Direct oral anticoagulants for the treatment of splanchnic vein thrombosis: A state of art

Splanchnic vein thrombosis (SVT) is a manifestation of venous thromboembolism in an unusual site. Portal, mesenteric, and splenic veins are the most common vessels involved in SVT which occurs mainly in patients with liver cirrhosis, although non-cirrhotic patients could be affected as well. Thrombosis of hepatic veins, also known as Budd-Chiari syndrome, is another manifestation of SVT. Prompt diagnosis and intervention are mandatory in order to increase the recalization rate and reduce the risk of thrombus progression and hypertensive complications. Traditional anticoagulation with heparin and vitamin-K antagonists is the treatment of choice in these cases. However, recent studies have shown promising results on the efficacy and safety of direct oral anticoagulants (DOACs) in this setting. Available results are mainly based on retrospective studies with small sample size, but first clinical trials have been published in the last years. This manuscript aims to provide an updated overview of the current evidence regarding the role of DOACs for SVT in both cirrhotic and non-cirrhotic patients

Thrombocytopenia and Mortality Risk in Patients With Atrial Fibrillation: An Analysis From the START Registry

Background: Thrombocytopenia is associated with increased mortality in the general population, but few data exist in patients with atrial fibrillation (AF) taking oral anticoagulants. We investigated factor determinants of thrombocytopenia in a large cohort of patients affected by AF and its association with total mortality. Methods and Results: Multicenter prospective cohort study, including 5215 patients with AF from the START (Survey on Anticoagulated Patients Register) registry, 3877 (74.3%) and 1338 (25.7%) on vitamin K or non\u2013vitamin K antagonist oral anticoagulants, respectively. Thrombocytopenia was defined by a platelet count <150 7109/L. Determinants of thrombocytopenia were investigated, and all-cause mortality was the primary survival end point of the study. Thrombocytopenia was present in 592 patients (11.4%). At multivariable logistic regression analysis, chronic kidney disease (odds ratio [OR], 1.257; P=0.030), active cancer (OR, 2.065; P=0.001), liver cirrhosis (OR, 7.635; P<0.001), and the use of diuretics (OR, 1.234; P=0.046) were positively associated with thrombocytopenia, whereas female sex (OR, 0.387; P<0.001) and the use of calcium channel blockers (OR, 0.787; P=0.032) were negatively associated. During a median follow-up of 19.2 months (9942 patient-years), 391 deaths occurred (rate, 3.93%/year). Mortality rate increased from 3.8%/year to 9.9%/year in patients with normal platelet count and in those with moderate-severe thrombocytopenia, respectively (log-rank test, P=0.009). The association between moderate-severe thrombocytopenia and mortality persisted after adjustment for CHA2DS2 VASc score (hazard ratio, 2.431; 95% CI, 1.254\u20134.713; P=0.009), but not in the fully adjusted multivariable Cox regression analysis model. Conclusions: Thrombocytopenia is common in patients with AF. Despite an increased incidence of mortality, thrombocytopenia was not associated with mortality at multivariable analysis. Thrombocytopenia may reflect the presence of comorbidities associated with poor survival in AF

Comparison of anticoagulation quality between acenocoumarol and warfarin in patients with mechanical prosthetic heart valves: Insights from the nationwide PLECTRUM study

Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

LA PREVENZIONE DELLE LEGIONELLOSI NEI TURISTI

ObiettiviIl problema della legionellosi nei viaggiatori è di particolare interesse per la presenza di numerose strutture turistiche contaminate da Legionella. L’Italia risulta essere il secondo paese europeo per numero di casi nei viaggiatori, con una inevitabile ricaduta negativa sul turismo, tanto che nel 2005 sono state emanate dall’ISS linee guida intese a favorire l’adozione di sistemi di prevenzione da parte dei gestori di strutture turistico-recettive e termali. L’indagine qui riportata si riferisce alla comparsa di numerosi casi nella riviera romagnola ed ai successivi interventi mirati a contenere il fenomeno. Materiali e metodi. Nell’estate del 2003, sono pervenute al Dipartimento di Sanità Pubblica 10 notifiche di Malattia dei Legionari in persone che avevano soggiornato in alberghi della zona. Il Dipartimento ha immediatamente attuato un sistema di sorveglianza sulle strutture interessate, verificando la contaminazione del sistema idrico e l’adozione di opportune misure di bonifica ambientale. Al fine di prevenire la ricomparsa di casi, sono state attuati incontri di informazione/formazione con i gestori ed è stata resa obbligatoria, tramite ordinanza del Sindaco, la istituzione del registro della manutenzione idro-potabile per tutte le strutture alberghiere. Negli anni successivi è stato attuato un monitoraggio per verificare, a campione e sulle strutture interessate dai casi, se gli alberghi avevano adottato i protocolli di manutenzione e se risultavano ancora contaminati da Legionella. Risultati. Si è assistito nel tempo ad una progressivo adeguamento degli alberghi alle misure di prevenzione, con una radicale riduzione del numero di casi ed un progressivo aumento di strutture esenti da contaminazione.Discussione. Il nostro studio documenta che le misure per il controllo della legionellosi sono efficaci soprattutto se accompagnate da una attenta sorveglianza da parte degli igienisti del territorio, il cui ruolo nella informazione, gestione e controllo del rischio appare indispensabile sia nel momento della comparsa di casi che nel lungo periodo

D-dimer and reduced dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study.

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study we aimed at assessing the value of an algorithm incorporating serial D-dimer testing and administration of reduced dose apixaban (2.5 mg twice daily) only to patients with positive test. 732 outpatients aged 18 to 74 years, anticoagulated for at least 12 months after a first unprovoked VTE were included. Patients underwent D-dimer testing with commercial assays and pre-established cutoffs. If the baseline D-dimer, during anticoagulation, was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286; 39.1%) were left without anticoagulation. At first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% CI, 4.5 to 11.2), including symptomatic proximal DVT or PE recurrence, death for VTE, major bleeding, occurring in patients off anticoagulation, versus that in those receiving apixaban (1.1%; 95% CI, 0.4 to 2.6; adjusted HR, 8.2; 95% CI, 3.2 to 25.3). In conclusion, in patients anticoagulated for at least one year after a first unprovoked VTE, the decision whether to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced dose apixaban against recurrences. ClinTrials.gov: NCT03678506

Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: Randomised controlled trial

Objective: To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT). Design: Randomised, double blind, placebo controlled clinical trial. Setting: 28 outpatient clinics specialising in venous thromboembolism. Participants: 402 adults (≥18 years) with symptomatic isolated distal DVT. Interventions: After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion. Main outcomes measures: The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes. Results: 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred. Conclusions: Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage. Trial registration: EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447

The negative predictive value of D-dimer on the risk of recurrent venous thromboembolism in patients with multiple previous events: A prospective cohort study (the PROLONG PLUS study).

none12noneAgeno W;Cosmi B;Ghirarduzzi A;Santoro R;Bucherini E;Poli D;Prisco D;Alatri A;Pengo V;Galli L;Dentali F;Palareti GAgeno, W; Cosmi, B; Ghirarduzzi, A; Santoro, R; Bucherini, E; Poli, D; Prisco, D; Alatri, A; Pengo, Vittorio; Galli, L; Dentali, F; Palareti, G