Management of epistaxis associated with oral antithrombotic drugs in emergency department and impact on prescription thereafter.

OBJECTIVES: To describe management, and to assess factors associated with antithrombotic prescription thereafter in patients who had epistaxis referred to emergency department (ED). DESIGN: Prospective cohort study. From EDs, clinical, biological and hospital data were collected. The clinical database was linked to the French Health Insurance Database where we retrieved antithrombotic drug deliveries in a 3-month period before and after referral. SETTING: Multicentric population-based cohort study within five well-defined areas. PARTICIPANTS: We considered 306 patients referred for epistaxis with a stable oral antithrombotic regimen before referral. MAIN OUTCOME MEASURES: We considered management, hospital outcome and case fatality. Antithrombotic prescription in a 3-month follow-up period was categorised into three classes: no change, class change, or discontinuation. During follow-up, hospitalisation for epistaxis or ischaemic events was searched. RESULTS: Among 306 adult individuals (mean age: 76 years), 166 took oral anticoagulant and 140 an antiplatelet drug. Blood transfusion was needed in 13.7% of patients and anterior packing alone in 61%. Half of the patients were hospitalised; 301 were discharged alive. Considering antithrombotic prescription thereafter we observed no change in 219 patients (72.8%), class changes in 47 patients (15.6%) and discontinuation in 35 patients (11.6%). We identified four independent predictors for antithrombotic prescription: hospitalisation (vs. returning home, p = .05), age (p = .03), haemoglobin level (p = .03) and oral anticoagulant (vs. antiplatelet agent, p < .001). During the 3 months following discharge, 2 thrombotic and 15 bleeding events were identified. CONCLUSIONS: Epistaxis referred to emergency department had an impact on subsequent antithrombotic prescription. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02886533.

Predictors of Recurrent Venous Thromboembolism or Arterial Thrombotic Events during and after Anticoagulation for a First Venous Thromboembolism.

After first episodes of venous thromboembolism (VTE), patients are at increased risk of recurrent VTE and arterial thrombotic events (ATE) compared with the general population, two disorders that are influenced by anticoagulation. However, risk factors of these conditions occurring during and after anticoagulation are little described. Using cause-specific hazard regression models, we aimed to determine risk factors of the composite outcome recurrent VTE/ATE, and separately recurrent VTE or ATE, during and after anticoagulation in patients with first episodes of VTE from a prospective cohort. Hazard ratios (HRs) are given with 95% confidence intervals (CIs). A total of 2,011 patients treated for at least 3 months were included. A total of 647 patients had recurrent VTE/ATE (incidence: 4.69% per patient-years) during overall follow-up (median: 92 months). Of these events, 173 occurred during anticoagulation (incidence: 3.67% per patient-years). Among patients free of events at the end of anticoagulation, 801 had a post-anticoagulation follow-up ≥3 months; and 95 had recurrent VTE/ATE (incidence: 1.27% per patient-years). After adjustment for confounders, cancer-associated VTE (HR: 2.64, 95% CI: 1.70-4.11) and unprovoked VTE (HR: 1.95, 95% CI: 1.35-2.81) were the identified risk factors of recurrent VTE/ATE during anticoagulation (vs. transient risk factor-related VTE). Risk factors of recurrent VTE/ATE after anticoagulation included 50 to 65 years of age (vs. < 50, HR: 1.99, 95% CI: 1.04-3.81), older than 65 years (vs. < 50, HR: 5.28, 95% CI: 3.03-9.21), and unprovoked VTE (vs. transient risk factor-related VTE, HR: 2.06, 95% CI: 1.27-3.34). Cancer-associated VTE and unprovoked VTE are the main risk factors of recurrent VTE/ATE during anticoagulation, while older age and unprovoked VTE mainly predict the risk of these events after anticoagulation.

Risk Factors of Cardiovascular Death after Venous Thromboembolism: Results from a Prospective Cohort Study.

BACKGROUND: Cardiovascular deaths (CVDTs) are more frequent in patients with venous thromboembolism (VTE) than in the general population; however, risk factors associated with this increased risk of CVDT in patients with VTE are not described. METHODS: To determine the risk factors of CVDT in patients with VTE from a multicenter prospective cohort study, Fine and Gray subdistribution hazard models were conducted. RESULTS: Of the 3,988 included patients, 426 (10.7%) died of CVDT during a median follow-up of 5 years. The risk factors of CVDT after multivariate analyses were: age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 3.22, 95% confidence interval [CI]: 1.67-6.62), age >65 years (vs. <50 years, HR: 7.60, 95% CI: 3.73-15.52), cancer-associated VTE (vs. transient risk factor-related VTE, HR: 1.73, 95% CI: 1.15-2.61), unprovoked VTE (vs. transient risk factor-related VTE, HR: 1.42, 95% CI: 1.02-2.00), past tobacco use (vs. never, HR: 1.43, 95% CI: 1.06-1.94), current tobacco use (vs. never, HR: 1.87, 95% CI: 1.15-3.01), hypertension (HR: 2.11, 95% CI: 1.51-2.96), chronic heart failure (HR: 2.28, 95% CI: 1.37-3.79), chronic respiratory failure (HR: 1.72, 95% CI: 1.02-2.89), and atrial fibrillation (HR: 1.67, 95% CI: 1.06-2.60). The risk of CVDT was significantly reduced with direct oral anticoagulants (vs. vitamin-K antagonists) and with longer duration of treatment (>3 months). CONCLUSION: Risk factors of CVDT after VTE include some traditional cardiovascular risk factors and other risk factors that are related to characteristics of VTE, and patients' comorbidities.

Risk Factors for Major Adverse Cardiovascular Events and Major Adverse Limb Events after Venous Thromboembolism: A Large Prospective Cohort Study.

BACKGROUND: There is an increased risk of arterial events including major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after venous thromboembolism (VTE). However, their risk factors remain little explored. METHODS: We aimed to determine the risk factors for MACE (acute coronary syndrome/stroke/cardiovascular death) and MALE (limb ischemia/critical limb ischemia/non-traumatic amputation/any limb revascularization) after VTE. Competing risk models (Fine-Gray) were used in a multicenter prospective cohort of 4,940 patients (mean age: 64.6 years and median follow-up: 64 months). RESULTS: MACE occurred in 17.3% of participants (2.35% per patient-years) and MALE in 1.7% (0.27% per patient-years). In multivariable analysis, the identified risk factors for MACE were the age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 2.00, 95% confidence interval [CI]: 1.38-2.91), age >65 years (vs. <50 years, HR 4.85, 95% CI: 3.35-7.02), pulmonary embolism + deep vein thrombosis (DVT) (vs. isolated-DVT, HR: 1.25, 95% CI: 1.02-1.55), unprovoked-VTE (vs. transient risk factor associated-VTE, HR: 1.29, 95% CI: 1.04-1.59), current tobacco use (vs. never, HR: 1.45, 95% CI: 1.07-1.98), hypertension (HR: 1.61, 95% CI: 1.30-1.98), past history of symptomatic atherosclerosis (HR: 1.52, 95% CI: 1.17-1.98), heart failure (HR: 1.71, 95% CI: 1.21-2.42), atrial fibrillation (HR: 1.55, 95% CI: 1.15-2.08), and vena cava filter insertion (HR: 1.46, 95% CI: 1.03-2.08). The identified risk factors for MALE were the age of 50-65 years (vs. <50 years, HR: 3.49, 95% CI: 1.26-9.65) and atrial fibrillation (HR: 2.37, 95% CI: 1.15-4.89). CONCLUSIONS: Risk factors for MACE and MALE after VTE included some traditional cardiovascular risk factors, patient's comorbidities, and some characteristics of VTE.

Risk factors of arterial thrombotic events after unprovoked venous thromboembolism, and after cancer associated venous thromboembolism: A prospective cohort study.

INTRODUCTION: The increased risk of arterial thrombotic (ATE) after VTE, particularly when they are unprovoked or cancer-associated has been established. However, the risk factors of ATE after these VTE remain unclear. MATERIAL AND METHODS: Using cause-specific hazard regression models, we determined risk factors of ATE (myocardial infarction, ischemic stroke, acute limb ischemia, digestive tract ischemia, or renal ischemia) in 2242 patients with unprovoked VTE and in 914 patients with cancer-associated VTE from a multi-center prospective cohort. RESULTS: Of patients with unprovoked-VTE, 174 developed ATE (7.8%, incidence: 1.26 per 100 patient-years) during follow-up (median: 68 months). Among patients with cancer-associated VTE, 57 developed ATE (6.2%, incidence: 1.98 per 100 patient-years) during follow-up (median: 30 months). After multivariable analysis, the identified risk factors of ATE in patients with unprovoked-VTE were age > 65 years (vs. <50 years, HR 2.59, 95% CI: 1.56-4.29), past history of symptomatic atherosclerosis (HR 2.11, 95% CI: 1.40-3.19), and treatment with low molecule weight heparin (vs. vitamin K antagonists, HR: 2.26, 95% CI: 1.13-4.52). In patients with cancer-associated VTE, the identified risk factors of ATE were: past history of symptomatic atherosclerosis (HR: 3.13, 95% CI: 1.72-5.67), and ongoing anticoagulation at the diagnosis of VTE (HR: 2.77, 95% CI: 1.07-7.22). CONCLUSIONS: The risk of ATE after unprovoked VTE and after cancer-associated VTE, is determined by some classic cardiovascular risk factors and appears to be influenced by anticoagulant treatment introduced for VTE, as well as the presence or absence of ongoing anticoagulation at the diagnosis of VTE.

Hemorrhages in Polycythemia Vera and Essential Thrombocythemia: Epidemiology, Description, and Risk Factors-Learnings from a Large Cohort.

BACKGROUND: The management of myeloproliferative neoplasms (MPNs) is based on the reduction of thrombotic risk. The incidence, impact, and risk factors of bleedings have been less studied. METHODS: All patients with polycythemia vera (n=339) or essential thrombocythemia (n=528) treated in our center are included in OBENE (Observatoire BrEstois des NEoplasies myéloprolifératives) cohort (NCT02897297). Major bleeding (MB) and clinically relevant nonmajor bleeding (CRNMB) occurring after diagnosis were included, except after leukemic transformation. RESULTS: With a median follow-up of 8.3 years, incidence of hemorrhages was 1.85% patient/year, with an incidence of MB of 0.95% patient/year. The 10-year bleeding-free survival was 89%. The most frequent locations were digestive tract, "mouth, nose and throat," and muscular hematoma. The case fatality rate of MB was 25%. The proportion of potentially avoidable postoperative bleeding was remarkable (17.6%). In multivariable analysis, eight risk factors of bleeding were identified: leukocytes >20 G/L at diagnosis (hazard ratio [HR]=5.13, 95% confidence interval [CI]: 1.77-14.86), secondary hemopathies (HR=2.99, 95% CI: 1.27-7.04), aspirin use at diagnosis (HR=2.11, 95% CI: 1.24-3.6), platelet count >1,000 G/L at diagnosis (HR=1.93, 95% CI: 1.11-3.36), history of hemorrhage (HR=1.82, 95% CI: 1.03-3.24), secondary cancers (HR=1.71, 95% CI: 1.01-2.89), atrial fibrillation (HR=1.66, 95% CI: 1.01-2.72), and male sex (HR=1.54, 95% CI: 1.02-2.33). The occurrence of a CRNMB increased the risk of a secondary MB (odds ratio=6.13, 95% CI: 2.86-12.6, p<0.00001). Most patients taking hydroxyurea displayed a nonmacrocytic median corpuscular value in the months preceding bleeding (51.4%). DISCUSSION: The morbidity and mortality of bleedings in MPN should not be underestimated, and patients with platelet count >1,000 G/L and/or leukocytes >20 G/L, and possibly patients who suffered from a CRNMB could benefit from cytoreduction to reducing bleeding risk. Postoperative bleedings represent a substantial proportion of bleeding and could be better prevented.

Risk stratification for predicting recurrent venous thromboembolism after discontinuation of anticoagulation: a post hoc analysis of a French prospective multicentre study.

BACKGROUND: We aimed to validate and to refine current recurrent venous thromboembolism (VTE) risk classification. METHODS: We performed a post hoc analysis of a multicentre cohort including 1881 patients with a first symptomatic VTE prospectively followed after anticoagulation discontinuation. The primary objective was to validate the International Society of Thrombosis and Haemostasis (ISTH) risk classification in predicting recurrence risk. The secondary objective was to evaluate a refined ISTH classification based on the recurrence risk estimate for each individual risk factor. RESULTS: During a 4.8-year median follow-up after anticoagulation discontinuation, symptomatic recurrent VTE occurred in 230 patients (12.2%). Based on the ISTH classification, patients with unprovoked VTE or VTE with minor or major persistent risk factors had a 2-fold increased recurrence risk compared with those with VTE and major transient risk factors. Recurrence risk was not increased in patients with minor transient factors (hazard ratio (HR) 1.31, 95% CI 0.84-2.06). Individual risk factors analysis identified hormone-related VTE (pregnancy: HR 0.26, 95% CI 0.08-0.82; oestrogens: HR 0.25, 95% CI 0.14-0.47) and amyotrophic lateral sclerosis (HR 5.84, 95% CI 1.82-18.70). After reclassification of these factors as major transient for the former and major persistent for the latter, the modified ISTH classification allowed us to accurately discriminate between patients at low risk of recurrence (i.e. with major transient risk factors) and those at high risk of recurrence (i.e. without major transient risk factors). CONCLUSIONS: Among patients who stopped anticoagulation after a first VTE, a refined ISTH classification based on recurrence risk intensity of individual factors allowed discrimination between patients at low recurrence risk, including hormonal exposure in women, and patients at high recurrence risk.

Risk Factors of Arterial Events in Patients with Venous Thromboembolism: A Systematic Review and Meta-Analysis.

BACKGROUND: If recent studies suggested that arterial ischemic events in patients with venous thromboembolism (VTE) are more frequent than in the general population without VTE, whether patients with VTE have different risk factors of arterial events than classic known cardiovascular risk factors remain undefined. Through this systematic review and meta-analysis, we aimed to identify risk factors of arterial ischemic events in patients with VTE. METHODS: We searched PubMed, EMBASE, and Cochrane databases to identify cohort studies published between January 1, 2000, and December 31, 2020, reporting risk factors of arterials ischemic events in patients with VTE. Random-effect models meta-analysis served to get the pooled hazard ratio (HR) and 95% confidence interval (CI) of each risk factor identified. RESULTS: We screened 1,467 records of which 18 were finally included in systematic review and 10 in meta-analyses. Adjusted HR for 9 factors were included in meta-analysis. Male gender (HR: 1.38; 95% CI: 1.28-1.49), diabetes (HR: 1.65; 95% CI: 1.28-2.12), hypertension (HR: 1.38; 95% CI: 1.04-1.84), previous atherothrombotic event (HR: 3.22; 95% CI: 1.12-9.23), chronic kidney disease (HR: 1.41; 95% CI: 1.05-1.88), cancer (HR: 1.72; 95% CI: 1.41-2.09), and unprovoked VTE (HR: 1.88; 95% CI: 1.37-2.57) were the identified risk factors of arterial events in VTE population after meta-analysis. CONCLUSION: Risk factors of arterial events in patients with VTE include usual cardiovascular risk factors and other risk factors that are related to VTE such as cancer and unprovoked VTE.

Acute, major muscular hematoma associated with antithrombotic agents: A multicenter real-world cohort.

BACKGROUND: There is little data on major muscular hematomas and the little there is has mainly focused on patients exposed to oral anticoagulants. OBJECTIVE: To describe the clinical characteristics, management and outcomes of patients admitted to emergency department (ED) for major muscular hematoma associated with an antithrombotic agent, and to identify predictors of in-hospital mortality. PATIENTS AND METHODS: Over a three-year period, all consecutive cases of adult patients admitted to the ED of 5 tertiary care hospitals for major muscular hematoma while exposed to an antithrombotic agent were prospectively collected and medically validated. Clinical and biological data, therapeutic management of the bleeding event, and in-hospital mortality were collected from the medical records and compared across five groups of hematoma locations. Potential confounders were taken in account using a multivariate binomial regression model. RESULTS: Three hundred and seventy-five patients were included (mean age = 81.4 years): 271 were exposed to vitamin K antagonists, 58 to parenteral anticoagulants (heparin, LMWH, fondaparinux), 33 to antiplatelets, and 13 to direct oral anticoagulants. The muscular hematomas were located in the lower limbs (n = 198), the rectus sheath (n = 71), the iliopsoas (n = 45), the upper limbs (n = 33), or elsewhere (n = 28). Reversal therapy was prescribed for 48.5% of patients, red cell transfusions for 63.6%, surgery for 12.3% and embolization for 3.5%. For 84% of patients, hospitalization was required, with a median length of stay of 10 days. Overall, in-hospital mortality was 8.5%. Reversal therapy, the need for intensive care and mortality were significantly more frequent among patients with iliopsoas hematomas. The independent predictors of in-hospital mortality were: decrease in mean arterial pressure (RR = 1.84), decrease in hemoglobin level (RR = 1.37) and the iliopsoas location (RR = 3.06). CONCLUSION: Frail elderly patients with major muscular hematomas linked to antithrombotic agents risk substantial morbidity and in-hospital mortality. The iliopsoas location was the most life-threatening bleeding site. Close observation of this population is warranted to ensure better outcomes.

Hemorrhage in Essential Thrombocythemia or Polycythemia Vera: Epidemiology, Location, Risk Factors, and Lessons Learned from the Literature.

Hemorrhage is a well-known complication of essential thrombocythemia (ET) and polycythemia vera (PV), but evidence-based data on its management and prevention are lacking to help inform clinicians. In this review, appropriate published data from the past 15 years regarding bleeding epidemiology, classification, location, and risk factors are presented and discussed. Research was conducted using the Medline database. The bleeding classifications were heterogeneous among the collected studies. The median incidences of bleeding and major bleeding were 4.6 and 0.79% patients/year, in ET patients and 6.5 and 1.05% patients/year in PV patients, respectively. The most frequent location was the gastrointestinal tract. Bleeding accounted for up to 13.7% of deaths, and cerebral bleeding was the main cause of lethal hemorrhage. Thirty-nine potential risk factors were analyzed at least once, but the results were discrepant. Among them, age >60 years, bleeding history, splenomegaly, myeloproliferative neoplasm subtype, and platelet count should deserve more attention in future studies. Among the treatments, aspirin seemed to be problematic for young patients with ET (especially CALR-mutated ET patients) and anagrelide was also identified as a bleeding inducer, especially when associated with aspirin. Future studies should analyze bleeding risk factors in more homogeneous populations and with common bleeding classifications. More tools are needed to help clinicians manage the increased risk of potentially lethal bleeding events in these diseases.

Impact of bariatric surgery on oral anticoagulants pharmacology, and consequences for clinical practice: a narrative review.

The prevalence of obesity has been steadily increasing in recent years worldwide. At the same time bariatric surgery, the best therapeutic strategy to date in terms of sustainable weight loss and improvement of associated comorbidities has been also increasing. However, these surgeries, whether primarily restrictive or malabsorptive, raise questions about the pharmacology of oral drugs. Among widely used drugs, anticoagulants are the referent therapy to treat some cardiovascular diseases such as atrial fibrillation and venous thromboembolism. How bariatric surgery may impact pharmacological properties of oral anticoagulants, and more specifically, direct oral anticoagulants (DOACs) are difficult to anticipate. In this review, we describe available data concerning the potential impact of bariatric surgery on the pharmacology of oral anticoagulants. The vitamin K antagonists (VKAs) requirements for the same international normalized ratio target are reduced after bariatric surgery. Limited data available for dabigatran 150 mg twice daily indicate a risk of insufficient efficacy in atrial fibrillation after gastric bypass due to probable impaired absorption. Data for rivaroxaban at the prophylactic dose of 10 mg per day suggest no impact of bariatric surgery from 3 days to 8 months post-surgery. However, no conclusive data are available for other anticoagulants or the use of DOACs at therapeutic doses. To date, DOACs are not recommended in patients who have undergone bariatric surgery, because of limited available data. Pending new studies to confirm the predictable pharmacokinetics and safety of DOACs in this population, especially at therapeutic doses, VKAs remain the first option for chronic anticoagulation.

Outcomes of pregnancy after bariatric surgery: results of a French matched-cohort study.

BACKGROUND: While the benefits of bariatric surgery (BS) on pregnancy outcomes have been demonstrated for women compared with matched controls on presurgery body mass index (pB-BMI), data are lacking and those benefits are uncertain compared with matched controls on prepregnancy BMI (pP-BMI). OBJECTIVES: Our study aimed to evaluate outcomes (obstetrical and neonatal) of single pregnancy in women previously exposed to BS compared with women unexposed to BS matched on pB-BMI and pP-BMI. SETTINGS: Retrospective matched cohort study from 2 observational studies of pregnant women conducted in a French administrative county (Finistère). METHODS: From April 1, 2015 to January 31, 2019, pregnant women with previous BS (n = 52) were included and compared with 2 different control groups as follows: group A (n = 104), matched for pB-BMI, age, and parity; and group B (n = 104), matched for pP-BMI, age, and parity. RESULTS: In women exposed to BS, mean age was 27.1 (±4.9) years and pB-BMI was 46.0 (±4.6) kg/m2. Operated women differed significantly from group A but not from group B for pP-BMI (29.4 ± 6.1 versus 45.3 ± 4.5 group A versus 28.6 ± 6.6 group B) and gestational diabetes (12.0% versus 44.0% group A versus 17.0% group B), respectively. In the group of women exposed to BS, birth weight (g) was significantly lower (2960 ± 545 versus 3381 ± 735 group A versus 3310 ± 645 group B) and large-for-gestational-age infants less frequent (0% versus 13% group A versus 8% group B). CONCLUSION: Bariatric surgery reduced risks of excessive fetal growth and gestational diabetes with a trend for a higher risk of small-for-gestational-age, despite matching on pP-BMI suggesting a risk associated to BS and solely to previous surgery-induced weight loss.

Incidence of Cancer after a Second Unprovoked Venous Thromboembolic Event.

Patients with two unprovoked venous thromboembolism (VTE) events could be at high risk for cancer diagnosis and may therefore benefit from extended cancer screening strategies. However, accurate data on the incidence of cancer in this population is lacking. In a prospective cohort study, we followed-up with all patients who experienced two unprovoked symptomatic VTE events that occurred in less than 2 years apart. We estimated the 1-year incidence rate of cancer following the second unprovoked VTE event using the Kaplan-Meier method. Potential predictors for cancer diagnosis were assessed using a Cox proportional hazard regression model. Between May 2000 and December 2013, we included 197 patients with two episodes of symptomatic unprovoked VTE that occurred in less than 2 years apart. Their mean age was 66.2 ± 16.3 years, and 122 (51.8%) were male. Seventeen patients were diagnosed with cancer during the year following the second episode of unprovoked VTE, corresponding to a cumulative incidence rate of 9.19% (95% confidence interval [CI]: 5.81-14.37). The 1-year cumulative incidence rate of cancer was 35.88% (95% CI: 19.75-59.25) in patients with VTE recurrence on anticoagulation, 5.51% (95% CI: 2.9-10.32) among patients with a second episode of unprovoked VTE occurring after stopping anticoagulation and 1.15% (95% CI: 0.16-7.88) when time elapsed between the first and recurrent VTE was > 1 year. Our study suggests that the incidence of cancer in patients with a second episode of unprovoked VTE that occurs off anticoagulation, or > 1 year after the first event, is similar to that of patients with a first unprovoked VTE event.

Risk of venous thromboembolism in association with factor V leiden in cancer patients - The EDITH case-control study.

BACKGROUND: Cancer and factor V Leiden mutation are both risk factors for venous thromboembolism (VTE). Cancer critically increases the thrombotic risk whereas Factor V Leiden is the most common pro-thrombotic mutation. The impact of the factor V Leiden on the risk of VTE in cancer patients remains uncertain. OBJECTIVE: To assess the impact of factor V Leiden mutation in cancer-associated thrombosis. METHODS: The EDITH hospital-based case-control study enrolled 182 patients with cancer and VTE as well as 182 control patients with cancer, matched for gender, age and cancer location, between 2000 and 2012, in the University Hospital of Brest. All cases and controls were genotyped for the factor V Leiden mutation and interviewed with a standardized questionnaire. RESULTS: Twenty one of 182 (11.5%) patients with cancer-associated thrombosis carried the factor V Leiden mutation and 4 of 182 (2.2%) controls with cancer but no venous thrombosis. In multivariate analysis including cancer stage and family history of VTE, cancer patients with factor V Leiden mutation had a seven-fold increased risk of venous thromboembolism (adjusted odds ratio [OR], 7.04; 95% CI, 2.01-24.63). CONCLUSION: The pro-thrombotic Factor V Leiden mutation was found to be an independent additional risk factor for venous thromboembolism in cancer patients and might therefore be considered in the individual thrombotic risk assessment.

Real-world incidence of cancer following a first unprovoked venous thrombosis: Results from the EPIGETBO study.

BACKGROUND: Venous thromboembolism (VTE) can be the first manifestation of cancer; however, the current incidence of malignancy in unselected patients with first unprovoked VTE needs to be confirmed. MATERIAL AND METHODS: Between March 1st, 2013 and February 28th, 2015 we included and followed-up all patients living in the Brest district, France, who were seen in hospitals or the community for a first symptomatic unprovoked VTE event. The primary study outcome was the one-year incidence of cancer. RESULTS: 526 patients, mean age 66.6 ±â€¯18.1 years, 246 (46.8%) men, were included in the study. In the year following VTE, 26 patients were diagnosed with cancer, corresponding to a one-year cumulative incidence of cancer of 5.06% (95% CI 3.47-7.35). Age ≥60, smoking and pulmonary embolism were significantly associated with cancer diagnosis in multivariate analysis. Fifty percent of cancers were patent at the time of VTE diagnosis, mostly detected on CTPA (Computed Tomographic Pulmonary Angiography) performed for pulmonary embolism assessment. After excluding patients with patent cancer at VTE diagnosis, the one-year incidence of cancer was 2.65% (95% CI: 1.55-4.52); in multivariate analysis, only current smoking was independently associated with a significant 5.4-fold increased risk for cancer diagnosis (HR 5.40; 95% CI 1.31-22.27). No cancer was diagnosed in patients aged 50 years or younger. CONCLUSION: The one-year incidence of cancer after a first unprovoked VTE was 5.06%. Half of the cancers were diagnosed during the diagnosis procedure for pulmonary embolism using CTPA.

Non-adherence to treatment with cytoreductive and/or antithrombotic drugs is frequent and associated with an increased risk of complications in patients with polycythemia vera or essential thrombocythemia (OUEST study).

The purpose of this study was to identify the incidence, causes and impact of non-adherence to oral and subcutaneous chronic treatments for patients with polycythemia vera or essential thrombocythemia. Patients receiving cytoreductive drugs for polycythemia vera or essential thrombocythemia were recruited at our institution (Observatoire Brestois des Néoplasies Myéloprolifératives registry). They completed a one-shot questionnaire designed by investigators (Etude de l'Observance Thérapeutique et des Effets Secondaires des Traitements study). Data about complications (thrombosis, transformation and death) at any time in the patient's life (before diagnosis, up until consultation and after the completion of the questionnaire) were collected. Sixty-five (22.7%) of 286 patients reported poor adherence (<90%) to their treatment with cytoreductive drugs and 46/255/18%) also declared non-adherence to antithrombotic drugs. In total, 85/286 patients (29.7%) declared they did not adhere to their treatment. Missing an intake was rare and was mostly due to forgetfulness especially during occupational travel and holidays. Patients who did not adhere to their treatment were characterized by younger age, living alone, having few medications but a high numbers of pills and determining their own schedule of drug intake. Having experienced thrombosis or hematologic evolution did not influence the adherence rate. Non-adherence to oral therapy was associated with a higher risk of phenotypic evolution (7.3 versus 1.8%, P=0.05). For patients treated for polycythemia vera or essential thrombocythemia, non-adherence to cytoreductive and/or antithrombotic therapies is frequent and is influenced by age, habitus and concomitant treatments, but not by disease history or treatment side effects. Phenotypic evolution seems to be more frequent in the non-adherent group.

Performance of 18F-fluorodesoxyglucose positron-emission tomography combined with low-dose computed tomography for cancer screening in patients with unprovoked venous thromboembolism.

PURPOSE: Small series have suggested that Fluorodesoxyglucose Positron-Emission-Tomography with Computed-Tomography (FDG-PET/CT) is feasible to screen for cancer in patients with unprovoked venous thromboembolism (VTE), but without validation in a large population. The aim was to assess diagnostic accuracy indices of FDG-PET/CT for occult cancer diagnosis in patients with unprovoked VTE. MATERIALS AND METHODS: We analysed patients from the FDG-PET/CT group of a randomized trial that compared a screening strategy based on FDG-PET/CT with a limited screening strategy for occult malignancy detection in patients with unprovoked VTE. FDG-PET/CT was interpreted as positive for cancer, as negative or as equivocal. Patients were considered as having cancer on the basis of screening results, or of any test performed during a two-years follow-up period. We ran two sets of analysis, considering patients with equivocal FDG-PET/CT as positive, then as negative for malignancy. RESULTS: Between March 2009, and August 2012, 172 patients were included. FDG-PET/CT was interpreted as positive for malignancy in 10 patients (5.8%), as equivocal in 23 patients (13.4%) and as negative in 139 patients (80.8%). Malignancy was diagnosed in 7/10 (70.0%), 2/23 (8.7%) and 1/139 (0.7%) patients, respectively. Grouping positive and equivocal results, sensitivity and specificity were 90% (95%CI 60% to 98%) and 85% (95%CI 79% to 90%), respectively. Grouping negative and equivocal results, sensitivity and specificity were 70% (95%CI 40% to 89%) and 98% (95%CI 95% to 99%), respectively. CONCLUSION: FDG-PET/CT showed good accuracy for occult cancer screening in patients with unprovoked VTE. Remaining challenges include the need to define specific interpretation criteria in this dedicated population.

Thrombin Generation Measurements in Patients Scheduled for Laparoscopic Bariatric Surgery.

PURPOSE: Obese patients are known to be in an in vitro hypercoagulable state relative to normal-weight patients. Our study aimed to identify markers of enhanced coagulability (endogenous thrombin potential (ETP)) in morbidly obese patients using the thrombin generation (TG) test. MATERIALS AND METHODS: All patients scheduled for laparoscopic bariatric surgery (LBS) between September 1, 2014 and January 31, 2016 were eligible for our prospective study. We used logistic regression to compute the odds ratio (OR) across ETP quartile distributions to evaluate the risk of enhanced TG. RESULTS: We studied 102 patients, 77.5% were female, mean age was 41.2 ± 12.1 years, and mean BMI was 45.5 ± 7.0 k/m2. Total cholesterol and fibrinogen levels were found to be independent risk factors for patients in the 4th quartile distribution of the ETP distribution (OR (95% CI)) 2.6 (1.2 to 5.4) (P = 0.01) and 2.2 (1.1 to 4.5 (P = 0.03). Patients in the 4th quartile of the ETP distribution had a lower ETP 1 month after surgery (157 (144-196) vs. 120 (98-140); P < 0.001) in parallel with a trend toward lower total cholesterol levels (5.0 ± 0.9 vs. 4.4 ± 1.0; P = 0.06). Fibrinogen levels were stable (4.5 ± 1.0 vs. 4.4 ± 0.9); P = 0.7). CONCLUSIONS: Our study highlights the role of total cholesterol and blood inflammatory marker levels in enhancing ETP in morbidly obese patients. Further studies are necessary to confirm the decreased ETP following LBS with the expected reduced inflammatory marker and total cholesterol levels.