Venous Thrombosis: Risk Factors and Management

During the past 2 decades, the diagnostic and therapeutic approach to deep vein thrombosis (DVT) has greatly evolved. First, the assessment of the clinical probability has gained wide acceptance. Second, novel noninvasive diagnostic tools such as venous compression ultrasonography and D-dimer measurement have become available, drastically reducing the need for invasive tools such as phlebography. Third, new anticoagulant drugs, in particular low-molecular-weight heparins (LMWHs), have become available and have made DVT treatment a lot easier by allowing out-ofhospital management. Several diagnostic algorithms, based on the assessment of clinical probability, D-dimer measurement and venous compression ultrasonography, have shown to be safe in management studies. In addition to improvements in diagnostic algorithms and anticoagulant treatment, compression therapy by elastic stockings to diminish the prevalence of the postthrombotic syndrome has been validated in prospective studies. The dilemma of the need or no need for looking for and treating isolated calf DVT with anticoagulants remains a controversial issue, as do the optimal length and intensity of anticoagulation. In the near future, the emergence of several new, totally synthetic, orally active anticoagulant compounds, such as direct thrombin or factor Xa inhibitors that are presently being tested in clinical studies, could profoundly change the therapeutic approach to DV

Direct oral anticoagulants in the treatment and long-term prevention of venous thrombo-embolism

Direct oral anticoagulants (DOACs) specifically target factor IIa or Xa and represent a major step forward in the treatment of acute- and long-term prevention of venous thrombo-embolism (VTE). They are at least as effective and as safe as conventional therapy (heparins and vitamin-K inhibitors) and have practical advantages, such as fixed dosing and no need for laboratory monitoring. These antithrombotic agents introduce a new paradigm for the day-to-day management of VTE. Direct oral anticoagulants should streamline the management of most patients with VTE and will facilitate care in the outpatient setting. Nevertheless, it remains uncertain how to select specific DOACs for particular profiles of patients, and the optimal management of bleeding complications is evolvin

Nicotine induced haemodynamic changes during cigarette smoking and nicotine gum chewing: a placebo controlled study in young healthy volunteers

Because cigarette smoking is a definite risk for the development of cardiovascular disease and nicotine induced vasoconstriction may be a possible pathogenetic factor the haemodynamic effects of smoking cigarettes with high or low nicotine content were compared with those induced by chewing nicotine gum in a placebo controlled, crossover study in six healthy volunteers. The three stimuli induced similar increases in heart rate (about 20%) and systolic blood pressure (about 7%) and a decrease in digital blood flow. Although the mean haemodynamic changes parallelled the mean plasma nicotine concentration increases, no correlation was found between them when the individual values were considered. It is concluded that the nicotine induced haemodynamic changes probably occur as a result of the (local) release of vasoactive mediators such as adrenaline or noradrenaline after a threshold plasma nicotine concentration has been reached. Such a threshold may explain the large interindividual variability in susceptibility to smoking induced cardiovascular disease

Swiss results from a global observational study of venous thromboembolism risk and prophylaxis use in the acute care hospital setting: analysis from the ENDORSE study

BACKGROUND: The aim of the present analysis from the epidemiologic international day for the evaluation of patients at risk for venous thromboembolism (VTE) in the acute hospital care setting (ENDORSE) study was to evaluate the prevalence of VTE risk in acute care hospitals and the proportion of at-risk medical and surgical patients who receive recommended prophylaxis in Switzerland. METHODS: All patients (age \u3eor=40 years) admitted to a medical ward or those (age \u3eor=18 years) admitted to a surgical ward in ten randomly selected Swiss hospitals were assessed for risk of VTE. The 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines were used to assess VTE risk and to determine whether patients were receiving recommended thromboprophylaxis. RESULTS: 2000 patients were eligible; of these 1153 (58%) were in surgical wards, and 847 (42%) in medical wards. According to the ACCP criteria, the proportion of surgical patients at VTE risk was similar in Switzerland (68%, between hospital range 48-86%) in comparison to the global ENDORSE study (64%) (p = 0.296). The rate of at-risk medical patients was lower in Switzerland (21%, range 3-44%) than in the global study (42%) (p \u3c0.001). The proportion of at-risk surgical patients with ACCP-recommended VTE prophylaxis was higher in Switzerland (81%, between-hospital range 76-93%) than in the global study (59%) (p \u3c0.001). Among medical patients at risk, the use of recommended thromboprophylaxis was higher in Switzerland (61%, between-hospital range 0-84%) than in the global ENDORSE (40%) (p \u3c0.001). However 56% of the patients with cancer, 41% with major trauma, and 29% undergoing vascular surgery did not receive any recommended prophylaxis. Among surgical patients at risk, the use of ACCP-recommended prophylaxis was lower in academic (77%) vs. non-academic (86%) institutions (p = 0.0025). CONCLUSIONS: In Switzerland, although the rate of recommended thromboprophylaxis is higher than in many countries, it is still improvable in medical patients at risk according to the ACCP guidelines. Consequently, hospital wide strategies for systematic risk factor assessment and implementation of practical tools to ensure appropriate use of prophylaxis in patients at VTE risk are required

Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism : a pooled analysis of the EINSTEIN-DVT and PE randomized studies

Background: Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. Methods: A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. Results: 8282 patients were enrolled. 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 rivaroxaban-treated patients (2.1%) compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66-1.19; pnoninferiority<0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37-0.79; p=0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban was similar compared with standard-therapy. Conclusion: The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups

Uptake of new treatment strategies for deep vein thrombosis: an international audit

Objective. Study of the uptake of new medical technologies provides useful information on the transfer of published evidence into usual practice. We conducted an audit of selected hospitals in three countries (Canada, France, and Switzerland) to identify clinical predictors of low-molecular-weight (LMW) heparin use and outpatient treatment, and to compare the pace of uptake of these new therapeutic approaches across hospitals. Design. Historical review of medical records. Setting and participants. We reviewed the medical records of 3043 patients diagnosed with deep vein thrombosis (DVT) in five Canadian, two French, and two Swiss teaching hospitals from 1994 to 1998. Measures. We explored independent clinical variables associated with LMW heparin use and outpatient treatment, and determined crude and adjusted rates of LMW heparin use and outpatient treatment across hospitals. Results. For the years studied, the overall rates of LMW heparin use and outpatient treatment in the study sample were 34.1 and 15.8%, respectively, with higher rates of use in later years. Many comorbidities were negatively associated with outpatient treatment, and risk-adjusted rates of use of these new approaches varied significantly across hospitals. Conclusion. There has been a relatively rapid uptake of LMW heparins and outpatient treatment for DVT in their early years of availability, but the pace of uptake has varied considerably across hospitals and countrie

Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts

Objectives In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was devised and its usefulness with older patients assessed

Synergistic Effects of Hypofibrinolysis and Genetic and Acquired Risk Factors on the Risk of a First Venous Thrombosis

Frits Rosendaal and colleagues show that the combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options