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To realize a machine learning (ML) model to estimate the dose of low molecular weight heparin to be administered, preventing thromboembolism events in COVID-19 patients with active cancer. Methods: We used a dataset comprising 131 patients with active cancer and COVID-19. We considered five ML models: logistic regression, decision tree, random forest, support vector machine and Gaussian naive Bayes. We decided to implement the logistic regression model for our study. A model with 19 variables was analyzed. Data were randomly split into training (70%) and testing (30%) sets. Model performance was assessed by confusion matrix metrics on the testing data for each model as positive predictive value, sensitivity and F1-score. Results: We showed that the five selected models outperformed classical statistical methods of predictive validity and logistic regression was the most effective, being able to classify with an accuracy of 81%. The most relevant result was finding a patient-proof where python function was able to obtain the exact dose of low weight molecular heparin to be administered and thereby to prevent the occurrence of VTE. Conclusions: The world of machine learning and artificial intelligence is constantly developing. The identification of a specific LMWH dose for preventing VTE in very high-risk populations, such as the COVID-19 and active cancer population, might improve with the use of new training ML-based algorithms. Larger studies are needed to confirm our exploratory results.

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Vitamin K antagonists have been used for many years as the treatment of choice for long-term oral anticoagulation in patients with non-valvular atrial fibrillation. Unfortunately, the use of those drugs in the real-world setting, particularly among elderly patients, is suboptimal because of their limitations in management. Therefore, many patients were not adequately anticoagulated. Direct oral anticoagulants have been demonstrated to overcome almost all the limitations derived from the use of vitamin K antagonists. Direct oral anticoagulants are at least as effective as vitamin K antagonists in preventing thromboembolic events in patients with non-valvular atrial fibrillation and safer in reducing the risk of intracranial haemorrhage and all-cause mortality. However, as a result of the strict inclusion and exclusion criteria applied to patients, data coming from randomized controlled trials might not apply to the general population. Furthermore, elderly patients were scarcely represented in randomized controlled trials with direct oral anticoagulants. Therefore in elderly patients with non-valvular atrial fibrillation, unmet clinical needs still exist. This review article highlights some of them and provides potential answers based on the results coming from randomized clinical trials, real-world data, and the authors’ clinical experience.

Background: The optimal management of patients with isolated distal deep vein thrombosis (IDDVT) is uncertain. Observational studies report similar therapeutic strategies as for patients with proximal DVT or pulmonary embolism (PE), but shorter treatment duration. We compared two different durations of treatment with rivaroxaban in patients with symptomatic IDDVT. Methods: In a randomized, double-blind, placebo-controlled trial, patients with symptomatic IDDVT received 6 weeks of rivaroxaban at standard doses and were assigned to rivaroxaban 20 mg once daily or placebo for additional 6 weeks. Randomization was done using a computer-generated randomization list and was stratified by study center. Primary efficacy outcome was a composite of recurrent IDDVT, proximal DVT, symptomatic or fatal PE. Primary safety outcome was ISTH-defined major bleeding. We here report the results of the 6-month follow-up. Findings: Of the 402 randomized patients, 200 received rivaroxaban and 202 placebo. IDDVT was unprovoked in 41.0% and 42.6% of patients, respectively. The primary efficacy outcome occurred in 5 patients (2.5%) on rivaroxaban and 21 (10.4%) treated with placebo (p=0.001). Recurrent IDDVT occurred in 3 (1.5%) and 16 (7.9%)(p=0.002); proximal DVT or PE in 2 (1.0%) and 5 (2.5%) (p=0.45), respectively. There were 3 (0.7%) major bleeding events prior to randomization, none after randomization. Interpretation: Rivaroxaban administered for 3 months effectively and safely reduces recurrent venous thrombosis as compared to 6 weeks of treatment during a 6-month follow up. The incidence of proximal DVT and PE was low and similar between the two groups. Clinical Trial Registration Details: EudraCT Number: 2016-000958-36. Clinical Trial Gov identifier: NCT02722447. Funding Information: Unrestricted grant from Bayer Italy. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the local institutional review boards or ethics committees of all participating centers and was performed in accordance with the declaration of Helsinki (52nd WMA General Assembly, Edinburgh, Scotland, October 2000) as well as with the International Conference on Harmonisation (ICH) guidelines on Good Clinical Practise (GCP).

Background. According to recent guidelines, all hospitalized patients with COVID-19 should receive pharmacological prophylaxis for venous thromboembolism (VTE), unless there are specific contraindications. However, the optimal preventive strategy in terms of intensity of anticoagulation for these patients is not well established. Objectives. To investigate the impact of individualized regimens of enoxaparin on the development of VTE and on the risk of major bleeding complications during hospitalization in patients with COVID-19 infection. Methods. All consecutive patients admitted to the medical wards of six Italian hospitals between 15 September and 15 October 2020 with COVID-19 infection of moderate severity were administered enoxaparin in subcutaneous daily doses adjusted to the Padua Prediction Score stratification model: No heparin in patients scoring less than 4, 4000 IU daily in those scoring 4, 6000 IU in those scoring 5, and 8000 in those scoring six or more. Objective tests were performed in patients developing clinical symptoms of deep vein thrombosis and/or pulmonary embolism. Bleeding complications were defined according to the ISTH classification. Results. From the 154 eligible patients, enoxaparin was administered in all: 4000 IU in 73 patients, 6000 IU in 53, and 8000 IU in the remaining 28. During the course of hospitalization, 27 patients (17.5%) died. VTE developed in 14 of the 154 patients (9.1%; 95% CI, 4.6% to 13.6%), and was fatal in 1. Major bleeding complications developed in 35 patients (22.7%; 95% CI, 16.1% to 29.3%), and were fatal in 8. Conclusions. Despite the use of risk-adjusted doses of enoxaparin, the rate of VTE events was consistent with that reported in contemporary studies where fixed-dose low-molecular-weight heparin was used. The unexpectedly high risk of bleeding complications should induce caution in administering enoxaparin in doses higher than the conventional low ones.

SARS-CoV-2 induced a pandemic that is reported to have started in Asia and was then extended to other countries in the world. Main clinical aspects of this viral infection have been lung injuries with severe pneumonia requiring prolonged hospitalization and associated morbidities such as venous thromboembolism and/or superinfection by bacteria, fungus or other pests. Immediately there was a need to develop a sustainable therapeutic strategy, such as vaccination. Vaccines against Covid-19, in fact, exert a protective action for common people and reduce viral diffusion. Yet, vaccination of a large number of people raises the question of a well-known complication of several types of vaccines; this complication is immune thrombocytopenia, which is sometimes associated with thrombosis as well. In this short review, we summarized mechanisms involved in the pathogenesis of vaccine-induced prothrombotic immune thrombocytopenia and vaccine-induced thrombocytopenic thrombosis.

Background In this prospective cohort study, we aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus heparin/vitamin K antagonists for the treatment of venous thromboembolism (VTE) in patients with inherited thrombophilia. Methods and Results We enrolled consecutive patients with acute VTE and inherited thrombophilia treated with DOACs (cases) or heparin/vitamin K antagonists (controls), matched for age, sex, ethnicity, and thrombophilia type. End points were VTE recurrence and bleeding complications; residual vein thrombosis and post‐thrombotic syndrome; VTE recurrence after anticoagulant discontinuation. Two hundred fifty‐five cases (age 52.4±17.3 years, Female 44.3%, severe thrombophilia 33.1%) and 322 controls (age 49.7±18.1 years, Female 50.3%, severe thrombophilia 35.1%) were included. The cumulative incidence of VTE recurrence during anticoagulation was 1.09% in cases versus 1.83%, adjusted hazard ratio (HR) 0.67 (95% CI, 0.16–2.77). The cumulative incidence of bleeding was 10.2% in cases versus 4.97%, HR 2.24 (95% CI 1.10–4.58). No major bleedings occurred in cases (versus 3 in controls). No significant differences regarding residual vein thrombosis and post‐thrombotic syndrome. After anticoagulant discontinuation, DOACs yielded a significantly lower 2‐year VTE recurrence risk versus traditional anticoagulants (HR, 0.61 [95% CI, 0.47–0.82]). Conclusions DOACs and heparin/vitamin K antagonists showed a similar efficacy in treating VTE in patients with thrombophilia. Although major bleeding episodes were recorded solely with heparin/vitamin K antagonists, we noted an overall increased bleeding rate with DOACs. The use of DOACs was associated with a lower 2‐year risk of VTE recurrence after anticoagulant discontinuation.

Despite the availability of updated guidelines for the diagnosis and treatment of venous thromboembolism (VTE), the management of this disorder in clinical practice is often not standardized, given the different degree of compliance with official recommendations by the various involved specialists. The aim of this consensus paper, as a result of a board of experts in thromboembolism, is to define strategies to improve the quality of patients' care and the efficiency of healthcare resources utilization, by means of: (a) analysis of the guidelines for diagnosis and treatment of VTE; (b) analysis of diagnostic and therapeutic algorithms currently used in clinical practice by different specialists; (c) agreement on a common algorithm for diagnosis and treatment of VTE in different clinical settings; (d) definition of the possible role of the new oral anticoagulant agents (NOAC), such as rivaroxaban, based on their potential benefits for both acute and chronic therapy. The so-called "single drug approach" (as opposed to the traditional heparin/VKA combination), which can be adopted with these drugs, makes anticoagulation more convenient for both patients and healthcare providers, without the need for a close monitoring of the hemocoagulative status, and with a concomitant reduction of length of hospitalization and treatment costs. Among NOACs, in this paper we focused on rivaroxaban only because it was the unique available NOAC in Italy for the treatment of VTE at the time the manuscript was written. Concerning rivaroxaban, the results of two phase III, randomized and controlled trials confirm the non-inferiority of this drug compared to standard therapy (enoxaparin/warfarin) for the treatment of patients with pulmonary embolism (EINSTEIN PE Study) or deep vein thrombosis (EINSTEIN DVT Study) in terms of both efficacy and safety, supporting its use as an effective therapeutic option for these disorders.

The association between venous and arterial thrombotic disorders is still unclear. We assessed the association between residual vein thrombosis (RVT) and subclinical atherosclerosis in a cohort of patients with unprovoked (or associated with weak risk factors) proximal deep-vein thrombosis (DVT).In a multicenter cross-sectional study, consecutive patients over 40years free from atherosclerotic disorders received the ultrasound assessment of the leg vein system and that of carotid arteries approximately three months after an episode of proximal DVT. In each center the evaluation was done by two independent assessors. The presence of RVT was defined as the incompressibility of at least 4mm in either the popliteal or the common femoral vein, and that of subclinical atherosclerosis as the presence of increased (0.9mm) intima-media tickness (IMT) and/or carotid plaques.Out of 252 patients (mean age, 67; males, 53%; unprovoked, 77%), the presence of RVT was found in 139 (55.2%). An increased IMT was shown in 76 (54.7%) patients with and in 35 (31.0%) without RVT (p0.001). At least one carotid plaque was found in 80 (57.6%) patients with and in 36 (31.9%) without RVT (p0.001). After adjusting for the baseline characteristics, the odds ratio of subclinical atherosclerosis (increased IMT and/or carotid plaques) was 2.8 (95% CI, 1.6 to 4.7).The ultrasound detection of RVT after an episode of proximal DVT that is either unprovoked or triggered by weak risk factors is associated with a higher prevalence of subclinical atherosclerosis. These findings may have implications for patient prognosis.

Background The recanalization rate in patients with deep venous thrombosis (DVT) of the legs treated with the direct oral anticoagulants (DOAC) is unknown. Methods In an Italian cohort, we investigated the rate of residual vein thrombosis (RVT) after three and/or six months in 352 patients with proximal DVT who had been treated with the DOACs as a stand-alone therapy or lead-in parenteral anticoagulants, and compared it to that recorded in a historical cohort of 1094 patients in which vitamin K antagonists (VKAs) had been employed. In both cohorts, RVT was defined as the ultrasound persistence of thrombotic material resulting in a diameter of at least 4 mm of incompressibility of the proximal veins. Results RVT was detected in 143 patients treated with DOACs (41.2%) after three months and in 58 patients (21.1%) after six months; the corresponding figure in patients treated with conventional anticoagulation was 52.3% and 54.5%, respectively. After adjusting for the baseline characteristics, the odds ratio of RVT in patients treated with the DOACs as compared with those treated with conventional anticoagulation was 0.63 (95% CI, 0.48–0.81) after three months, and 0.17 (95% CI; 0.11–0.26) after six months. Conclusions In patients with proximal DVT treated with the DOACs, the persistence of ultrasound detectable RVT is likely to occur less frequently than in patients treated with conventional anticoagulation. These results may have implications for the prognosis of patients with DVT.

Real-life studies complement data from registrative trials. Because of the delayed registration of direct oral anticoagulants in Italy, scarce real-life data on such treatments is available for the Italian population. The aim of the MAC project is to collect real-life clinical information in unselected patients given oral anticoagulants for venous thromboembolism, during a 5-year follow-up period. This is a prospective-cohort, multi-center, observational study performed in four Italian centers. The estimated samples size is 4,000 patients. The efficacy outcomes are: incidence of symptomatic recurrent venous thromboembolism and of post-thrombotic syndrome. The safety outcomes are: incidence of major bleeding, clinically relevant non-major bleeding, minor bleeding, serious adverse events, and mortality. The MAC project has the potential to improve our understanding of the epidemiology and of the therapeutic strategies adopted in Italian patients with venous thromboembolism.Clinical Trial Registration: WWW.ClinicalTrials.Gov, identifier: NCT0432939.

Background The clinical benefit of extending prophylaxis for venous thromboembolism (VTE) beyond hospital discharge after laparoscopic surgery for cancer is undefined. Extended prophylaxis with rivaroxaban is effective in reducing post-operative VTE after major orthopedic surgery without safety concern. Methods PROLAPS II is an investigator-initiated, randomized, double-blind study aimed at assessing the efficacy and safety of extended antithrombotic prophylaxis with rivaroxaban compared with placebo after laparoscopic surgery for colorectal cancer in patients who had received antithrombotic prophylaxis with low molecular-weight heparin for 7 ± 2 days (NCT03055026). Patients are randomized to receive rivaroxaban (10 mg once daily) or placebo for 3 weeks (up to day 28 ± 2 from surgery). The primary study outcome is a composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT or VTE-related death at 28 ± 2 days from laparoscopic surgery. The primary safety outcome is major bleeding defined according to the International Society of Thrombosis and Haemostasis. Symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected DVT, major bleeding or death by day 28 ± 2 and by day 90 from surgery are secondary outcomes. Assuming an 8% event rate with placebo and 60% reduction in the primary study outcome with rivaroxaban, 323 patients per group are necessary to show a statistically significant difference between the study groups. Discussion The PROLAPS II is the first study with an oral anti-Xa agent in cancer surgery. The study has the potential to improve clinical practice by answering the question on the clinical benefit of extending prophylaxis after laparoscopic surgery for colorectal cancer.

Despite thromboprophylaxis, patients with coronavirus‐19 disease (COVID‐19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of the study was to evaluate the incidence of venous thromboembolism in COVID‐19 patients admitted to both intensive care unit and medical ward. Consecutive patients admitted for COVID‐19 to medical ward and intensive care unit at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of internal jugular, upper and lower limbs veins every 7(±1) days after the admission; and if negative, once‐weekly until discharge or death. In case of suspected pulmonary embolism, a multi‐detector computed tomographic angiography was performed. The primary outcome was the proportion of any deep‐vein thrombosis and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020 a total of 85 patients were investigated, 44 (52%) in medical ward and 41 (48%) in intensive care unit. Despite thromboprophylaxis, venous thromboembolism occurred in 12 medical ward (27.3%) and 31 intensive care unit patients (75.6%) with an Odds Ratio of 9.3 (95%CI, 3.5 to 24.5;p

Background: Despite thromboprophylaxis, patients with COVID-19 exhibit intense coagulation activation and higher risk of venous thromboembolism (VTE), even though the real VTE incidence is still unknown. We evaluated the incidence of objectively documented VTE in COVID-19 patients admitted to both intensive care unit (ICU) and medical ward (MW). Methods: Consecutive patients admitted for COVID-19 to MW and ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of internal jugular, upper and lower limbs veins every 7(±1) days after the admission; and if negative, once-weekly until discharge or death. In case of suspected pulmonary embolism, a multi-detector computed tomographic angiography was performed. The primary outcome was the proportion of any deep-vein thrombosis and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. Findings: From March 4 to April 30, 2020 a total of 85 patients were investigated, 44 (52%) in MW and 41 (48%) in ICU. Despite thromboprophylaxis, VTE occurred in 12 MW (27·3%) and 31 ICU patients (75·6%) with an OR of 9·3 (95%CI, 3·5 to 24·5, p

COVID-19 is an infection due to SARS-CoV-2; this virus has been identified as the cause of the present pandemic. Several typical characteristics are present in this infection, in particular pneumonia with possible lung failure, but atypical clinical presentations are being described daily by physicians around the world. Ground-glass opacities with pneumonia are the most common and dangerous presentations of the COVID-19 disease, and they are usually associated with positive nasopharyngeal swab (NPS) tests with detectable SARS-CoV-2 viral RNA. Compared to the general population, hospital workers have been at a greater risk of infection ever since the first patients were hospitalized. However, hospital workers have also been reported as having COVID-like symptoms despite repeated negative swab tests but having tested positive for SARS-CoV-2 antibodies with serological tests. We can postulate that a COVID-like syndrome is possible, in particular in hospital workers, that is characterized by symptoms similar to those of COVID-19, but with repeated negative nasopharyngeal swabs. These repeated negative NSPs make the difference in daily clinical management with people that experienced a single false negative nasopharyngeal swab; furthermore, a clear clinical differentiation of these situations is still lacking in the literature. For this reason, here, we report our main findings from a cohort of patients with a COVID-like syndrome compared to a similar group affected by typical COVID-19.

Essentials The Constans score and D-dimer can rule out upper extremity deep vein thrombosis without imaging. We evaluated the performance of an extended Constans score and an age-adjusted D-dimer threshold. The extended Constans score did not increase the efficiency compared to the original score. Age-adjusted D-dimer testing safely increased the efficiency by 4%, but this needs validation. SummaryBackground Among patients with clinically suspected upper extremity deep vein thrombosis (UEDVT), a clinical decision rule based on the Constans score combined with D-dimer testing can safely rule out the diagnosis without imaging in approximately one-fifth of patients. Objectives To evaluate the performance of the original Constans score, an extended Constans score and an age-adjusted D-dimer positivity threshold. Methods Data of 406 patients with suspected UEDVT previously enrolled in a multinational diagnostic management study were used. The discriminatory performance, calibration and diagnostic accuracy of the Constans score were evaluated. The Constans score was extended by selecting clinical variables that may have incremental value in detecting UEDVT, conditional on the original Constans score items. The performance of the Constans rule was evaluated in combination with fixed and age-adjusted D-dimer thresholds. Results The original Constans score showed good discriminatory performance (c-statistic, 0.81; 95% confidence interval [CI], 0.76–0.85). An extended Constans score with five additional clinical items improved discriminatory performance and calibration, but this did not translate into a higher efficiency in avoiding imaging tests. Compared with a fixed threshold, age-adjusted D-dimer testing increased the proportion of patients for whom imaging and anticoagulation could be withheld from 21% to 25% (gain, 3.7%; 95% CI, 2.3–6.0%). Conclusions The Constans score has good discriminatory performance in the diagnosis of UEDVT. Age-adjusted D-dimer testing is likely to safely increase the efficiency of the diagnostic algorithm, but this approach needs prospective validation.

Essentials Few data exist on outcome of upper extremity deep and superficial vein thrombosis (UEDVT and UESVT). We followed 102 and 55 patients with UEDVT or UESVT, respectively, for a median of 3.5 years. Risk of recurrent venous thromboembolism was low in both diseases, and the mortality high. Postthrombotic symptoms were infrequent and cancer patients had a higher risk of recurrent VTE. Background There is scant information on the optimal management and clinical outcome of deep and superficial vein thrombosis of the upper extremity (UEDVT and UESVT). Objectives To explore treatment strategies and the incidence of recurrent venous thromboembolism (VTE), mortality, postthrombotic symptoms, and bleeding in patients with UEDVT and UESVT and to assess the prognosis of cancer patients with UEDVT. Patients/methods Follow-up of patients with UEDVT or UESVT, who were enrolled previously in a diagnostic management study. Results We followed 102 and 55 patients with UEDVT and UESVT, respectively, both for a median of 3.5 years. Anticoagulant treatment was started in 100 patients with UEDVT (98%) and in 40 (73%) with UESVT. Nine patients with UEDVT (9%) developed recurrent VTE, 26 (26%) died, 6 (8%) of 72 patients had moderate postthrombotic symptoms, and 5 (5%) experienced major bleeding. One patient with UESVT had a recurrent VTE, 18 (33%) died, none had moderate postthrombotic symptoms, and none had major bleeding. Of the cancer patients with UEDVT, 18% had recurrent VTE vs. 7.5% in non-cancer patients (adjusted hazard ratio 2.2, 95%CI 0.6-8.2). The survival rate was 50% in cancer patients with UEDVT vs. 60% in those without (adjusted HR 0.8, 95%CI 0.4-1.4). Conclusions The risk of recurrent VTE was low in patients with UEDVT, and negligible for UESVT. Mortality was high for both diseases. Postthrombotic symptoms were infrequent and mild. Anticoagulant therapy of UEDVT carried a substantial risk of major bleeding. Cancer patients had a significant risk of recurrent VTE

Chronic venous disease (CVD) is a common condition with major health consequences that is associated with poor long-term prognosis, significant socioeconomic impact, disabling symptoms and reduced quality of life. To provide practical guidance for diagnosis and management of CVD, a Delphi panel of 5 experts in steering committee and 28 angiologists/vascular surgeons met with the major aim of providing a supplement for established national and international guidelines. A total of 24 statements were voted upon in two rounds, of which consensus was reached on 22 statements, indicating a high level of overall agreement. Consensus was reached on 7 of 8 statements relative to diagnosis (CEAP classification, diagnostic tools, QoL assessment, diagnostic imaging) and on 15 of 16 statements on management (conservative treatments, compressive therapy, pharmacological therapy, surgical treatment). The results of the consensus reached are discussed herein from which it is clear that diagnostic and management approaches utilising personalised therapies tailored to the individual patient should be favoured. While it is clear that additional studies are needed on many aspects of diagnosis and management of CVD, the present Delphi survey provides some key recommendations for clinicians treating CVD that may be useful in daily practice.

Introduction In a management study, a diagnostic algorithm consisting of a clinical decision rule, D-dimer, and ultrasonography was shown to safely exclude upper extremity deep vein thrombosis (UEDVT). Efficiency may be lower in high-risk subgroups: those with a central venous catheter or pacemaker, inpatients, cancer, and elderly patients. Methods Data of 406 patients with suspected UEDVT enrolled in a prospective management study were used for the present analysis. The aim was to evaluate the efficiency of the algorithm in subgroups, defined as the proportion of patients in whom imaging could be safely withheld based on the combination of a decision rule result indicating “UEDVT unlikely” and a normal D-dimer result. Results The strategy excluded UEDVT in 87 of 406 patients (21%); ultrasonography was withheld in these patients and none developed UEDVT during 3 months of follow-up. In contrast, ultrasonography could be withheld in only 4 of 92 patients with a catheter or pacemaker (4.3%; 95% CI: 1.7% to 11%) and in 4 of 83 inpatients (4.8%; 95% CI: 1.9% to 12%). The efficiency was 11% in patients with cancer and 13% in those older than 75 years. Conclusion Although the combination of a decision rule and D-dimer testing is safe in excluding UEDVT in the overall population of patients with suspected UEDVT, its efficiency appears limited in some subgroups, in particular those with a central venous catheter or pacemaker, and inpatients.

Background The optimal long-term strategy for preventing recurrent venous thromboembolism (VTE) in patients with deep-vein thrombosis (DVT) is uncertain. Methods In 620 consecutive outpatients with a first proximal DVT who had completed at least three months of anticoagulation (unprovoked in 483, associated with minor risk factors in 137), the ultrasound presence of residual vein thrombosis (RVT) was assessed and defined as an incompressibility of at least 4 mm. In 517 patients without RVT and with negative D-dimer, anticoagulation was stopped and D-dimer was repeated after one and three months. Anticoagulation was resumed in 63 of the 72 patients in whom D-dimer reverted to positivity. Results During a mean follow-up of three years, recurrent VTE developed in 40 (7.7%) of the 517 patients, leading to an annual rate of 3.6% (95% CI, 2.6 to 4.9): 4.1% (95% CI, 2.9 to 5.7) in individuals with unprovoked DVT, and 2.2% (95% CI, 1.1 to 4.5) in those with DVT associated with minor risk factors. Of the 233 males with unprovoked DVT, 17 (7.3%) developed events in the first year of follow-up. Major bleeding complications occurred in 8 patients while on anticoagulation, leading to an annual rate of 1.2% (95% CI, 0.6 to 2.4). Conclusions Discontinuing anticoagulation in patients with a first episode of proximal DVT based on the assessment of RVT and serial D-dimer leads to an overall annual rate of recurrent VTE lower than 5.0%, which is the rate deemed as acceptable by the Subcommittee on Control of Anticoagulation of the ISTH. However, in males with unprovoked DVT there is room for further improving the long-term strategy of VTE prevention. ( ClinicalTrials.gov number, NCT01285661 ).

Background and aims Whether carotid atherosclerosis is associated with an increased risk for ischemic stroke in patients with atrial fibrillation (AF) on anticoagulant treatment is undefined. To explore this association, patients with AF on treatment with vitamin K antagonists were included in a multicenter, prospective study. Methods At inclusion in the study, patients underwent Doppler-ultrasonography for the assessment of carotid atherosclerosis and then were prospectively followed. Ischemic stroke or transient ischemic attack (TIA) were the primary study outcomes; death and its causes were reported. Results Overall, 587 patients were included in the study. At ultrasonography, 380 patients had carotid atherosclerosis (64.7%) and 45 internal carotid (ICA) stenosis ≥50% (7.7%). During a mean follow-up of 41 ± 15 months, 30 patients had an ischemic stroke or TIA (1.49% per patient-year, 95% CI 0.96–2.03) and 81 patients died (4.01% per patient-year, 95% CI 3.16–4.86). Carotid atherosclerosis was associated with a significant increase in the risk for the composite of ischemic stroke or TIA or death after adjusting for CHA2DS2VASc (6.0% vs. 3.1% patient-year; HR 1.60, 95% CI 0.99–2.59; p = 0.05). ICA ≥50% was associated with a not significant increase in the risk of ischemic stroke or TIA (2.05% vs. 1.45% patient-year; HR 1.39, 95% CI 0.42–4.58) or all-cause death (6.1% vs. 3.8% patient-year; HR 1.66, 95% CI 0.83–3.32). Conclusions In patients with AF, carotid atherosclerosis is a predictor for the composite of cerebrovascular events or death while on anticoagulant therapy. In patients with AF and carotid atherosclerosis, the clinical benefit of a more intense antithrombotic treatment should be evaluated.

Distal deep venous thrombosis (DDVTs) is one of the “grey” areas of venous thromboembolism. There is a great heterogeneity in the diagnostic and therapeutic strategies between all the diagnostic centers. Studies doesn’t clarify the problem so it is not clear yet if there is any advantage in diagnosing and consequentially treating all the IDDVT. The 2012 ACCP guidelines suggested clinical observation for 2 weeks over initial anticoagulation (grade 2C) in patients with acute IDDVT without severe symptoms or risk factors for extension.

Background: Chronic venous disease (CVD) is a common clinical condition, especially relevant for its impact on public health and its related economic burden. Veno-Active Drugs (VAD) are an heterogeneous group of drugs, widely used in the treatment of CVD. In the last years some food supplements, similar to VAD but with different compounds concentrations raised some confusion in this field. The complex Lypoic acid, Ginkgoselect phytosome and Leucoselect phytosome is a food supplement based on molecules exhibiting different but synergic activities never prospectively tested in patients with CVD. Methods: Consecutive ambulatory patients with objectively documented CVD and a CEAP “C” up to 5 were eligible for the study. Patients were to take 1 fast-slow tablet of the complex twice-daily for 2 months, followed by 1 fast-slow tablet once-daily for other 4 months, for a total of 6 months. Presence and magnitude of CVD-related signs and symptoms (with “C” of the CEAP classification), evaluation of patients’ quality of life (with VEINES-QoL/Sym questionnaire) and assessment of safety and tolerability of the complex at baseline and after 2 and 6 months (with revised Venous Clinical Severity Score, rVCSS) were recorded. Results: 97 patients enrolled and evaluated. The proportion (65%) of the patients with a rVCSS score>5 at baseline decreased to 35% at 6 months (P