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Diagnosis of antiphosholipid syndrome (APS) is based on laboratory detection of antiphospholipid (aPL) antibodies in patients with documented thrombosis or in women with pregnancy morbidity. Recently, both clinical and laboratory criteria were revised on the basis of an international consensus conference held in Sydney (1). The previous international consensus statement of one clinical and one laboratory criterion to diagnose APS was maintained (2) but time-lapse between the previous thromboembolism and laboratory diagnosis should not exceed 5 years. Moreover, laboratory tests should not be performed in the 12 weeks following the event to avoid any interference of the acute phase of the disease. Thus, laboratory evaluation of venous thromboembolism (VTE) should not be requested during the hospital stay as tests may be false-positive with no influence on the treatment regimen...

In the last decade, direct oral anticoagulants (DOACs) have entered the clinical practice of different specialists for the prevention of cardioembolic stroke in patients with non-valvular atrial fibrillation (NVAF) and the prevention and treatment of venous thromboembolism (VTE). Owing to the persistent uncertainties about the use of DOACs in daily clinical scenarios not fully explored in the clinical trials, we conducted a national Delphi consensus regarding issues deemed interesting by the Italian Atherosclerosis, Thrombosis and Vascular Biology (ATBV) Study Group in relation to: (i) elderly and/or frail patients; (ii) chronic kidney disease; (iii) drug-drug interactions; (iv) lower doses and safety; (v) criteria for choosing individual drugs and compliance; (vi) VTE in the cancer patient. Eighty-four Italian clinicians (cardiologists, internists, geriatricians, neurologists and hematologists) expressed their level of agreement on each statement using a 5-point Likert scale (1: very much in disagreement, 2: disagreement, 3: partial agreement, 4: agreement, 5: very much in agreement). In particular, 1-2 selections were considered as disagreement, while 3-5 selections were considered as agreement. A ≥66% agreement between the participants for each statement was considered consensus. In general, a broad and general awareness and sharing of the methods of use of DOACs emerged from our initiative, and in particular their preferential indication in the elderly population and in frail patients or with renal insufficiency or oncological, always following the prescription indications and dose reduction criteria. The importance of being aware of drug-drug interactions has also been underlined in a concordant way, as well as simplicity of treatment in the multi-treated patient. In view of the persistent, albeit limited (12%), absence of consensus on some issues, with regard to the frail patient, drug-food interactions and availability of antidote, the acquisition of further evidence and a persistent educational effort are nonetheless indicated.

Given the high prevalence of preexisting cardiovascular diseases and the increased incidence of adverse cardiovascular events in patients hospitalized for SARS-CoV-2 infection, the identification of optimal antithrombotic approaches in terms of risk/benefit ratio and outcome improvement appears crucial in this setting. In the present position paper we collected current evidence from the literature to provide practical recommendations on the management of antithrombotic therapies (antiplatelet and anticoagulant) in various clinical contexts prevalent during the SARS-CoV-2 outbreak: in-home management of oral anticoagulant therapy; interactions between drugs used in the SARS-CoV-2 infection and antithrombotic agents; in-hospital management of antithrombotic therapies; diagnosis, risk stratification and treatment of in-hospital thrombotic complications.

In this paper we demonstrate that among four phase III trials comparing warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) vs warfarin in patients with non-valvular atrial fibrillation there was heterogeneity in the thromboembolic and bleeding risk of the included populations, variability in the definitions of primary endpoints, especially for safety, and different criteria for reducing NOAC dosage according to renal function. Therefore, findings from these four studies are not directly comparable and it is incorrect to conduct comparative evaluations between various NOACs. In each patient the antithrombotic strategy should be tailored taking into account NOAC characteristics, the individual thromboembolic and bleeding risk, presence of comorbidities, mental status and socio-economic conditions.

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, particularly in the elderly. AF is considered an independent predictor of mortality and risk factor for stroke. AF-related stroke is usually severe and associated with a high rate of mortality and disability. Despite its prevalence, AF is a poorly known disease and it is underestimated by the general population. The aim of the Censis survey was to analyze the levels of AF knowledge and information in the Italian population and the level of AF risk awareness by general practitioners and AF patients., Methods: The survey included structured interviews with a sample of 1000 Italian citizens aged ≥18 years, 300 general practitioners, and 1200 AF patients., Results: The analysis confirmed low levels of knowledge of AF. In particular, the results showed that only one third of Italians know AF that is however perceived as a severe disease. In this subgroup, the risk of stroke associated with AF is known by 65%, but it is also widespread the wrong concept that AF is associated with an increased risk of myocardial infarction. The lack of knowledge of AF and its complications by the Italian population is due to educational gaps of general practitioners. In particular, only 50% of the Italian general practitioners perceive the thromboembolic risk of paroxysmal AF as comparable to that of permanent AF. In addition, there is an underuse of the scores for thromboembolic and hemorrhagic risk stratification recommended by current guidelines and a frequent use of antiplatelet therapy rather than oral anticoagulant therapy. There is also a low level of knowledge and awareness of the disease among AF patients. However, the majority of AF patients are aware of the importance of antithrombotic prophylaxis for stroke prevention., Conclusions: This study demonstrates limited knowledge and awareness of AF in the general population and also among general practitioners and affected patients.

In recent years oral anticoagulant therapy has been recommended to an increasing number of patients for the primary or secondary prevention of thromboembolic diseases. Optimal management includes patient's education, adequate laboratory and specific clinical control. In this review, together with basic knowledge, data from medical literature are used to provide guidelines and practical information for the management of these patients.

Randomized clinical trials have demonstrated the efficacy and safety of oral anticoagulants in the prevention of systemic thromboembolism in nonrheumatic atrial fibrillation. The benefit of this treatment is particularly evident in patients in whom atrial fibrillation is associated with a major risk factor for systemic thromboembolism (patients > 75 years of age, history of hypertension, previous left ventricular failure or previous systemic thromboembolism) or those in whom two minor risk factors are present (patients between 65 and 75 years of age, diabetes, ischemic heart disease). According to these recommendations, all the patients > 75 years of age with chronic or paroxysmal atrial fibrillation should receive oral anticoagulant treatment to maintain an INR between 2.0 and 3.0. However, as the risk of bleeding during oral anticoagulant treatment increases with age, the benefit/risk ratio should always be evaluated in elderly patients. Although high risk patients do not benefit from aspirin treatment, aspirin or other antiplatelet agents might be indicated in medium risk patients or in those in whom the risk of bleeding with oral anticoagulants is considered too high. New antithrombotic regimens will be tested in the near future.

Background: To assess the incidence of bleeding complications during oral anticoagulant therapy (OAT) in a population of patients representative of daily practice in Italian anticoagulation clinics., Design: prospective, inception-cohort, multicentre., Setting: Thirty-four anticoagulation clinics federated in the Italian Federation of Anticoagulation Clinics., Patients: 2745 consecutive patients, included from beginning of their first OAT course. Most patients were aged between 60 and 79 y (57.8%), with 8% being > or = 80 y. Venous thromboembolism was the most frequent indication for OAT (one third of all the patients), followed by non ischemic heart disease which mainly included atrial fibrillation (16.8% of patients). Warfarin (in 63.8% of patients) and acenocoumarol were the only anticoagulant drugs used. The targeted anticoagulation intensity was low (INR < or = 2.8) in 71% of patients and high (INR > 2.8) in the remainder., Outcomes: Fatal, major and minor bleeding events. Thrombotic events were also recorded, though not analyzed in the present report., Findings: During the 2011 patient-years (pt-y) of follow-up, 153 bleeding complications (7.6% pt-y) were recorded--5 fatal (all cerebral haemorrhages, 0.25% pt-y), 23 major (1.1% pt-y) and 125 minor (6.2% pt-y). The rate of events did not vary according to sex, coumarin type, size of enrolling centre or targeted therapeutic range; it was higher in older patients (10.5% pt-y in those aged > or = 70 y, relative risk--RR--1.75, p < 0.001), in cases where indication for anti-coagulant treatment was peripheral and/or cerebrovascular disease (12.5% pt-y; RR 1.80, p < 0.01) and during the first 90 days of treatment (11% pt-y, RR 1.75, p < 0.001). One fifth of bleeding events occurred at a very low anticoagulation intensity (INR < 2; the category rate being 7.7% pt-y); the rate was 4.8% pt-y in the 2.0-2.9 INR category, reaching 9.5% pt-y, 40.5% pt-y and 200% pt-y in the 3-4.4, 4.5-6.9 and > or = 7 INR categories respectively (RR for INR levels > 4.5 = 7.91, p < 0.0001)., Conclusions: The overall rate of bleeding events recorded in the present study was much lower than that recorded in other (including recent) observational and experimental studies. The risk of bleeding increased in the following cases: age > 70 y; arterial vascular disease as indication for OAT; first 3 months of treatment; INR values > or = 4.5. OAT has become safer in recent years, particularly if monitored in special anticoagulation clinics. Caution should be exercised when prescribing OAT in elderly patients and the intensity anticoagulation levels should be closely monitored to minimize incidental periods of overanticoagulation.

In patients with artificial heart valve prosthesis oral anticoagulants reduce but not eliminate the thromboembolic complications however, they do increase the risk of bleeding. In the present study, the incidence of thromboembolic and hemorrhagic complications in two homogeneous groups of patients with artificial heart valves on long term oral anticoagulant treatment has been evaluated. Group A (99 patients; total follow-up = 309 years) were resident in the Triveneto regions and received a questionnaire while group B (104 patients; total follow-up = 370 years) were referred to our department's centre for the control of oral anticoagulant treatment. Both groups were kept at a therapeutic range of 20-30% in terms of prothrombin activity. The incidence of thromboembolic and hemorrhagic complications is expressed as the number of episodes per 100 patient/years. Thromboembolic episodes were 2.6 (1.3 fatal) in group A while they were 1.08 (0.27 fatal) in group B; the reduction of fatal thromboembolic events was statistically significant (p less than 0.05). Hemorrhagic episodes were 1.9 (0.63 fatal) in group A while they were 0.81 (0 fatal) in group B. We concluded that an organized control of oral anticoagulant treatment in patients with artificial heart valves is advantageous as it significantly reduces fatal thromboembolism. Moreover, it could reduce the incidence of total thromboembolic and hemorrhagic episodes by more than 50%.

Antithrombin III (AT III) an alpha 2 globulin produced by liver, is the most important plasmatic inhibitor of activated coagulation factors, that bind irreversibly to it with formation of inactive complexes. Therefore, when coagulation processes are activated in vivo, a decrease of AT III is presumably likely to occur. In the present research, AT III has been determined both as substance concentration, by radial immunodiffusion, and on the base of its activity on a chromogenic substrate (Chromozym) in patients with DIC before and after heparin therapy. Some patients with acute liver insufficiency have been similarly studied, because they not only have a deficient protein synthesis but also show phenomena of anticoagulative factors consumption. In all the patients, the AT III levels appeared decreased by both methods; the decrease of activity was comparatively much more intense and in a case no activity was even detectable.

Eight patients with massive pulmonary thromboembolism documented by angiography were treated with Urokinase (UK) 4.400 IU/Kg/hr for 12 hours. UK i.v. infusion was started immediately after angiographic evaluation (Miller index) and was followed by anticoagulant therapy with heparin and sodium warfarin. All patients survived even though 4 pts. were in shock before treatment. Significant reduction of pulmonary obstruction (reduction of Miller index) was obtained in 7 patients with 48 hours from withdrawal of the drug. Mild superficial bleedings which did not influence the clinical course were the only complication recorded. Neither bleedings nor angiographic improvement showed a correlation with thrombin time prolongation. Indications for thrombolytic therapy of pulmonary embolism and particularly prevention of the major haemorrhagic complications are briefly discussed. It is concluded that the high doses of UK suggested by Food and Drug Administration may be used safely in patients affected by massive pulmonary thromboembolism with or without shock, if patients are adequately selected and prevention of major haemorrhagic complications is continued throughout treatment.

The fibrin/fibrinogen degradation products were measured in 24 synovial fluids sampled from patients with knee joint effusion. It has been observed that they are increased in synovial fluid involved in inflammatory processes. Their presence and concentration seem to be related to the control of local inflammation.