively]
Description
Objectives: 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); Results: 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; Conclusions: 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.
Attribution
N/A
Authors of Report
N/A
Methodology description
A systematic literature search of Medline, the Cochrane Central Register of Controlled Trials, and Scopus from 1980 to September 2010 was conducted with no language restrictions. The year 1980 was used as a restriction to reflect contemporary practice. Two separate literature searches were conducted. The first search was used to identify studies that evaluated pharmacologic, mechanical, or inferior vena cava filter methods of thromboprophylaxis in patients undergoing major orthopedic surgery, describe the association between patient, surgical, or postsurgical characteristics and VTE or bleeding, or describe the association between intermediate and final health outcomes to answer KQs 1 through 9. The second search was used to identify studies which evaluate pharmacologic or mechanical methods of thromboprophylaxis in patients undergoing knee arthroscopy, surgical repair of a lower extremity injury distal to the hip, or elective spine surgery to answer KQs 10 and 11. Backward citation tracking was also conducted. A grey literature search of regulatory documents, abstracts, and ongoing clinical trials was conducted by the Scientific Resource Center and reviewed by two independent investigators for inclusion into our literature base by applying the same a priori defined inclusion criteria defined below. The literature searches were updated in May 2011. Two independent investigators assessed studies for inclusion in a parallel manner based on a priori defined criteria. In evaluating all KQs, randomized controlled trials (RCTs) of any size or controlled observational studies (case controlled or cohort studies) enrolling at least 750 patients were included if they explicitly reported the use of imaging studies to confirm VTE events (Doppler ultrasound or venography for DVT and spiral computed tomography [CT] angiography or ventilation/perfusion [V/Q] scan with either Prospective Investigation of Pulmonary Embolism Diagnosis [PIOPED] criteria or high clinical suspicion based on symptoms for PE). Observational studies that enrolled fewer than 750 subjects were excluded because numerous RCTs in this literature base enroll over 500 participants, with the most contemporary trials enrolling over 1,000 participants. Therefore observational studies would need to be of larger size to provide additional valuable information on outcomes of interest and applicability. Additional inclusion criteria were used specific to each KQ and are stated below.
PROSPERO
N/A
DOI
10.7301/Z0H12ZXH
Notes
*** The systematic review data of this published project was retrospectively imported into SRDR by the Brown EPC on behalf of the Connecticut/Hartford Hospital Evidence-based Practice Center and the Agency for Healthcare Research and Quality (AHRQ). For access to the full report available on the AHRQ website, follow this link: http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=999 *** This systematic review of the literature will address the following key questions: KQ 1: In patients undergoing major orthopedic surgery (total hip or knee replacement or hip fracture surgery) what is the baseline postoperative risk of VTE and bleeding outcomes in contemporary practice? KQ 2: In patients undergoing major orthopedic surgery (total hip or knee replacement or hip fracture surgery) what patient, surgical, or postsurgical characteristics predict or differentiate patient risk of VTE and bleeding outcomes in contemporary practice? KQ 3: In patients undergoing major orthopedic surgery (total hip or knee replacement or hip fracture surgery), in the absence of final health outcomes, can the risk for such outcomes reliably be estimated by measuring intermediate outcomes, such as DVT (asymptomatic or symptomatic, proximal or distal) as detected by venography or ultrasound? KQ 4: In patients undergoing major orthopedic surgery (total hip or knee replacement, hip fracture surgery), what is the relative impact of thromboprophylaxis compared with no thromboprophylaxis on symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, post thrombotic syndrome (PTS), mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion,heparin-induced thrombocytopenia (HIT), discomfort, readmission, and reoperation? Thromboprophylaxis includes any pharmacologic agent within the defined classes (oral antiplatelet agents, injectable low molecular weight heparins [LMWHs], injectable unfractionated heparin [UFH], injectable or oral factor Xa inhibitors, injectable or oral direct thrombin inhibitors [DTIs], oral vitamin K antagonists [VKAs]) or any external mechanical intervention within the defined classes (graduated compression, intermittent pneumatic compression, or venous foot pump). KQ 5: In patients undergoing major orthopedic surgery (total hip or knee replacement, hip fracture surgery), what is the comparative efficacy between classes of agents on outcomes: symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, PTS, mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion, HIT, discomfort, readmission, and reoperation? Classes include oral antiplatelet agents, injectable LMWHs, injectable UFH, injectable or oral factor Xa inhibitors, injectable or oral DTIs, oral VKAs, and mechanical interventions. KQ 6: In patients undergoing major orthopedic surgery (total hip or knee replacement or hip fracture surgery), what is the comparative efficacy of individual agents within classes (LMWH and mechanical devices) on symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, PTS, mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion, HIT, discomfort, readmission, and reoperation? KQ 7: In patients undergoing major orthopedic surgery (total hip or knee replacement, hip fracture surgery), what are the effect estimates of combined pharmacologic and mechanical modalities versus single modality on symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, PTS, mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion, HIT, discomfort, readmission, and reoperation? KQ 8: In patients undergoing major orthopedic surgery (total hip or knee replacement, hip fracture surgery), regardless of thromboprophylaxis method, what are the effects of prolonging thromboprophylaxis for 28 days or longer compared with thromboprophylaxis for 7 to 10 days on symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, PTS, mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion, HIT, discomfort, readmission, and reoperation? KQ 9: In patients undergoing major orthopedic surgery (total hip or knee replacement, hip fracture surgery) who have known contraindications to antithrombotic agents, what is the relative impact of prophylactic inferior vena cava (IVC) filter placement compared with any external mechanical intervention on symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, PTS, mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion, HIT, discomfort, readmission, reoperation, and IVC filter placement associated insertion site thrombosis? KQ 10: In patients requiring knee arthroscopy, surgical repair of a lower extremity injury distal to the hip, or elective spine surgery, what is the relative impact of thromboprophylaxis (any agent, any mechanical intervention) compared with no thromboprophylaxis intervention on symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, PTS, mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion, HIT, discomfort, readmission, and reoperation? KQ 11: In patients requiring knee arthroscopy, surgical repair of a lower extremity injury distal to the hip, or elective spine surgery, what is the relative impact of injectable antithrombotic agents (LMWH vs. UFH vs. factor Xa inhibitors vs. DTIs) compared with mechanical interventions on symptomatic objectively confirmed VTE, major VTE, PE, fatal PE, nonfatal PE, PTS, mortality, mortality due to bleeding, DVT (asymptomatic or symptomatic, proximal or distal DVT), asymptomatic DVT, symptomatic DVT, proximal DVT, distal DVT, major bleeding, major bleeding leading to reoperation, minor bleeding, surgical site bleeding, bleeding leading to infection, bleeding leading to transfusion, HIT, discomfort, readmission, and reoperation? | Abbreviations for Table 5: AR = absolute risk; CI = confidence interval; DVT = deep vein thrombosis; HFS = hip fracture surgery; NR = not reported; dDVT = distal deep vein thrombosis; N = number; pDVT = proximal DVT; PE = pulmonary embolism; sDVT = symptomatic DVT; THA = total hip arthroplasty; TKA = total knee arthroplasty; WMR = weighted mean risk | Abbreviations for Table 6: aDVT = asymptomatic deep vein thrombosis; aPE = asymptomatic pulmonary embolism; ARR = absolute risk reduction; ASA = aspirin; d = days; dDVT = distal deep vein thrombosis; DVT = deep vein thrombosis; GA = general anesthesia; HFS = hip fracture surgery; IPC = intermittent pneumatic compression; IU = international units; LMWH = low molecular weight heparin; m = months; mg = milligram; NR = not reported; OR = odds ratio; PE = pulmonary embolism; pDVT = proximal deep vein thrombosis; po = by mouth; PT = prothrombin time; QD = daily; RA = regional anesthesia; sDVT = symptomatic deep vein thrombosis; sPE = symptomatic pulmonary embolism; SQ = subcutaneous; | sVTE = symptomatic venous thromboembolism; THA = total hip arthroplasty; THR = total hip replacement; TKA = total knee arthroplasty; TKR = total knee replacement; UFH = unfractionated heparin; VFP = venous foot pump; VKA = vitamin K antagonist; VTE = venous thromboembolism; WMI = weighted mean incidence; Xa = factor 10a | Abbreviations for Tables 7-9: DVT = deep vein thrombosis; PE = pulmonary embolism | |Abbreviations for Appendix D - Table 3: ALT=Alanine aminotransferase; APTT= activated partial thromboplastin time; ARF=acute renal failure; AST=aspartate aminotransferase; BID= twice daily; BMI=body mass index ; CHF=congestive heart failure; CI=contraindication; CNS=central nervous system; Cr=creatinine; CRF=chronic renal failure; CT=computed tomography scan; CUS=continuous ultrasonography; CVA= cerebraovascular accident; CVI= chronic venous insufficiency; d=day(s); dL=deciliter; DUS= Doppler ultrasound; DVT=deep vein thrombosis; EC=enteric coated; GA=general anesthesia; GCS=graduated compression stocking; GI=gastrointestinal; h=hour(s); HFS=hip fracture surgery; HIT=heparin-induced thrombocytopenia; HTN=hypertension; hx=history; INR=international normalized ratio; IPC=intermittent pneumatic compression; IU=international units; IV=intravenous; IVC=inferior vena cava; kg=kilograms; L=liter; LMWH=low molecular weight heparin; m=months; MC=multicenter; MI=myocardial infarction; min=minute(s); mg=milligrams; mmHg=millimeters of mercury; mL=mililiters; MRI=magnetic resonance imaging; NR=not reported; NSAID=nonsteroidal anti-inflammatory drug; NYHA=New York heart association PE=pulmonary embolism; PO=by mouth; PT=prothrombin time; PTS=post thrombotic syndrome; PVD=peripheral vascular disease; QD=daily; SCr= serum creatinine; SQ=subcutaneously; TCP=thrombocytopenia; THA=total hip arthroplasty; TKA=total knee arthroplasty; THR=total hip replacement; TKR=total knee replacement; TT=thromboplastin time; UFH=unfractionated heparin; UK=United Kingdom; ULN=upper limit of normal; US=ultrasound; USA=United States of American; VFP=venous foot pump; VTE=venous thromboembolism; VQ=ventilation perfusion; w=week(s); y=year(s) | Abbreviations for Appendix D - Table 4: d=day(s); DVT=deep vein thrombosis; GI=gastrointestinal; mins=minutes; PE=pulmonary embolism; QD=once daily; SC=subcutaneously; w=week(s); y=year(s) | Abbrevaitiosn for Appendix D - Table 5: ACS=acute coronary syndrome; AF=atrial fibrillation; ASA=aspirin; CECT=continuous enhanced circulation therapy; d=day(s); DVT=deep vein thrombosis; GI:=gastrointestinal; ICD-9=International Classification of Disease, Ninth Revision; ICD-9-CM=International Classification of Disease, Ninth Revision, Clinical Modification; Inc=incorporated; IPC-intermittent pneumatic compression; kg=kilograms; LMWH=low molecular weight heparin; LOS=length of stay; MC=multicenter; mg=milligrams; NOS=not otherwise specified; NR=not reported; PE=pulmonary embolism; PO=by mouth; QD=daily; SQ=subcutaneous; THR=total hip replacement; TKA=total knee arthroplasty; TKR=total knee replacement; UFH=unfractionated heparin; U=units; US=United States; VTE=venous thromboembolism; w=weeks; y=years | Abbreviations for Appendix E - Table 6: ASA=aspirin; BID=twice daily; CA=cancer; CVD=cardiovascular disease; DM=diabetes mellitus; d=day; GCS=graduated compression stocking; HFS=hip fracture surgery; g=gram; hx=history; IPC=intermittent pneumatic compression; kg=kilograms; mg=milligram; N=total number of patients; QD=daily; SD=standard deviation; sx=surgery; THR=total hip replacement; TKR=total knee replacement; UFH=unfractionated heparin; VFP=venous foot pump; VTE=venous thromboembolism; Wt=weight | Abbreviations for Appendix E - Table 7: A=anterior; AL=anteriolateral; AM=anteriomedial; ASA=aspirin; BID=twice daily; d=days; DL=direct lateral; GA=general anesthesia; GCS=graduated compression stockings; HFS=hip fracture surgery; IPC=intermittent pneumatic compression device; L=lateral; LOS=length of stay; min=minutes; mg=milligram; ML=midline longitudinal; N=number enrolled; P=posterior; PL=posteriolateral; QD=daily; RA=regional anesthesia; SD=standard deviation; THA=total hip arthroplasty; THR=total hip replacement; TKA= total knee arthroplasty; TKR=total knee replacement; TT=transtrochanteric; UFH=unfractionated heparin; VFP=venous foot pump | Abbreviations for Appendix E - Table 8: CA=cancer; CVD=cardiovascular disease; DM=diabetes mellitus; Hx=history; kg=kilograms; N=number of participants; SD=standard deviation; Wt = weight | Abbreviations for Appendix E - Table 9: d= days; GA= general anesthesia; LOS= length of stay; N= total number of patients; RA= regional anesthesia; SD= standard deviation | Abbreviations for Appendix E - Table 10: BMI=body mass index; CA=cancer; CVD=cardiovascular disease; DM=diabetes mellitus; hx=history; IPC=intermittent pneumatic compression; kg=kilograms; LMWH=low molecular weight heparin; PE=pulmonary embolism; SD=standard deviation; sVTE=symptomatic venous thromboembolism; THR=total hip replacement; TKR=total knee replacement; UFH=unfractionated heparin; VTE=venous thromboembolism; Wt=weight | Abbreviations for Appendix E - Table 11: d=day(s); GA=general anesthesia; IPC=intermittent pneumatic compression; LMWH=low molecular weight heparin; LOS=length of stay; min=minute; MP=medial parapatellar; N=total population; P=posterior; PE=pulmonary embolism; RA=regional anesthesia; SD=standard deviation; sVTE=symptomatic venous thromboembolism; THR=total hip replacement; TKR=total knee replacement; UFH=unfractionated heparin | Abbreviations for Appendix F - Table 18: BID=twice daily; cm=centimeters; d=day; dL=deciliter; DVT=deep vein thrombosis; g=gram; GCS=graduated compression stockings; GI=gastrointestinal; h=hours; Hb=hemoglobin; HFS=hip fracture surgery; IPC=intermittent pneumatic compression; mg=milligram; min=minutes; mL=mililiter; N=number of participants; n=number of participants with the event; NG=nasogastric; PRBC=packed red blood cells; QD= once daily; RBC=red blood cell; THA=total hip arthroplasty; THR=total hip replacement; TKA=total knee arthroplasty; TKR=total knee replacement; U=units; UFH=unfractionated heparin; VFP= venous foot pump | Abbreviations for Appendix F - Table 19: N=number of participants; n=number of participants with the event | Abbreviations for Appendix F - Table 20: ICD-9=International Classification of Disease, Ninth Revision; IPC=intermittent pneumatic compression; THR=total hip replacement; TKR=total knee replacement; UFH=unfractionated heparin | Abbreviations for Appendix F - Table 21: BID=twice daily; d=day; g=gram; GCS= graduated compression stockings; h=hours; HFS=hip fracture surgery; HIT=heparin-induced thrombocytopenia; IPC=intermittent pneumatic compression device; mg=milligram; n/N= total number of events/total population; QD=daily; THA=total hip arthroplasty; THR=total hip replacement; TKA=total knee arthroplasty; TKR=total knee replacement; U=units; UFH=unfractionated heparin; VFP=venous foot pump | Abbreviations for Appendix F - Tabel 22: HIT= heparin induced thrombocytopenia; N=number of participants; n=number of participants with the event | Abbreviationas for Appendix F - Table 23: HIT=heparin-induced thrombocytopenia; IPC=intermittent pneumatic compression; THR=total hip replacement; TKR=total knee replacement; UFH=unfractionated heparin |
Funding Source
The Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. Key Question 1 - Randomized controlled trials in major orthopedic surgery
2. Key Question 2 - Randomized controlled trials in nonmajor orthopedic surgery
3. Key Question 3 - Observational studies evaluating venous thromboembolism prophylaxis in major orthopedic surgery
4. Key Question 5 - Major and minor bleeding events from randomized controlled trials evaluating patients who had major and nonmajor orthopedic surgery and observational studies evalutaing venous thromboembolism prophylaxis in major orthopedic surgery
5. Key Question 6 - Adverse events from randomized controlled trials evaluating patients who had major and nonmajor orthopedic surgery and observational studies evaluating venous thromboembolism prophylaxis in major orthopedic surgery
6. Key Question 7 - Summary of previous meta-analyses evaluating the pooled incidence of outcomes of interest in patients who had major orthopedic surgery
7. Key Question 8 - Summary of previous meta-analyses relevant to key questions 2 through 8 of the report
8. Key Question 4 - Overall baseline risk of venous thromboembolism and bleeding outcomes in patients undergoing major orthopedic surgery limited to hip replacement, knee replacement, and hip fracture surgeries

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Is routine chemical thromboprophylaxis after total hip replacement really necessary in a Japanese population?
Dabigatran etexilate prevents venous thromboembolism after total knee arthroplasty in Japanese patients with a safety profile comparable to placebo.2010
Thromboembolic prophylaxis for total knee arthroplasty in Asian patients: a randomised controlled trial.
Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery.
Portable compression device and low-molecular-weight heparin compared with low-molecular-weight heparin for thromboprophylaxis after total joint arthroplasty
Prevention of postoperative venous thromboembolism in Japanese patients undergoing total hip or knee arthroplasty: two randomized, double-blind, placebo-controlled studies with three dosage regimens of enoxaparin [Total hip arthroplasty]
Prevention of postoperative venous thromboembolism in Japanese patients undergoing total hip or knee arthroplasty: two randomized, double-blind, placebo-controlled studies with three dosage regimens of enoxaparin [Total knee arthroplasty]
The effect of tourniquet release timing on perioperative blood loss in simultaneous bilateral cemented total knee arthroplasty: a prospective randomized study.2008
Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial.2007
Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial [Part B: RE-NOVATE]
The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement.
Evaluation of wound healing after total knee arthroplasty in a randomized prospective trial comparing fondaparinux with enoxaparin.
Enoxaparin and heparin comparison of deep vein thrombosis prophylaxis in total hip replacement patients.
Effect on deep venous thrombosis with flexion during total knee arthroplasty.2006
A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial.
Epidural analgesia improves early rehabilitation after total knee replacement.2005
Two mechanical devices for prophylaxis of thromboembolism after total knee arthroplasty. A prospective, randomised study.
Prevention of deep-vein thrombosis after total hip and knee replacement. Low-molecular-weight heparin in combination with intermittent pneumatic compression.
Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study.
Incidence and natural history of deep-vein thrombosis after total hip arthroplasty. A prospective and randomised clinical study.2003
Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison.
Prophylaxis against fat and bone-marrow embolism during total hip arthroplasty reduces the incidence of postoperative deep-vein thrombosis: a controlled, randomized clinical trial.2002
Prolonged thromboprophylaxis with oral anticoagulants after total hip arthroplasty: a prospective controlled randomized study.
Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial.2002
A randomised comparison of a foot pump and low-molecular-weight heparin in the prevention of deep-vein thrombosis after total knee replacement.
Intraoperative Doppler ultrasound of the femoral vein for maintaining venous patency in hip joint prosthesis implantation.2001
Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery.
Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group.
Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery.
Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin.
Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators.
Deep vein thrombosis prophylaxis in hip fractures: a comparison of the arteriovenous impulse system and aspirin.
Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge.
The use of fibrin tissue adhesive to reduce blood loss and the need for blood transfusion after total knee arthroplasty. A prospective, randomized, multicenter study.1999
Prevention of deep vein thrombosis after hip replacement--comparison between two low-molecular heparins, tinzaparin and enoxaparin.
Thromboprophylaxis in hip fracture surgery: a pilot study comparing danaparoid, enoxaparin and dalteparin. The TIFDED Study Group.-- Not Found --
The tourniquet in total knee arthroplasty. A prospective, randomised study.1999
Prophylaxis for deep vein thrombosis with aspirin or low molecular weight dextran in Korean patients undergoing total hip replacement. A randomized controlled trial.
Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study.
Low-molecular-weight heparin and partial thromboplastin time-adjusted unfractionated heparin in thromboprophylaxis after total knee and total hip arthroplasty.
Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery.1998
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.
Postoperative activation of the haemostatic system--influence of prolonged thromboprophylaxis in patients undergoing total hip arthroplasty.-- Not Found --
Prolonged thromboprophylaxis following hip replacement surgery--results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin)
Prevention of thromboembolism with use of recombinant hirudin. Results of a double-blind, multicenter trial comparing the efficacy of desirudin (Revasc) with that of unfractionated heparin in patients having a total hip replacement [Part A]
Prevention of thromboembolism with use of recombinant hirudin. Results of a double-blind, multicenter trial comparing the efficacy of desirudin (Revasc) with that of unfractionated heparin in patients having a total hip replacement [Part B]
Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin.
The post-discharge prophylactic management of the orthopedic patient with low-molecular-weight heparin: enoxaparin.
The post-hospital discharge venous thrombosis risk of the orthopedic patient.
Low molecular weight heparin associated with spinal anaesthesia and gradual compression stockings in total hip replacement surgery. Arar Study Group.
Prevention of deep-vein thrombosis after total hip replacement: direct thrombin inhibition with recombinant hirudin, CGP 39393.1996
Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement. A randomised controlled trial.
The frequency of venous thrombosis in cemented and non-cemented hip arthroplasty.1996
Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin.
Aspirin and warfarin for thromboembolic disease after total joint arthroplasty.
Randomized, comparative, open study to assess the efficacy and safety of enoxaparin compared with unfractionated heparin in the prophylaxis of venous thromboembolism in patients undergoing total hip arthroplasty1996
Prophylaxis of deep venous thrombosis after total hip arthroplasty by using intermittent compression of the plantar venous plexus.1996
A comparison of intermittent calf compression and enoxaparin for thromboprophylaxis in total hip replacement. A pilot study.
Prophylaxis against deep venous thrombosis after total knee arthroplasty. Pneumatic plantar compression and aspirin compared with aspirin alone.
Randomized trial of epidural versus general anesthesia: outcomes after primary total knee replacement.1996
Effects of tourniquet during total knee arthroplasty. A prospective randomised study.1995
Low molecular weight heparin (enoxaparin) compared with unfractionated heparin in prophylaxis of deep venous thrombosis and pulmonary embolism in patients undergoing hip replacement.
Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep venous thrombosis after elective knee arthroplasty. Enoxaparin Clinical Trial Group.
Perioperative low-molecular-weight heparin. Is it effective and safe.
Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety. Enoxaparin Clinical Trial Group.
Prophylaxis for the prevention of venous thromboembolism after total knee arthroplasty. A comparison between unfractionated and low-molecular-weight heparin.
The prevalence of deep venous thrombosis after total hip arthroplasty with hypotensive epidural anesthesia.
Prevention of deep-vein thrombosis following total hip replacement surgery with enoxaparin versus unfractionated heparin: a pharmacoeconomic evaluation.
Prophylaxis against deep-vein thrombosis in total hip replacement. Comparison of heparin and foot impulse pump.
A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation.
A venous foot pump reduces thrombosis after total hip replacement.
Comparison of warfarin and external pneumatic compression in prevention of venous thrombosis after total hip replacement.
The thromboprophylactic effect of a low-molecular-weight heparin (Fragmin) in hip fracture surgery. A placebo-controlled study.
Thrombo-embolic prophylaxis in total knee replacement. Evaluation of the A-V Impulse System.
Prospective randomized trial of sequential compression devices vs low-dose warfarin for deep venous thrombosis prophylaxis in total hip arthroplasty.
Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. Comparison of low-molecular-weight heparin and unfractionated heparin.
Antithrombotic efficacy of continuous extradural analgesia after knee replacement.1991
Prevention of thromboembolism in 190 hip arthroplasties. Comparison of LMW heparin and placebo.
Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin.
Prevention of thromboembolic disease following total knee arthroplasty. Epidural versus general anesthesia.1991
Prevention of deep vein thrombosis after total hip replacement. The effect of low-molecular-weight heparin with spinal and general anaesthesia.
Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery. A placebo controlled study.
Intermittent pneumatic compression to prevent proximal deep venous thrombosis during and after total hip replacement. A prospective, randomized study of compression alone, compression and aspirin, and compression and low-dose warfarin.
Pneumatic sequential-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty.
Levels of thrombin--antithrombin-III complex and factor VIII activity in relation to post-operative deep vein thrombosis and influence of prophylaxis with a low-molecular-weight heparin.1990
Randomized trial of a low-molecular-weight heparin (Kabi 2165) versus adjusted-dose subcutaneous standard heparin in the prophylaxis of deep-vein thrombosis after elective hip surgery.
A prospective double-blind trial of a low molecular weight heparin once daily compared with conventional low-dose heparin three times daily to prevent pulmonary embolism and venous thrombosis in patients with hip fracture.
A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip.
Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement.
Comparison of the efficacy and tolerance of Kabi 2165 and standard heparin in the prevention of deep venous thrombosis in total hip prosthesis.
Low-dose warfarin versus external pneumatic compression for prophylaxis against venous thromboembolism following total hip replacement.
Prophylaxis of thromboembolic disease and platelet-related changes following total hip replacement: a comparative study of aspirin and heparin-dihydroergotamine.
A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery.
Effects of anaesthetic technique on deep vein thrombosis. A comparison of subarachnoid and general anaesthesia.1985
Deep vein thrombosis following hip surgery. Relation to activated factor X inhibitor activity: effect of heparin and dextran.
Comparative influences of epidural and general anaesthesia on deep venous thrombosis and pulmonary embolism after total hip replacement.1981
Prevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression.
Portable compression device and low-molecular-weight heparin compared with low-molecular-weight heparin for thromboprophylaxis after total joint arthroplasty [Total hip arthroplasty]
Portable compression device and low-molecular-weight heparin compared with low-molecular-weight heparin for thromboprophylaxis after total joint arthroplasty [Total knee arthroplasty]
Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group [Total hip replacement]
Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group [Total knee replacement]2001
Pneumatic sequential-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty [Unilateral]
Pneumatic sequential-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty [Bilateral]
Prolonged thromboprophylaxis with dalteparin after surgical treatment of achilles tendon rupture: a randomized, placebo-controlled study.2007
Prevention of deep-vein thrombosis in ambulatory arthroscopic knee surgery: A randomized trial of prophylaxis with low--molecular weight heparin.2002
Does aspirin have a role in venous thromboembolism prophylaxis in total knee arthroplasty patients?
Comparing the quality of care across Belgian hospitals from medical basic datasets: the case of thromboembolism prophylaxis after major orthopaedic surgery.2010
The incidence of fatal pulmonary embolism after primary hip and knee replacement in a consecutive series of 4253 patients.2009
Venous thromboembolic disease reduction with a portable pneumatic compression device.2009
Metabolic syndrome and the incidence of symptomatic deep vein thrombosis following total knee arthroplasty.2009
Symptomatic venous thromboembolism following a hip fracture.2009
Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk assessment.2007
Venous thromboembolism after orthopedic surgery: implications of the choice for prophylaxis.2007
Epidemiology of venous thromboembolism in Asian patients undergoing major orthopedic surgery without thromboprophylaxis. The SMART study.
Does anticoagulation do more harm than good?: A comparison of patients treated without prophylaxis and patients treated with low-dose warfarin after total knee arthroplasty.2003
Effect of mechanical compression on the prevalence of proximal deep venous thrombosis as assessed by magnetic resonance venography.
The efficacy of prophylaxis with low-dose warfarin for prevention of pulmonary embolism following total hip arthroplasty.1997
The significance of calf thrombi after total knee arthroplasty.1992
Pulmonary embolism in total hip and knee arthroplasty. Risk factors in patients on warfarin prophylaxis and analysis of the prothrombin time as an indicator of warfarin's prophylactic effect.1992
The incidence of fatal pulmonary embolism after primary hip and knee replacement in a consecutive series of 4253 patients [Part A: Total hip replacement]
The incidence of fatal pulmonary embolism after primary hip and knee replacement in a consecutive series of 4253 patients [Part B: Total knee replacement]
A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation [Total knee replacement]
A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial [Total hip replacement]
A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial [Total knee replacement]
A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation [Total hip replacement]
A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty.2001
A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty.2000
Thromboprophylaxis and death after total hip replacement.1996
A meta-analysis of methods to prevent venous thromboembolism following total hip replacement.1994
Prophylactic agents for venous thrombosis in elective hip surgery. Meta-analysis of studies using venographic assessment.1993
Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials.2010
Meta-analysis of low molecular weight heparin versus placebo in patients undergoing total hip replacement and post-operative morbidity and mortality since their introduction.-- Not Found --
A comparison of regional and general anaesthesia for total replacement of the hip or knee: a meta-analysis.2009
Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis.2009
Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis.2004
Major bleeding rates after prophylaxis against venous thromboembolism: systematic review, meta-analysis, and cost implications.2004
Superiority of fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points.2004
Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies.2002
Reduction of out-of-hospital symptomatic venous thromboembolism by extended thromboprophylaxis with low-molecular-weight heparin following elective hip arthroplasty: a systematic review.
Optimal low-molecular-weight heparin regimen in major orthopaedic surgery. A meta-analysis of randomised trials.2003
Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures.
Extended thromboprophylaxis with low molecular weight heparin reduces symptomatic venous thromboembolism following lower limb arthroplasty--a meta-analysis.2001
Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials.2001
Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review.2001
Meta-analysis of thromboembolic prophylaxis after total knee arthroplasty.2000
Low molecular weight heparin decreases proximal and distal deep venous thrombosis following total knee arthroplasty. A meta-analysis of randomized trials.1998
Efficacy and cost of low-molecular-weight heparin compared with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty.1993
Low molecular weight heparin in prevention of perioperative thrombosis.
Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis.1992

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