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Rivaroxaban is a new oral direct factor Xa inhibitor recently approved for the treatment of venous thromboembolism (VTE) and for the prevention of stroke in nonvalvular atrial fibrillation (AF). Using a modified Delphi method, a group of Italian multidisciplinary specialists (internists, hematologists, angiologists, cardiologists, neurologists) guided by an expert panel reviewed the practical management of these clinical conditions in different healthcare settings and debated the limitations and gaps in clinical studies, national guidelines and the role of rivaroxaban in VTE and nonvalvular AF. This survey, named "EXTRA project", was divided into two arms (EXTRA-VTE, EXTRA-AF) and took place in two phases: the first was based on a questionnaire filled out on-line, and the second was a meeting attended by all the specialists to address the most controversial topics. Almost all of the participants expressed agreement in considering rivaroxaban a new cornerstone of stroke prevention and treatment of VTE. They appreciated its predictable pharmacokinetics and pharmacodynamics, the wide therapeutic window, the lack of relevant interactions with many commonly prescribed co-medications, no requirement for routine coagulation monitoring or dose adjustment, and the good tolerability in a broad spectrum of patients at high risk of complications. The results are here reported and discussed together with the therapeutic contextualization and the future clinical perspectives of rivaroxaban.

Venous thromboembolic disease (VTE) is a major cause of morbidity and mortality. Unfractioned heparin, low-molecular weight heparins and vitamin K antagonists, currently used in the prophylaxis and treatment of VTE, are effective and relatively safe. Otherwise, they have some important limitations (narrow therapeutic window, highly variable dose-response relationship; limitation by the need of parenteral administration for heparins and the risk of heparin-induced thrombocytopenia) which provide opportunities for new antithrombotic drugs. These drugs include: inhibitors of factors IXa and factor VIIa/tissue factor complex, agents that enhance the protein C anticoagulant pathway, direct and antithrombin-dependent Xa inhibitors, direct and indirect thrombin inhibitors. Fondaparinux and idraparinux, two new indirect parenteral factor Xa inhibitors, have been studied in well conducted trials, showing interesting results both in the prevention and in the treatment of VTE. Ximelagatran, the first orally available thrombin inhibitor, represents a promising new anticoagulant drug for the prophylaxis of VTE after major orthopedic surgery and for the treatment of deep vein thrombosis.

Sepsis and septic shock represent a frequent cause of mortality in Intensive Care Units, despite of the progress in antibiotic therapy and in the hemodynamic and respiratory support. The most frequent cause of death is the Multi Organ Dysfunction Syndrome (MODS), which is the clinical manifestation of the irreversibile damage of the microvascular bed. During sepsis and septic shock both activation of coagulation /fibrinolysis and release of mediators of inflammation contribute to the pathogenesis of disseminated intravascular coagulation (DIC); in particular the formation of fibrin in the microvascular bed is the pathological substrate of the clinical development of MODS. The rationale for employing antithrombin (AT) concentrates in the treatment of DIC associated to sepsis is based on the consideration that AT plasma levels are always decreased in patients with sepsis or septic shock; furthermore, the degree of the decrease is directly proportional to the severity of the disease and the prognosis and low AT plasma activities correlate with high mortality. AT has a double function: anticoagulant and anti-inflammatory. The most important mechanism responsible of the anti-inflammatory properties of AT is the binding to the glycosaminoglycans of the endothelial cells and the consequent release of prostacyclin. During sepsis and septic shock, treatment with AT was able, especially in animal models but also in clinical studies, to decrease plasma levels of mediators of inflammation and in some case to preserve organ failure and to reduce mortality.

Background: The aim of our study was to evaluate spontaneous conversion rate to sinus rhythm in patients with paroxysmal atrial fibrillation (AF) not submitted to any treatment (pharmacological and/or electrical)., Methods: From January 1985 to September 1990, 123 consecutive patients with paroxysmal AF were hospitalized in our department. In 11 patients arrhythmia was due to arrhythmogenic conditions; 34 patients were submitted to emergency treatment with drugs (23 cases) or electrical cardioversion (11 cases); 78 patients (41 males; mean age 65.1 years; 37 females: mean age 68.6 years), without emergency problems were enrolled in our study and were submitted to a four-day observation period without any therapy, except in case of worsening. 35 patients were free from heart disease; in the other 43, 28 had chronic coronary disease, 11 hypertensive cardiovascular disease, 2 rheumatic valvular disease, 1 hypertrophic cardiomyopathy and 1 chronic cor pulmonale., Results: In all 78 patients sinus rhythm was restored spontaneously - in about 90% of them within 24 hours. Mean time to conversion was 21 hours (range 1-96 hours). Cardioversion occurred in similar percentage and at the same time in both subgroups of patients (with and without heart disease)., Conclusions: Therefore, given the risks and cost of every treatment, a 24-hour observation period without therapy could be useful in those patients presenting with paroxysmal atrial fibrillation without emergency problems.