Is venous thromboprophylaxis necessary in patients undergoing minimally invasive surgery for a gynecologic malignancy?

OBJECTIVES: Current recommendations for the use of venous thromboprophylaxis in patients undergoing minimally invasive surgery (MIS) for a gynecologic malignancy are derived from patients undergoing open surgery. Our objective was to determine the 30-day prevalence of symptomatic venous thromboembolism (VTE) after laparoscopic gynecologic oncology procedures in patients who received no thromboprophylaxis. METHODS: Between January 2006 and September 2013, women who underwent MIS for endometrial, cervical or ovarian cancer at a single institution were included. Data on patient demographics, diagnosis, comorbidities, perioperative characteristics, use of thromboprophylaxis, and diagnosis of VTE were collected retrospectively. RESULTS: Of the 419 patients who underwent MIS for a gynecologic cancer, 352 (84%) received no VTE prophylaxis. At least a total laparoscopic hysterectomy (simple or radical) or pelvic lymph node dissection was performed in 95% of these patients. The median length of surgery was 137 min and 95% of patients were discharged home within 1 day of surgery. The rate of VTE in the 352 untreated patients was 0.57% (1 pulmonary embolism and 1 deep vein thrombosis). There were no VTE diagnosed within 30 days of surgery in the 67 patients who received anticoagulant thromboprophylaxis. CONCLUSION: The rate of VTE is low in patients undergoing minimally invasive surgery for a gynecologic malignancy despite no VTE prophylaxis. The benefits of routine use of VTE prophylaxis in this population are questionable.

Venous Thromboembolism Prevention in Rehabilitation: A Review and Practice Suggestions.

ABSTRACT: Venous thromboembolism is a frequent complication of acute hospital care, and this extends to inpatient rehabilitation. The timely use of appropriate thromboprophylaxis in patients who are at risk is a strong, evidence-based patient safety priority that has reduced clinically important venous thromboembolism, associated mortality and costs of care. While there has been extensive research on optimal approaches to venous thromboembolism prophylaxis in acute care, there is a paucity of high-quality evidence specific to patients in the rehabilitation setting, and there are no clinical practice guidelines that make recommendations for (or against) thromboprophylaxis across the broad spectrum of rehabilitation patients. Herein, we provide an evidence-informed review of the topic with practice suggestions. We conducted a series of literature searches to assess the risks of venous thromboembolism and its prevention related to inpatient rehabilitation as well as in major rehabilitation subgroups. Mobilization alone does not eliminate the risk of venous thromboembolism after another thrombotic insult. Low molecular weight heparins and direct oral anticoagulants are the principal current modalities of thromboprophylaxis. Based on the literature, we make suggestions for venous thromboembolism prevention and include an approach for consideration by rehabilitation units that can be aligned with local practice.

Economic analyses of venous thromboembolism prevention strategies in hospitalized patients: a systematic review.

INTRODUCTION: Despite evidence-based guidelines for venous thromboembolism prevention, substantial variability is found in practice. Many economic evaluations of new drugs for thromboembolism prevention do not occur prospectively with efficacy studies and are sponsored by the manufacturers, raising the possibility of bias. We performed a systematic review of economic analyses of venous thromboembolism prevention in hospitalized patients to inform clinicians and policy makers about cost-effectiveness and the potential influence of sponsorship. METHODS: We searched MEDLINE, EMBASE, Cochrane Databases, ACP Journal Club, and Database of Abstracts of Reviews of Effects, from 1946 to September 2011. We extracted data on study characteristics, quality, costs, and efficacy. RESULTS: From 5,180 identified studies, 39 met eligibility and quality criteria. Each addressed pharmacologic prevention: low-molecular-weight heparins versus placebo (five), unfractionated heparin (12), warfarin (eight), one or another agents (five); fondaparinux versus enoxaparin (11); and rivaroxaban and dabigatran versus enoxaparin (two). Low-molecular-weight heparins were most economically attractive among most medical and surgical patients, whereas fondaparinux was favored for orthopedic patients. Fondaparinux was associated with increased bleeding events. Newer agents rivaroxaban and dabigatran may offer additional value. Of all economic evaluations, 64% were supported by manufacturers of a "new" agent. The new agent had a favorable outcome in 38 (97.4%) of 39 evaluations [95% confidence interval [CI] (86.5 to 99.9)]. Among studies supported by a pharmaceutical company, the sponsored medication was economically attractive in 24 (96.0%) of 25 [95% CI, 80.0 to 99.9)]. We could not detect a consistent bias in outcome based on sponsorship; however, only a minority of studies were unsponsored. CONCLUSION: Low-molecular-weight heparins and fondaparinux are the most economically attractive drugs for venous thromboembolism prevention in hospitalized patients. Approximately two thirds of evaluations were supported by the manufacturer of the new agent; such drugs were likely to be reported as economically favorable.

A pilot study of computed tomography-detected asymptomatic pulmonary filling defects after hip and knee arthroplasties.

We asked what the incidence of asymptomatic filling defects is on routine multidetector computed tomography (MDCT) in primary hip (total hip arthroplasty [THA]) and knee arthroplasties (TKA) patients. We prospectively performed MDCT scans on the first postoperative day for THA (n = 21)/TKA (n = 27). Patients underwent routine postoperative care, and data were collected for symptoms such as tachycardia or shortness of breath. More patients undergoing TKA had positive computed tomography scans than those undergoing THA: 11 (41%) vs 1 (5%), respectively. All patients diagnosed with a filling defect were discharged from the hospital without treatment of symptomatic pulmonary embolism. Our study demonstrates a high rate of abnormal MDCT early after lower extremity arthroplasty, the clinical importance of which may be benign.

The association between anticoagulation and adverse outcomes after a positive SARS-CoV-2 test among older outpatients: A population-based cohort study.

INTRODUCTION: Anticoagulation may improve outcomes in patients with COVID-19 when started early in the course of illness. MATERIALS AND METHODS: This was a population-based cohort study using linked administrative datasets of outpatients aged ≥65 years old testing positive for SARS-CoV-2 between January 1 and December 31, 2020 in Ontario, Canada. The key exposure was anticoagulation with warfarin or direct oral anticoagulants before COVID-19 diagnosis. We calculated propensity scores and used matching weights (MWs) to reduce baseline differences between anticoagulated and non-anticoagulated patients. The primary outcome was a composite of death or hospitalization within 60 days of a positive SARS-CoV-2 test. We used the Kaplan-Meier method and cumulative incidence functions to estimate risk of the primary and component outcomes at 60 days. RESULTS: We studied 23,159 outpatients (mean age 78.5 years; 13,474 [58.2%] female), among whom 3200 (13.8%) deaths and 3183 (13.7%) hospitalizations occurred within 60 days of the SARS-CoV-2 test. After application of MWs, the 60-day risk of death or hospitalization was 29.2% (95% CI 27.4%-31.2%) for anticoagulated individuals and 32.1% (95% CI 30.7%-33.5%) without anticoagulation (absolute risk difference [ARD], -2.9%; p = 0.005). Anticoagulation was also associated with a lower risk of death: 18.6% (95% CI 17.0%-20.2%) with anticoagulation and 20.9% (95% CI 19.7%-22.2%) in non-anticoagulated patients (ARD -2.3%; p = 0.005). CONCLUSIONS: Among outpatients aged ≥65 years, oral anticoagulation at the time of a positive SARS-CoV-2 test was associated with a lower risk of a composite of death or hospitalization within 60 days.

Guidance for Health Care Leaders During the Recovery Stage of the COVID-19 Pandemic: A Consensus Statement.

Importance: The COVID-19 pandemic is the greatest global test of health leadership of our generation. There is an urgent need to provide guidance for leaders at all levels during the unprecedented preresolution recovery stage. Objective: To create an evidence- and expertise-informed framework of leadership imperatives to serve as a resource to guide health and public health leaders during the postemergency stage of the pandemic. Evidence Review: A literature search in PubMed, MEDLINE, and Embase revealed 10 910 articles published between 2000 and 2021 that included the terms leadership and variations of emergency, crisis, disaster, pandemic, COVID-19, or public health. Using the Standards for Quality Improvement Reporting Excellence reporting guideline for consensus statement development, this assessment adopted a 6-round modified Delphi approach involving 32 expert coauthors from 17 countries who participated in creating and validating a framework outlining essential leadership imperatives. Findings: The 10 imperatives in the framework are: (1) acknowledge staff and celebrate successes; (2) provide support for staff well-being; (3) develop a clear understanding of the current local and global context, along with informed projections; (4) prepare for future emergencies (personnel, resources, protocols, contingency plans, coalitions, and training); (5) reassess priorities explicitly and regularly and provide purpose, meaning, and direction; (6) maximize team, organizational, and system performance and discuss enhancements; (7) manage the backlog of paused services and consider improvements while avoiding burnout and moral distress; (8) sustain learning, innovations, and collaborations, and imagine future possibilities; (9) provide regular communication and engender trust; and (10) in consultation with public health and fellow leaders, provide safety information and recommendations to government, other organizations, staff, and the community to improve equitable and integrated care and emergency preparedness systemwide. Conclusions and Relevance: Leaders who most effectively implement these imperatives are ideally positioned to address urgent needs and inequalities in health systems and to cocreate with their organizations a future that best serves stakeholders and communities.

Vena caval filters: current knowledge, uncertainties and practical approaches.

PURPOSE OF REVIEW: Inferior vena caval (IVC) interruption has been used as a method to prevent pulmonary embolism since the 1940s. Despite an exponential increase in IVC filter use in both the treatment and prophylaxis of venous thromboembolism, there is little evidence to support current practice. This review will discuss controversies related to IVC filters and will provide a practical approach to their use. RECENT FINDINGS: Current practice guidelines recommend that IVC filters be placed in patients with acute proximal deep vein thrombosis and a contraindication to anticoagulation. We do not recommend IVC filters as primary thromboprophylaxis, even for high-risk surgical or trauma patients. We also do not believe that there is a role for IVC filters in cancer patients with venous thromboembolism when traditional anticoagulation has failed. IVC filters have been shown to be associated with an increased risk of recurrent deep vein thrombosis. SUMMARY: IVC filters are indicated in only a small proportion of patients who have venous thromboembolism. In these situations, retrievable filters are recommended. Anticoagulation should be initiated after filter placement as soon as it is safe to do so and the filter should then be removed shortly thereafter.

Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the "Grades of Recommendation" chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis > 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).

The TOronto ThromboProphylaxis Patient Safety Initiative (TOPPS): A cluster randomised trial.

BACKGROUND: Although venous thromboembolism (VTE) is one of the most common and most preventable complications of hospital stay, review of the literature demonstrates large evidence-care gaps for VTE prevention. OBJECTIVES: This study aimed to determine if a multi-component quality improvement (QI) strategy, including the support of hospital leadership, use of order sets, audit and feedback, and active pharmacy involvement, could increase the use of appropriate thromboprophylaxis in patients hospitalized for hip fracture surgery (HFS), major general surgery (MGS) and acute medical illness (MED). METHODS: TOPPS was a cluster randomized trial involving eight hospitals. After a baseline data collection phase, one of the three patient groups at each site was randomized to the targeted QI intervention while the other two groups served as controls. In the next phase, an additional patient group at each site was randomized to the intervention while the third group remained controls. Standardized chart audits were conducted to assess the rates of appropriate thromboprophylaxis use. RESULTS: At baseline, the rates of appropriate thromboprophylaxis were 79% in HFS, 43% in MGS and 31% in MED. By the end of phase 3, 89% of HFS, 65% of MGS and 70% of MED patients were receiving appropriate prophylaxis. Improvement was greater in the intervention groups compared to controls (85% vs. 76% in HFS; 67% vs. 54% in MGS; 64% vs. 62% in MED) and this difference reached significance in the MGS group (p = 0.048). CONCLUSIONS: Use of a multi-component intervention can be effective in improving the appropriate use of thromboprophylaxis.

Development and evaluation of a continuing pharmacy education (CPE) program in thrombosis management.

BACKGROUND AND PURPOSE: A continuing education (CE) course in thrombosis management for pharmacists was developed through the Office of Continuing Professional Development (CPD) at the University of Toronto to address pharmacists' needs for the knowledge and skills to provide care to patients receiving anticoagulants. This article describes the development of the course as well as the evaluation designed to assess its impact on pharmacists' knowledge, attitudes, and changes in practice. EDUCATIONAL ACTIVITY AND SETTING: A three-day course was developed. Outcomes were evaluated using a feedback questionnaire, pre- and post-session quizzes and semi-structured interviews conducted six months after course completion. Participant satisfaction, knowledge acquisition and perceived change in knowledge, skills and practice were evaluated. FINDINGS: Thirty-seven pharmacists enrolled in the program, 21 of whom participated in a semi-structured interview. More than 90% reported that the program exceeded their expectations. Pharmacists' knowledge in thrombosis care improved significantly after each day of the course. Participants felt the greatest benefits of the program were increases in knowledge and confidence and the opportunity to network. The case-based discussions and practical tips gained from experts and peers were highly ranked. Participants strongly agreed that they were applying what they learned in the course to clinical practice, and they provided numerous examples of how their practice changed because of the program. DISCUSSION AND SUMMARY: The development of this CE course demonstrates application of best practices in continuing education. The evaluation of the program suggests that a CE course in thrombosis improves pharmacist knowledge, confidence and ability to incorporate what was learned into practice. This course design and evaluation can serve as a model for other CE courses for pharmacists as this field continues to grow and encourages thoughtful use of theoretical principles and well-designed evaluation for continual improvement of CE.

Functional and Exercise Limitations After a First Episode of Pulmonary Embolism: Results of the ELOPE Prospective Cohort Study.

BACKGROUND: We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea. METHODS: One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (Vo2 peak) < 80% at 1-year CPET. RESULTS: At 1 year, 40 of 86 patients (46.5%) had percent predicted Vo2 peak < 80% on CPET, which was associated with significantly worse generic health-related QoL (HRQoL), PE-specific HRQoL and dyspnea scores, and significantly reduced 6MWD at 1 year. Predictors of the primary outcome included male sex (relative risk [RR], 3.2; 95% CI, 1.3-8.1), age (RR, 0.98; 95% CI, 0.96-0.99 per 1-year age increase), BMI (RR 1.1; 95% CI, 1.01-1.2 per 1 kg/m2 BMI increase), and smoking history (RR, 1.8; 95% CI, 1.1-2.9), as well as percent predicted Vo2 peak < 80% on CPET at 1 month (RR, 3.8; 95% CI,1.9-7.2), and 6MWD at 1 month (RR, 0.82; 95% CI, 0.7-0.9 per 30-m increased walking distance). Baseline or residual clot burden was not associated with the primary outcome. Mean PFT and echocardiographic results (pulmonary artery pressure, right and left ventricular systolic function) at 1 year were similarly within normal limits in both patients with exercise limitations and those without such limitations. CONCLUSIONS: Almost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov.

Venous Thromboembolism Prophylaxis in Liver Surgery.

BACKGROUND: At a recently concluded Americas Hepato-Pancreato-Biliary Association Annual Meeting, a Clinical Practice Guidelines Conference Series was convened with the topic focusing on Venous Thromboembolism (VTE) Prophylaxis in Liver Surgery. The symposium brought together hepatobiliary surgeons from three continents as well as medical experts in hematology and coagulation. METHODS: The content of the discussion included literature reviews, evaluation of multi-institutional VTE outcome data, and examination of practice patterns at multiple high-volume centers. RESULTS: Literature review demonstrated that, within gastrointestinal surgery, liver resection patients are at particularly high-risk for VTE. Recent evidence clearly indicates a direct relationship between the magnitude of hepatectomy and postoperative VTE rates, however, the PT/INR does not accurately reflect the coagulation status of the post-hepatectomy patient. Evaluation of available data and practice patterns regarding the utilization and timing of anticoagulant VTE prophylaxis led to recommendations regarding preoperative and postoperative thromboprophylaxis for liver surgery patients. CONCLUSIONS: This conference was effective in consolidating our knowledge of coagulation abnormalities after liver resection. Based on the expert review of the available data and practice patterns, a number of recommendations were developed.

Anticoagulant use in patients with chronic renal impairment.

Patients with renal failure have an increased risk of both thrombotic and bleeding complications. A number of antithrombotic drugs undergo renal clearance. Therefore, estimation of renal function is necessary when prescribing these drugs to patients with renal dysfunction. Pharmacokinetic and clinical data in patients with chronic renal impairment are limited for several anticoagulants, and adequate administration information is often absent. Dose adjustment of anticoagulants may be indicated when the creatinine clearance falls below 30 mL/min. Unfractionated heparin, argatroban, and vitamin K antagonists generally do not require dose adjustment with renal dysfunction. However, smaller doses of warfarin may be required to achieve a particular target international normalized ratio. Close monitoring of anticoagulation is recommended when argatroban or high doses of unfractionated heparin are administered in patients with severe chronic renal impairment. Low-molecular weight heparins, danaparoid sodium, hirudins, and bivalirudin all undergo renal clearance. Lower doses and closer anticoagulation monitoring may be advisable when these agents are used in patients with chronic renal failure. We recommend that fondaparinux sodium and ximelagatran (not yet licensed) be avoided in the presence of severe renal impairment and be used with caution in patients with moderate renal dysfunction. While acknowledging the lack of pharmacokinetic data, this review provides specific recommendations for the use of anticoagulants in patients with chronic renal impairment.

Deep venous thrombosis: clinically silent in the intensive care unit.

PURPOSE: The reliability of clinical signs and the physical examination in the evaluation of deep venous thrombosis (DVT) in the critically ill is unknown. The purpose of this study was to determine the diagnostic properties of clinical examination for signs of DVT in a cohort of medical-surgical intensive care unit (ICU) patients using screening compression ultrasonography as a reference standard. MATERIALS AND METHODS: We prospectively included patients older than 18 years with an expected length of ICU stay of more than 72 hours. Patients underwent bilateral lower limb screening compression ultrasound twice weekly and structured physical examination twice weekly by 2 independent trained research coordinators blinded to the ultrasonography results. We classified patients according to 2 methods: method 1, a DVT Risk Stratification System of 3 categories and method 2, a DVT Risk Score, both of which use the history and physical examination to stratify patients for their risk of DVT. RESULTS: We included 239 patients in our study, 32 of whom had DVT based on the results of their compression ultrasound. We excluded 7 patients with DVT on ICU admission and 2 who did not undergo any structured examinations. We matched controls with cases (9:1) based on duration of ICU stay. Cases and controls were then allocated to low, moderate, and high risk strata for DVT. Using method 1, the area under the receiver operating characteristic curve (AUC) was 0.57 (95% CI, 0.33-0.78, P = .01). Using method 2, the AUC was 0.59 (95% CI, 0.42-0.75, P = .02). An AUC of 1.0 indicates an ideal test, and AUC of 0.50 indicates a test with no diagnostic utility. CONCLUSIONS: The history and physical examination for DVT are not useful in detecting lower limb DVT in the ICU.

Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors.

OBJECTIVE: The purpose of this study is to describe the prevalence, to analyze the incidence and independent risk factors for thrombocytopenia, and to examine the impact of thrombocytopenia developing in the intensive care unit (ICU) on patient outcome in a well-defined cohort of critically ill patients in a medical-surgical ICU. MATERIALS AND METHODS: As part of a prospective cohort study examining the frequency and clinical importance of venous thromboembolism in the ICU, we enrolled consecutive patients older than 18 years expected to be in the ICU for more than 72 hours. Exclusion criteria were an admitting diagnosis of trauma, orthopedic surgery or cardiac surgery, pregnancy, and life support withdrawal. Patients had platelet counts performed as directed by clinical need. We defined thrombocytopenia as a platelet count of less than 150 x 10(9)/L and severe thrombocytopenia as a platelet count of less than 50 x 10(9)/L. Protocol-directed care included routine thromboprophylaxis and twice weekly screening ultrasonography of the legs. Patients were followed to hospital discharge. RESULTS: Of the 261 enrolled patients, 121 (46%, 95% confidence interval [CI], 40%-53%) had thrombocytopenia (62 on ICU admission and 59 acquired during their ICU stay). Patients who developed a platelet count less than 150 x 10(9)/L during their ICU stay had higher ICU and hospital mortality (P = .03 and .005, respectively), required longer mechanical ventilation (P = .05), and were more likely to receive platelets (P < .001), fresh frozen plasma (P = .005), and red blood cell transfusions (P = .004) than patients who did not develop thrombocytopenia. The only independent risk factors for thrombocytopenia developing during the ICU stay were administration of nonsteroidal anti-inflammatory drugs before ICU admission (hazard ratio, 2.8; 95% CI, 1.3-6.0) and dialysis during the ICU stay (hazard ratio, 3.1; 95% CI, 1.2-7.8). Of the 33 patients who underwent 36 tests for heparin-induced thrombocytopenia, none tested positive. CONCLUSIONS: We found that about 50% of the patients admitted to the ICU had at least one platelet count of less than 150 x 10(9)/L during their ICU stay. Patients who developed thrombocytopenia were more likely to die, required longer duration of mechanical ventilation, and were more likely to require blood product transfusion. Heparin-induced thrombocytopenia was frequently suspected but did not develop in these critically ill patients.

A double-blind, randomized controlled trial of the prevention of clinically important venous thromboembolism after isolated lower leg fractures.

BACKGROUND: Among patients with isolated below-knee fractures, previous studies have detected asymptomatic deep vein thrombosis in 10%-40% using contrast venography. However, the clinical relevance of these thrombi is unknown; there is considerable uncertainty about the risk: benefit of routine thromboprophylaxis and clinical practice guidelines differ in their recommendations. METHODS: In this multicenter, double-blind trial, 265 patients with isolated lower leg fractures requiring surgery were randomized to subcutaneous dalteparin 5000 units or matching placebo once daily for 2 weeks with bilateral Doppler ultrasound (DUS) of the proximal leg veins on postoperative day 14±2 and 3-month follow-up. The primary effectiveness outcome was clinically important venous thromboembolism (CIVTE), defined as the composite of symptomatic venous thromboembolism within 3 months after surgery and asymptomatic proximal deep vein thrombosis on DUS. The primary safety outcome was major bleeding. RESULTS: Two hundred fifty-eight patients (97%) were included in the primary outcome analysis for effectiveness (130: dalteparin; 128: placebo). Incidence of CIVTE in the dalteparin and placebo groups was 1.5% and 2.3%, respectively (absolute risk reduction, 0.8%; 95% confidence interval, -2.0 to 3.0). There were no fatal pulmonary emboli or major bleeding. CONCLUSIONS: The overall incidence of CIVTE after surgically repaired, isolated tibia, fibula, and ankle fractures was low (1.9%; 95% confidence interval, 0.7-4.7), with no observed differences between dalteparin and placebo either for CIVTE or safety. Recruitment was stopped at the first interim analysis. This study also demonstrates the substantial discrepancy in venous thromboembolism rates between trials that use venographic outcomes compared with more clinically relevant outcomes. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following. We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A). For moderate-risk general surgery patients, we recommend prophylaxis with low-dose unfractionated heparin (LDUH) (5,000 U bid) or low-molecular-weight heparin (LMWH) [< or = 3,400 U once daily] (both Grade 1A). For higher risk general surgery patients, we recommend thromboprophylaxis with LDUH (5,000 U tid) or LMWH (> 3,400 U daily) [both Grade 1A]. For high-risk general surgery patients with multiple risk factors, we recommend combining pharmacologic methods (LDUH three times daily or LMWH, > 3,400 U daily) with the use of graduated compression stockings and/or intermittent pneumatic compression devices (Grade 1C+). We recommend that thromboprophylaxis be used in all patients undergoing major gynecologic surgery (Grade 1A) or major, open urologic procedures, and we recommend prophylaxis with LDUH two times or three times daily (Grade 1A). For patients undergoing elective total hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or adjusted-dose vitamin K antagonist (VKA) [international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0] (all Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1C+), VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 2B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty, or HFS receive thromboprophylaxis for at least 10 days (Grade 1A). We recommend that all trauma patients with at least one risk factor for VTE receive thromboprophylaxis (Grade 1A). In acutely ill medical patients who have been admitted to the hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, we recommend prophylaxis with LDUH (Grade 1A) or LMWH (Grade 1A). We recommend, on admission to the intensive care unit, all patients be assessed for their risk of VTE. Accordingly, most patients should receive thromboprophylaxis (Grade 1A).

Symptomatic venous thromboembolism uncommon without thromboprophylaxis after isolated lower-limb fracture: the knee-to-ankle fracture (KAF) cohort study.

BACKGROUND: The prevalence of deep vein thrombosis as demonstrated by routine venography in patients with distal lower-extremity injury requiring cast immobilization or surgery is 10% to 40%. These deep vein thromboses are usually asymptomatic and distal, and the need for thromboprophylaxis in these patients is not known. METHODS: We conducted a multicenter prospective cohort study to define the prevalence of symptomatic venous thromboembolism in patients with a tibial, fibular, or ankle fracture (treated nonoperatively) or a patellar or foot fracture (treated operatively or conservatively). Consecutive patients were enrolled at five Ontario, Canada, hospitals within ninety-six hours after injury, and they were followed with a telephone interview at two, six, and twelve weeks. Thromboprophylaxis was not allowed. Suspected venous thromboembolism was investigated in a standardized manner. RESULTS: From August 2002 to June 2005, 1200 patients were enrolled, and a three-month follow-up was completed for 98% of them. Eighty-two percent of the patients were treated with cast or splint immobilization for an average (and standard deviation) of 42 ± 32 days. Overall, seven patients (0.6%; 95% confidence interval [CI] = 0.2% to 1.2%) had symptomatic, objectively confirmed venous thromboembolism. Two of them had proximal deep vein thrombosis; three, calf deep vein thrombosis; and two, pulmonary embolism. There were no fatal pulmonary emboli. CONCLUSIONS: Symptomatic venous thromboembolism is an infrequent complication after fractures of the distal part of the lower limb requiring cast immobilization and managed without thromboprophylaxis. Given these estimates of symptomatic venous thromboembolism, the risk-benefit ratio and cost-effectiveness of routine anticoagulant prophylaxis are unlikely to be favorable for these patients. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.