ower extremity venous thromboembolism (VTE), including deep vein thrombosis (DVT) of the leg, is common. 1 The incidence rate for DVT ranges from 88 to 112 per 100 000 person-years. 2 Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event. 3,4 Isolated distal DVT, defined as thrombosis involving 1 or more of the deep calf veins without reaching the popliteal vein, is associated with a 1-year all-cause mortality rate of 4.6 per 100 person-years (95% CI, 3.8-5.7). 5 This review provides an evidence-based update of the diagnosis and therapy of lower extremity DVT. MethodsWe searched PubMed and the Cochrane databases for Englishlanguage studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies, resulting in 2125 retrieved articles (see eAppendix in the Supplement for search terms). We manually searched references of selected articles, reviews, meta-analyses, and practice guidelines. Selected articles were mutually agreed on by the authors. A total of 86 articles (20 randomized clinical trials, 20 systematic reviews and meta-analyses, 33 observational cohort studies, 7 reviews, and 6 guideline documents) were included in the final review. Randomized clinical trials and meta-analyses and information of interest to a general medical readership were prioritized. Risk Factors for VTEMost patients with VTE have multiple risk factors for VTE (Table 1). Risk factors include demographic factors (eg, older age, IMPORTANCE Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event.OBSERVATIONS PubMed and Cochrane databases were searched for English-language studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies. Risk factors for venous thromboembolism (VTE), such as older age, malignancy (cumulative incidence of 7.4% after a median of 19 months), inflammatory disorders (VTE risk is 4.7% in patients with rheumatoid arthritis and 2.5% in those without), and inherited thrombophilia (factor V Leiden carriers with a 10-year cumulative incidence of 10.9%), are associated with higher risk of VTE. Patients with signs or symptoms of lower extremity DVT, such as swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%), should undergo assessment of pretest probability followed by D-dimer testing and imaging with venous ultrasonography. A normal D-dimer level (ie, D-dimer <500 ng/mL) excludes acute VTE when combined with a low pretest probability (ie, Wells DVT score Յ1). In patients with a high pretest probability, the negative predictive value of a D-dimer less than 500 ng/mL is 92%. Consequently, D-dimer cannot be used to exclude DVT without an assessment of pretest probability. Postthrombotic syndrome, defined as persistent symptoms, signs of ch...

Background and Purpose-Although oral anticoagulants (OACs) are highly effective in reducing stroke risk in atrial fibrillation, some patients still sustain stroke despite being on an OAC. Our aim was to identify the risk factors that contribute to stroke risk in atrial fibrillation, although patients were taking OACs in a clinical trial setting. Methods-We identified contemporary clinical trials that investigated OACs in patients with atrial fibrillation. Event rates per year from each study and pooled event rates and relative risks, all with a 95% confidence interval, were calculated. Statistical heterogeneity was assessed using the I 2 test. Results-Six trials were included in the meta-analysis, with a total of 58 883 patients randomized. Characteristics associated with a higher relative risk of stroke while on an OAC included age ≥75 years (relative risk,

Background and Purpose-Guidelines advocate anticoagulant treatment to all patients with atrial fibrillation and concomitant diabetes mellitus. The potential refinement to thromboembolic risk stratification that may spring from subdividing diabetes mellitus is unexplored. The purpose was to investigate duration of diabetes mellitus as a predictor of thromboembolism and anticoagulant-related bleeding in patients with atrial fibrillation. Methods-Using nationwide Danish registries, we identified all patients discharged from hospital with an incident diagnosis of atrial fibrillation from 2000 to 2011. Hazard ratios with 95% confidence intervals for thromboembolism and bleeding according to years of diabetes mellitus duration in categories (0-4, 5-9, 10-14, and ≥15) and as a continuous variable using cubic splines were calculated by Cox regression. Results-The study population comprised 137 222 patients with atrial fibrillation, of which 12.4% had diabetes mellitus.Compared with patients without diabetes mellitus and after adjustment for anticoagulant treatment and CHA 2 DS 2 -VASc components (congestive heart failure, hypertension, age, previous stroke, vascular disease, and sex), the risk of thromboembolism was lowest in the 0 to 4 years duration category (hazard ratio, 1.11; 95% confidence interval, 1.03-1.20), and highest in the longest duration category of ≥15 years (hazard ratio, 1.48; 95% confidence interval, 1.29-1.70). When analyzed as a continuous variable, duration of diabetes mellitus was associated with risk of thromboembolism in a dose-response-dependent manner, but not with a higher risk of bleeding during anticoagulant treatment. Conclusions-In patients with atrial fibrillation, longer duration of diabetes mellitus was associated with a higher risk of thromboembolism, but not with a higher risk of anticoagulant-related bleeding. Considering the critical balance between preventing thromboembolism and avoiding bleeding, longer duration of diabetes mellitus may favor initiation of anticoagulant therapy.

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The Khorana score is recommended for guiding primary venous thromboembolism prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored competing risk of death, hereby potentially overestimating venous thromboembolism risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated six-month cumulative incidence of venous thromboembolism stratified by Khorana levels. Analyses were conducted with and without considering death as competing risk using the Kaplan-Meier method versus the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40,218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1-2) and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding six-month risks of venous thromboembolism were 1.5% (95% CI 1.3-1-7), 2.8% (95% CI 2.6-3.1), and 4.1% (95% CI 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), six-month risk was 3.6% (95% CI 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to risk of venous thromboembolism, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials.