The left atrial appendage: from embryology to prevention of thromboembolism.

The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches.

Managing dentoalveolar surgical procedures in patients taking new oral anticoagulants.

The development of new orally administered anticoagulants, such as dabigatran, rivaroxaban, and apixaban, in the past few years has focused on avoiding some of the drawbacks associated with warfarin. This work aims to illustrate the main features of the most commonly used new oral anticoagulants, reviewing the current literature on the management of patients taking these drugs and needing oral and implant surgery, and discussing the currently proposed related guidelines.

The benefit of betrixaban for the extended thromboprophylaxis in acutely ill medical patients.

INTRODUCTION: Patients admitted with acute medical conditions are at prolonged risk for venous thrombosis. The efficacy and safety, and the appropriate duration of thromboprophylaxis have not been clearly determined. In recent years, direct coagulation factor inhibitors have been successfully tested for the prevention and treatment of arterial and venous thromboembolism. Betrixaban is a novel direct inhibitor of factor Xa with a noteworthy pharmacological feature: limited renal clearance. Areas covered: This review focuses on the pharmacological profile of Betrixaban, including its clinical efficacy and safety. It also covers the results of the pivotal APEX trial assessing the safety and efficacy of betrixaban for extended thromboprophylaxis in patients with acute medical conditions. Expert opinion: The role of extended thromboprophylaxis in acutely ill medical patients is subject to debate. The beneficial results in terms of VTE prevention were offset by the relevant increase in major bleeding. Betrixaban is the only direct oral anticoagulant to have shown a favorable risk-benefit profile in this setting especially in patients at higher risk for thrombosis.

Data from a multidisciplinary poll of 178 expert physicians on the usage of non-vitamin K Oral Anticoagulants in patients with atrial fibrillation and venous thromboembolism.

This data article contains data from a multidisciplinary questionnaires filled in by 178 expert physicians on the usage of non-vitamin K Oral Anticoagulants in patients with atrial fibrillation (AF) and for the treatment of patients with venous thromboembolism (VTE). The questionnaire consists of 9 statements of clinical complex AF and VTE cases and informative campaign on antithrombotic therapy for stroke prevention in AF. The data are potentially valuable for the scientific community, showing the doubts of different specialists (Internists, Pneumologists, Geriatricians, Cardiologists and Neurologists) with a large experience in prescribing oral anticoagulation in difficult AF and VTE cases (see full list of participants provided). The data obtained in some particular clinical cases such as CHA2DS2-VASc=1, comorbid coronary artery disease, frailty, advanced age, risk of falling and prior haemorrhagic stroke, can be compared with indications from published guidelines and recommendations for future insight and to be considered as a benchmark for future trials in the area or oral anticoagulation for AF and VTE. The data concerning informative campaign on antithrombotic therapy for stroke prevention showed the expert panel agreement on the inclusion of self monitoring of heart rhythm by pulse taking in subjects older than 64 years of age (81% agreement, item 3); knowledge that the risk of stroke associated with AF is almost twice the risk associated with hypertension (95% agreement, item 4); knowledge that the CHA2DS2-VASc score exerts a higher influence on stroke risk compared to AF duration (92% agreement, item 5); knowledge that stroke prevention in AF with a NOAC is more effective, does not cause any higher bleeding risk, and is equally simple compared to aspirin treatment (91% agreement, item 6). Data on strategies to optimise appropriate prescription of antithrombotic therapy showed agreement on the utility of short television advertisements about the risks of stroke associated with AF (79% agreement, item 8), on a campaign encouraging regular control of cardiac rhythm by pulse taking (77% agreement, item 1), on a campaign reporting the advantages of anticoagulation over no antithrombotic therapy (98% agreement, item 2) or of NOACs over aspirin (96% agreement, item 3) or on the practical use of NOAC (93% agreement, item 6) or on stroke and bleeding risk scores (87% agreement, item 7). See Colonna et al. (2017) [1] for further interpretation and discussion.

Primary thromboprophylaxis with low-dose aspirin and antiphospholipid antibodies: Pro's and Con's.

Whether primary prophylaxis should be prescribed in individuals with antiphospholipid antibodies (aPL) remains controversial due to the lack of relevant evidence-based data. Indeed, it is unclear whether the benefit of LDA outweighs the risk of major bleeding associated with LDA in a low-risk population. On the contrary, stratification of aPL-positive subjects according to their aPL profile (combination, isotype and titer), presence of other concomitant risk factors for thrombosis and coexistence of an underling autoimmune disease is essential to decide whether primary prophylactic therapy should be prescribed. Additionally, the management of modifiable thrombotic risk factors is a necessary strategy, and the use of transient prophylaxis is crucial during high-risk periods. Specifically designed prospective trials are urgently needed to determine the real prophylactic impact of aspirin, as well as of alternative or concomitant therapeutic strategies such as hydroxychloroquine, statins or DOACS in aPL positive patients.

Diagnosis and therapy of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a clinical condition that has not been well defined yet. Although the clinical component is well established, the laboratory part is a mood issue. According to current guidelines, 3 tests (lupus anticoagulant, anticardiolipin, and anti ß2-glycoprotein I antibodies) are officially recommended to assess the presence of antiphospholipid antibodies. According to test positivity, patients are classified into categories in clinical studies. However, it is now clear that classification categories have a different impact on the clinical course of APS. Indeed, patients and healthy carriers with a full positive antibody profile (triple positivity) are those at the highest risk of events. Patients with a single test positivity are those at a lower risk. In this review, on the basis of a laboratory profile, we grade the diagnosis of APS into definite, probable/possible, and uncertain. We also discuss secondary prevention of thrombotic APS, prevention of pregnancy morbidity, and treatment of catastrophic APS. Finally, new tools in laboratory diagnosis and treatment are highlighted.

Clinical management of rivaroxaban-treated patients.

INTRODUCTION: Until recently, only vitamin K antagonists (VKAs) were used for long-term anticoagulation. New oral anticoagulants, with pharmacokinetic and pharmacodynamic characteristics different to VKAs, are now available for some indications. Rivaroxaban (Xarelto®) is an oral Factor Xa inhibitor approved in many countries for long-term treatment of patients with atrial fibrillation or venous thromboembolism. This article is addressed to all professionals involved in the management of treated patients to highlight the characteristics of rivaroxaban and provide practical guidance on management of treated patients. AREAS COVERED: This article is based on a consensus of specialists involved in the management of anticoagulant treatment, including thrombosis experts, cardiologists, neurologists, emergency medicine specialists, and general practitioners. The authors performed a nonsystematic review of the literature, and expressed guidance statements based on the results of the review as well as personal experience. EXPERT OPINION: Availability of new anticoagulant drugs, including rivaroxaban, is an important step forward to allow easier, more effective, and safer long-term anticoagulation in patients in whom adequate anticoagulation is currently denied due to the limitations of VKAs. However, given their totally new properties, associated risks, and expected broad clinical use, expert professionals and manufacturers must urgently tackle a series of issues.

Recovery from catastrophic antiphospholipid syndrome by a plasma exchange procedure: report of four cases and review of the literature.

Catastrophic Antiphospholipid Syndrome (CAPS) is a rare (1%), life-threatening variant of Antiphospholipid Syndrome (APS). It has been found that the recovery rate is best when the treatment protocol includes anticoagulants, steroids and therapeutic plasma exchange (TPE). The treatment of CAPS with TPE is not, however, well defined as procedure modalities have not yet been standardized, and the best replacement fluid for TPE is still a controversial issue. Although the most commonly used one, fresh frozen plasma (FFP), contains natural anticoagulants, it is also made up of clotting factors, complement activation products and cytokines which could worsen CAPS' "thrombotic storm". The successful management of 4 CAPS patients, including TPE sessions initiated in the 1st week from diagnosis and using albumin solution as the replacement fluid, is described here. TPE was performed daily for the first 3 days, then tapered off, and withdrawn on the basis of patient's clinical condition. One of the patients was also treated with anticoagulants, while the others received anticoagulants plus high doses of steroids in addition to TPE. Our results indicate that, when initiated promptly and albumin solution is used as the replacement fluid, TPE can be considered an effective, safe treatment for CAPS.