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The indications for the use of aspirin in primary cardiovascular prevention continue to be a source of intense debate, with major international guidelines providing conflicting advices. This document, written by delegates of the main Italian scientific societies dealing with cardiovascular prevention and modeled on a similar document by the European Society of Cardiology Working Group on Thrombosis, reviews the evidence in favor and against the use of aspirin therapy in primary prevention based on data cumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, this document argues for a pragmatic approach to the use of low-dose aspirin in primary cardiovascular prevention, and suggests its use in patients at high cardiovascular risk, defined as ≥2 major cardiovascular events (death, myocardial infarction, or stroke) projected per 100 person-years, who are not at increased risk of bleeding.

While the use of aspirin in the secondary prevention of cardiovascular atherothrombotic disease is well established, many aspects of primary prevention are still unclear. Uncertainties mostly depend on a doubtful risk-benefit ratio, because of the low atherothrombotic risk of populations involved on the one hand, and the non-negligible bleeding risk of treatment on the other. Areas of specific doubt are those of diabetes and asymptomatic peripheral arterial disease, where neither single trials nor meta-analyses allow issuing high-grade specific recommendations at the moment. The present review aims at giving an account on this topic, highlighting areas for further studies, but also attempting at providing a rationale for what to do practically now, while awaiting more conclusive evidence. Based on the results of a number of clinical trials and meta-analyses, and especially considering the absolute figures of the benefit (major cardiovascular events avoided) and of the harm (major bleeding events occurred related to aspirin), the authors recommend to limit primary cardiovascular prevention with aspirin (in apparently healthy subjects with no previous cardiovascular events) to subjects with an estimated global cardiovascular risk ≥2 major cardiovascular events per 100 patients-year, as assessed by the risk score assessments proposed in the Italian "Progetto Cuore" (www.progettocuore.it). This cut-off should also be adopted for primary prevention in patients with type 2 diabetes and/or asymptomatic peripheral arterial disease.

Background: Clinical diagnosis of deep venous thrombosis (DVT) of the leg is unreliable. An accurate diagnosis is important for therapeutic decision since anticoagulant treatment, though potentially dangerous, is useless in case of a false positive diagnosis, whereas a false negative diagnosis may lead to withdrawal of an extremely necessary anticoagulation. Contrast venography is still recognized as the gold standard method for the diagnosis of DVT, but in recent years a variety of accurate non-invasive methods has been developed. The ultrasound compression sonography (CUS) is considered a simple non invasive test highly sensitive and specific for proximal DVT in symptomatic outpatients, though non adequately sensitive and specific for isolated calf DVT. Plasma D-dimer levels (DD, fibrin degradation products) have a high negative predictive value for DVT. The aim of this study, performed in outpatients with suspected leg DVT, was to validate, versus venography, a non-invasive, easy to perform and fast diagnostic procedure based on a combination of CUS and D-dimer test. End points of the procedure were: confirmation or exclusion of proximal DVT; suspicion of isolated calf DVT in which case the test would be repeated in a few days to detect any possible proximalization of thrombosis., Materials and Methods: Sixty-eight consecutive outpatients, 37 male, with clinically suspected first episode of leg DVT were eligible and examined with CUS, DD test and venography., Results: The results showed that the diagnostic procedure under examination has a high sensibility and specificity for DVT., Conclusions: It can thus be recommended as routine diagnostic procedure in symptomatic outpatients with suspected DVT reserving venography special cases only.

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.

Deep vein thrombosis (DVT), if not properly treated, may be complicated by pulmonary embolism in about 50% of the cases within 3 months. Therefore, effective prevention of pulmonary embolism relies on three cornerstones: correct prophylaxis, early diagnosis, and correct treatment of DVT. In prophylaxis of DVT, low-dose heparin is effective in preventing postoperatory DVT and pulmonary embolism in medium risk operations, and also in "medical" DVT. In high risk operations and patients, personalized low-dose heparin, oral anticoagulants and especially low-molecular weight heparins have been used. The available controlled trials demonstrate that the low-molecular weight heparins are especially efficacious and also cost-effective in high risk situations as elective hip surgery. Validated techniques for early diagnosis of DVT are phlebography and, in symptomatic proximal DVT, also venous echotomography. Therapy of overt DVT is usually performed with infusional or subcutaneous heparin at therapeutic doses, followed by moderate range oral anticoagulants. In the initial treatment, low-molecular weight heparins at single subcutaneous daily dosing can substitute for standard heparin. Indication to thrombolytic therapy should be restricted to selected cases; thrombectomy has limited application. Caval filters may be useful in strictly selected indications, especially in presence of contraindications or resistance to anticoagulant treatments.

During the last decade interesting data have been collected on the epidemiological significance of some coagulation factors as risk indices for major cardiovascular events and, also, for the prognosis of atherothrombotic disease. The factors for which evidence is most convincing include: plasma fibrinogen, coagulation factor VII, and an inhibitor of fibrinolysis, namely the plasminogen activator inhibitor PAI-1. These data have been provided by studies of primary predictivity, in which the said parameters were measured in healthy subjects whose cardiovascular outcome was followed. Studies of secondary predictivity, or prevalence studies have also been extremely helpful. In these, the coagulation factors measured in patients already suffering from atherothrombotic disease were correlated with its severity, extension and outcome. From these data, the plasma fibrinogen level emerges as the coagulation parameter best correlated with cardiovascular events, that is, as both a primary and a secondary predictor. The predictive power of plasma fibrinogen level appears to be no less significant than that of blood cholesterol. Although a few methodological problems must still be overcome, hyperfibrinogenemia is gaining increasing consideration as a new, important risk factor for cardiovascular events. It is however premature to consider the said parameters not only as risk indices but also as causal factors of atherothrombotic disease. In fact, their pathogenic and causal role, although supported by high biological plausibility, has not yet been confirmed by interventional studies aimed at assessing whether or not therapeutic lowering of these values is associated with reduced cardiovascular risk.

The rationale of the hemorheologic approach to the pathophysiological knowledge and to the treatment of obstructive arterial diseases of the limbs is discussed in this paper. Indeed, the hemodynamic concepts are the natural frame in which the hemorheologic phenomena have to be considered. Proceeding from this background, it seems evident that the viscosity of blood and its major determinants have a limited role in the regulation of blood flow and pressure gradient through a stenotic artery. On the contrary, viscosity factors are of outstanding significance in the regulation of blood flow in the microcirculation, especially in presence of a reduced perfusion pressure and of exhausted arteriolar vasodilation capacity. Consequently, therapeutic measures capable of modifying one or more viscosity determinants may improve blood flow in the microcirculation of territories related to a stenotic artery. Baseline alterations of viscosity or viscosity determinants may be found in patients with obstructive arterial disease, being classified as primary, associated or secondary to arterial obstruction and ischemic damage. However, the presence of such baseline changes is not relevant to the indication of hemorheologic treatments.