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Background: Idraparinux is a synthetic pentasaccharide that binds to antithrombin with high affinity. In view of its long half-life, it is suitable for once-a-week administration., Objective: To review the evidence favoring the use of idraparinux for the acute and long-term treatment of patients with venous thromboembolism (VTE) and for the prevention of thromboembolic events in patients with atrial fibrillation (AF)., Methods: All preclinical and clinical studies carried out with the use of idraparinux were sought through electronic searches of MEDLINE from January 1, 1999 up to December 31, 2007., Results: The administration of idraparinux in subcutaneous fixed doses of 2.5 mg once weekly was found to be as effective and safe as conventional antithrombotic therapy in the initial treatment of patients with deep vein thrombosis, but less effective than standard therapy in the initial treatment of patients with primary pulmonary embolism. During a 6-month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent VTE but was associated with an increased risk of bleeding versus placebo. Finally, in patients with AF the long-term treatment with idraparinux was as effective as vitamin K antagonists, but caused more bleeding., Conclusions: In its current formulation, idraparinux can be recommended only for the initial treatment of patients with deep vein thrombosis. The bioequipotency of a biotinylated version of idraparinux (idrabiotaparinux), whose effects can be reversed by a neutralizing agent (avidin), is under investigation in the treatment of VTE at present, as is the use of lower doses in patients with AF.

The term thrombophilia includes any inherited and acquired disorders associated with an increased tendency to venous thromboembolism (VTE). Inherited thrombophilia is one of the main determinants of VTE, and the presence of inherited thrombophilic defects exposed carriers to increased risks for VTE compared with noncarriers. There is no clear relationship between clinical manifestations and the type of underlying thrombophilic defect. Thus, the diagnosis of inherited thrombophilia has to be established on a laboratory basis. Carriers of thrombophilic defects may experience thrombosis at a younger age than noncarriers. However, a first thrombotic manifestation that occurs late in life may also be an expression of thrombophilia and this remains in many cases the only etiopathogenetic explanation for the event. Screening of family members of symptomatic probands has the potential to identify still asymptomatic carriers who may benefit from more appropriate thromboprophylaxis during high-risk situations for VTE. Women of fertile age who belong to these thrombophilic families might receive the greatest advantage from screening. Many inherited thrombophilic disorders can be considered risk factors for recurrent VTE, especially if more than one defect is present in the same patient. More intensive or prolonged duration of VTE treatment might be requested for the prevention of recurrent VTE in the most severe thrombophilic conditions. The availability of new methods for the assessment of thrombin generation in terms of endogenous thrombin potential are very promising tools for the identification of those carriers of inherited thrombophilia who will develop thrombosis or who will encounter recurrence of VTE.

Oral contraceptives (OC) are a definite risk for venous thrombosis. It is commonly accepted that they cause a fourfold increased risk of thrombosis compared to non-users. The prescription patterns were evaluated from 1990 to 2000 in a northern Italian province (province of Padua). This province is typical of other northern Italian provinces. As a consequence, it can be safely assumed that the observations gathered may apply to the entire north of Italy. During these years, a sharp increase in the use of OC was noted. Furthermore, around 1995 to 1996, a marked switch toward the use of preparations containing third-generation progestins was noted. During the past few years of the observation period, approximately 80% of women use preparations containing third-generation progestins. During the same period, an increased incidence of episodes of venous thromboembolism (VTE) was noted. The increase in the prevalence of VTE episodes appeared to be proportional to the increased use of OC, regardless of the type of progestin contained in the oral contraceptive preparations.

Oral contraceptive therapy (OCT) is associated with a fourfold increase in the risk for venous thromboembolism (VTE). Women with congenital defects have a much higher risk. Because it is impossible to screen all women undergoing OCT, it is advisable to adopt some guidelines in an attempt to define the group of women who may be particularly exposed to the risk of VTE. On the basis of experience and that in the literature, two flow charts are used that are simple and reliable. The two flow charts are based on an accurate family and personal history so that an extensive investigation can be carried out only for women who show a positive family or personal history for idiopathic thrombosis. The definition of idiopathic thrombosis may be difficult, particularly in the case of family members. In case of doubt the thrombotic event should be considered as idiopathic. The two flow charts are not intended to eliminate the OCT-related VTE but represent only an attempt to decrease the prevalence of this complication.

The incidence of venous thromboembolism (VTE) in the pediatric population has increased more than 10-fold in the last 20 years, as a consequence of the advancement of resuscitation and surgical techniques and the global increase in life expectancy of children suffering from chronic pathologies. Monitoring anticoagulant therapy to achieve outcomes within the target range in childhood VTE, parenteral administration of medications, and frequent blood tests in children are often cumbersome. Availability of safe and effective oral agents with pediatric data to support use would be of clear benefit. A physiologically based pharmacokinetic model was developed to estimate the appropriate dosing schedule for rivaroxaban in children. This incorporated growth/maturation and variability in anthropometrics (e.g., body height, weight, and body mass index), anatomy (e.g., organ weight), physiology (e.g., blood flow rates), metabolism and excretion. Rivaroxaban use in pediatric population underwent a complete investigational program, consisting mainly of one phase I pharmacokinetics/pharmacodynamics trial, three phase II trials, one phase III trial. The phase III trial enrolled 500 patients from birth to <18 years and documented the efficacy and safety of rivaroxaban regimens at dose equivalent to the adult 20 mg dose for the prevention of fatal or symptomatic nonfatal recurrent VTE and major bleeding versus heparin or vitamin K antagonists. Results were similar to those in rivaroxaban studies in adults. The efficacy and safety of rivaroxaban in children reported in the EINSTEIN JUNIOR trial provide further support to previous trials in adults (EINSTEIN Program), which demonstrate a favorable profile for the use of rivaroxaban for the management of VTE in challenging patient populations. Other clinical evidence contributing to the use of rivaroxaban among different risk groups in pediatric VTE population confirms the consistency with principal trial. Our review aims to describe the rationale for using rivaroxaban oral suspension in clinical practice and to summarize its multiple indications in each vascular bed (e.g., cerebral venous thrombosis, symptomatic or asymptomatic central venous catheter-associated thrombosis), etiology, and patients setting. [ABSTRACT FROM AUTHOR]

Transthyretin amyloidosis (ATTR) is a group of diseases caused by the deposition of insoluble fibrils derived from misfolded transthyretin, which compromises the structure and function of various organs, including the heart. Thromboembolic events and increased bleeding risk are among the most important complications of ATTR, though the underlying mechanisms are not yet fully understood. Transthyretin plays a complex role in the coagulation cascade, contributing to the activation and regulation of the coagulation and fibrinolytic systems. The prevalence of atrial fibrillation, cardiac mechanical dysfunction, and atrial myopathy in patients with ATTR may contribute to thrombosis, though such events may also occur in patients with a normal sinus rhythm and rarely in properly anticoagulated patients. Haemorrhagic events are modest and mainly linked to perivascular amyloid deposits with consequent capillary fragility and coagulation anomalies, such as labile international-normalised ratio during anticoagulant therapy. Therefore, it is paramount to carefully stratify the thrombotic and haemorrhagic risks, especially when initiating anticoagulant therapy. Our review aims to ascertain the prevalence of thromboembolic and haemorrhagic events in ATTR and identify potential risk factors and predictors and their impact on antithrombotic therapy. [ABSTRACT FROM AUTHOR]

Background: Therapeutic/intermediate-dose heparin reduces the risk of thromboembolic events but increases the risk of major bleeding in patients hospitalized for acute COVID-19 pneumonia. Objectives: To prospectively assess the incidence of objectively proven venous thromboembolism (VTE) and identify predisposing risk factors in a cohort of hospitalized patients with acute COVID-19 pneumonia undergoing prophylactic-dose heparin. Patients and methods: All consecutive patients admitted for acute COVID-19 pneumonia to the General Internal Medicine Unit of Padova University Hospital, Italy between November 2020 and April 2021, and undergoing prophylactic-dose heparin, were enrolled. Demographic and clinical characteristics and laboratory and radiological findings were recorded on admission. Cases were patients who developed VTE during their hospital stay. Univariable and multivariable logistic regression analyses were used to ascertain the risk factors associated with developing in-hospital VTE. Results: 208 patients (median age: 77 years; M/F 98/110) were included; 37 (18%) developed in-hospital VTE during a median follow-up of 10 days (IQR, 4–18). VTE patients were significantly younger (p = 0.004), more obese (p = 0.002), and had a lower Padua prediction score (p < 0.03) and reduced PaO2/FIO2 ratio (p < 0.03) vs. controls. Radiological findings of bilateral pulmonary infiltrates were significantly more frequent in VTE patients than controls (p = 0.003). Multivariable regression showed that obesity (1.75, 95% CI 1.02–3.36; p = 0.04) and bilateral pulmonary infiltrates on X-rays (2.39, 95% CI 1.22–5.69; p = 0.04) were correlated with increased risk of in-hospital VTE. Conclusions: Obesity and bilateral pulmonary infiltrates on imaging may help clinicians to identify patients admitted to medical wards for acute COVID-19 pneumonia at risk of developing VTE despite prophylactic-dose heparin. Further studies are needed to evaluate whether the administration of therapeutic/intermediate-dose heparin may help prevent VTE episodes without further increasing the bleeding risk. [ABSTRACT FROM AUTHOR]

Glucocorticoids are potent anti-inflammatory agents that are widely used for the treatment of many inflammatory, autoimmune, and neoplastic disorders. However, their beneficial effect is associated with several side effects, including an increased risk of cardiovascular complications, such as myocardial infarction and stroke. Whether their use also contributes to a procoagulant state, and therefore increases the risk of venous thromboembolism (VTE), is still a matter of debate. As an increased risk of venous thrombotic events is described in patients with Cushing's syndrome, which is characterized by endogenous hypercortisolism, it is reasonable to speculate that the chronic administration of glucocorticoids may induce a hypercoagulable state. However, it seems virtually impossible to separate the role of the drug from the underlying condition, which itself predisposes to the development of VTE. Actually, some evidence suggests that the use of exogenous glucocorticoids for the treatment of underlying disease and its exacerbations may further amplify the risk of VTE. Moreover, a procoagulant state has also been reported in healthy participants receiving oral glucocorticoids versus placebo. We have performed a concise narrative review on available data on the influence of exogenous glucocorticoids on hemostasis and their clinical impact on the risk of VTE. [ABSTRACT FROM AUTHOR]

Despite thromboprophylaxis, patients with coronavirus disease 2019 (COVID‐19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with COVID‐19 admitted to both intensive care units (ICUs) and medical wards (MWs). Consecutive patients admitted for COVID‐19 to the MW and the ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of the internal jugular, and the upper and lower limbs veins every 7 days (± 1 day) after the admission; and, if negative, once‐weekly until discharge or death. In case of suspected pulmonary embolism, a multidetector computed tomographic angiography was performed. The primary outcome was the proportion of any deep‐vein thrombosis (DVT) and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020, a total of 85 patients were investigated, 44 (52%) in MWs and 41 (48%) in the ICU. Despite thromboprophylaxis, VTE occurred in 12 patients in the MWs (27.3%) and 31 patients in the ICU (75.6%) with an odds ratio of 9.3 (95% confidence interval (CI) 3.5–24.5; P < 0.001). Multiple‐site DVT occurred in 55.6% of patients (95% CI 39.6–70.5). Increased D‐dimer levels significantly correlated with VTE (P = 0.001) and death (P = 0.015). Summarizing, patients with COVID‐19 admitted to the MW or ICU showed a high frequency of venous thromboembolism, despite standard‐dose or high‐dose thromboprophylaxis. Whether thrombosis, particularly asymptomatic events, may play a role in the morbidity and mortality of patients with COVID‐19 remain to be clarified. [ABSTRACT FROM AUTHOR]

Over the past decades, there have been great advances in the understanding of the pathogenesis of venous thromboembolism (VTE) in patients with inherited and acquired thrombophilia [mainly antiphospholipid antibody syndrome (APS)]. However, a number of questions remain unanswered. Prognostic markers capable of estimating the individual VTE risk would be of great use. Microparticles (MPs) are sub-micron membrane vesicles constitutively released from the surface of cells after cellular activation and apoptosis. The effects of MPs on thrombogenesis include the exposure of phopshatidylserine and the expression of tissue factor and MPs have been described in clinical studies as possible diagnostic and prognostic biomarkers for VTE. This review will provide a novel perspective on the current knowledge and research trends on the possible role of MPs in hereditary thrombophilia and APS. Basically, the published data show that circulating MPs may contribute to the development of VTE in thrombophilic carriers, both in mild and severe states. Moreover, the presence of endothelial-MPs and platelet- MPs has been described in antiphospholipid syndrome and seems to be directly linked to antiphospholipid antibodies and not to other underlying autoimmune disorders or the thrombotic event itself. In conclusion, circulating MPs may constitute an epiphenomenon of thrombophilia itself and could be up-regulated in acute particular conditions, promoting a global prothrombotic state up to the threshold of the clinical relevant thrombotic event. [ABSTRACT FROM AUTHOR]

The association between air pollution exposure and occurrence of venous thromboembolism is a matter of debate. This retrospective case-control study investigated the associations between one month's exposure to elevated levels of different pollutants (i.e. PM10, CO, NOx, O3, SO2, Benzene, Benzoapyrene, Nickel, Lead Arsenic) and the development of acute isolated pulmonary embolism (PE). Methods The cases included 33 patients consecutively admitted to Padua Hospital with an objectively proven diagnosis of acute unprovoked (i.e. without predisposing conditions) isolated (i.e. without deep vein thrombosis) PE. The control group consisted of 72 consecutive patients with objectively proven acute provoked (i.e. associated to predisposing conditions) isolated PE. Average mean concentrations of pollutants in the month before PE diagnosis were computed by monitors located at 2 different sites throughout the city of Padua, and were obtained from the Regional Agency for Environmental Protection. Results Individuals who had PM10, NOx, Benzene, Benzoapyrene, Cadmium, and Lead exposure equal/above the 2nd tertile, measured in controls, showed a significant increase in the risk of unprovoked PE. In case of PM10 and Benzoapyrene this risk was not affected after adjustment for possible confounders. In fact, in the multivariate logistic regression analysis, the OR values were 5.24 (95% CI: 1.52-18.12) for PM10 and 3.95 (95% CI: 1.06-14.71) for Benzoapyrene exposure in the month before PE diagnosis. Conclusions Our results, although preliminary, identify short-term (i.e. one month) exposure to elevate levels of air pollutants as a possible risk factor for the development of acute isolated PE. Larger studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagnlation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulatiom while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE. [ABSTRACT FROM AUTHOR]