Determinants of health-related quality of life: a cross-sectional investigation in physician-managed anticoagulated patients using vitamin K antagonists.

BACKGROUND: Literature has paid little attention in describing the specific contribution of each modifiable and non-modifiable characteristics on health-related quality of life (HRQoL) in physician-managed anticoagulated patients using vitamin K antagonists (VKAs). To describe how patients' treatment-specific knowledge, health literacy, treatment beliefs, clinical, and socio-demographic characteristics influence HRQoL in Italian physician-managed anticoagulated patients using VKAs. METHODS: Cross-sectional multicentre study with a consecutive sampling strategy, enrolling 164 long-term anticoagulated patients. Clinical and socio-demographic characteristics were collected from electronic medical records. Valid and reliable questionnaires were used to collect patients' treatment-specific knowledge, health literacy, beliefs about VKAs, physical and health perceptions. RESULTS: Obtaining and understanding health information (i.e., communicative health literacy) positively predicts both adequate mental (ORadjusted = 10.9; 95%CI = 1.99-19.10) and physical (ORadjusted = 11.54; 95%CI = 1.99-34.45) health perceptions. Conversely, the ability to perform proper health decision making (i.e., critical health literacy) was associated with lower rates of adequate mental health perception (ORadjusted = 0.13; 95%CI = 0.03-0.63). Further, age negatively predicted physical health perception (ORadjusted = 0.87; 95%CI = 0.81-0.93). CONCLUSIONS: Health literacy plays an interesting role in predicting HRQoL. The relationship between critical health literacy and mental health perception could be influenced by some psychological variables, such as distress and frustration, which could be present in patients with higher levels of critical health literacy, as they could be more inclined for self-monitoring. For this reason, future research are needed to identify the most suitable patients' profile for each OAC-management model, by longitudinally describing the predictive performance of each modifiable and non-modifiable determinant of HRQoL.

Harmful and Beneficial Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis.

BACKGROUND & AIMS: Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis. METHODS: We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension-related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls. RESULTS: The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper-gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension-related event-free and transplantation-free survival times. CONCLUSIONS: In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension-related, event-free, and transplantation-free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.

Thrombophilic risk of individuals with rare compound factor V Leiden and prothrombin G20210A polymorphisms: an international case series of 100 individuals.

The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis-free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE.

Aspirin for preventing the recurrence of venous thromboembolism.

BACKGROUND: About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown. METHODS: In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome. RESULTS: Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups. CONCLUSIONS: Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677.).

Management of DOAC in Patients Undergoing Planned Surgery or Invasive Procedure: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. About a quarter of the anticoagulated patients require temporary cessation of direct oral anticoagulants (DOACs) or vitamin K antagonists for a planned intervention within 2 years from anticoagulation inception. Several clinical issues about DOAC interruption remain unanswered: many questions are tentatively addressed daily by thousands of physicians worldwide through an experience-based balancing of thrombotic and bleeding risks. Among possible valuable answers, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) proposes some experience-based suggestions and expert opinions. In particular, FCSA provides practical guidance on the following issues: (1) multiparametric assessment of thrombotic and bleeding risks based on patients' individual and surgical risk factor, (2) testing of prothrombin time, activated partial thromboplastin time, and DOAC plasma levels before surgery or invasive procedure, (3) use of heparin, (4) restarting of full-dose DOAC after high risk bleeding surgery, (5) practical nonpharmacological suggestions to manage patients perioperatively. Finally, FCSA suggests creating a multidisciplinary "anticoagulation team" with the aim to define the optimal perioperative management of anticoagulation.

Different Lung Parenchyma Quantification Using Dissimilar Segmentation Software: A Multi-Center Study for COVID-19 Patients.

BACKGROUND: Chest Computed Tomography (CT) imaging has played a central role in the diagnosis of interstitial pneumonia in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be used to obtain the extent of lung involvement in COVID-19 pneumonia patients either qualitatively, via visual inspection, or quantitatively, via AI-based software. This study aims to compare the qualitative/quantitative pathological lung extension data on COVID-19 patients. Secondly, the quantitative data obtained were compared to verify their concordance since they were derived from three different lung segmentation software. METHODS: This double-center study includes a total of 120 COVID-19 patients (60 from each center) with positive reverse-transcription polymerase chain reaction (RT-PCR) who underwent a chest CT scan from November 2020 to February 2021. CT scans were analyzed retrospectively and independently in each center. Specifically, CT images were examined manually by two different and experienced radiologists for each center, providing the qualitative extent score of lung involvement, whereas the quantitative analysis was performed by one trained radiographer for each center using three different software: 3DSlicer, CT Lung Density Analysis, and CT Pulmo 3D. RESULTS: The agreement between radiologists for visual estimation of pneumonia at CT can be defined as good (ICC 0.79, 95% CI 0.73-0.84). The statistical tests show that 3DSlicer overestimates the measures assessed; however, ICC index returns a value of 0.92 (CI 0.90-0.94), indicating excellent reliability within the three software employed. ICC was also performed between each single software and the median of the visual score provided by the radiologists. This statistical analysis underlines that the best agreement is between 3D Slicer "LungCTAnalyzer" and the median of the visual score (0.75 with a CI 0.67-82 and with a median value of 22% of disease extension for the software and 25% for the visual values). CONCLUSIONS: This study provides for the first time a direct comparison between the actual gold standard, which is represented by the qualitative information described by radiologists, and novel quantitative AI-based techniques, here represented by three different commonly used lung segmentation software, underlying the importance of these specific values that in the future could be implemented as consistent prognostic and clinical course parameters.

Best quality indicator of vitamin K antagonist therapy to predict mortality and bleeding in haemodialysis patients with atrial fibrillation.

BACKGROUND: There is a high prevalence of atrial fibrillation (AF) in patients undergoing haemodialysis. Oral anticoagulant therapy with vitamin K antagonists (VKAs) is the only accepted treatment for the prevention of thromboembolism in haemodialysis patients with AF. However, in this population, the risk of bleeding is greatly increased. The aim of the study was to evaluate the ability of treatment quality indicators of VKA therapy to predict mortality and bleedings in a population of haemodialysis patients with AF. MATERIALS AND METHODS: A total of 129 patients were included in this cohort study. Deaths and bleeding events were recorded during a follow-up of 4 years. In all patients, International Normalized Ratio (INR) values were assessed at least once a month. Time in therapeutic range (TTR) and INR variability, as measured by the standard deviation of INR, were updated at each INR measurement. A Cox model with time-dependent co-variates and sandwich variance was applied. RESULTS: During follow-up, 71 patients died and 55 bleeding episodes occurred in 31 patients. INR variability was the only indicator associated with both mortality (hazard ratio [HR]=1.67, 95% confidence interval [CI] 1.12; 2.49, p=0.012) and bleeding (HR=2.85, 95% CI: 1.71; 4.75, p=0.0001). HR of mortality was higher in patients with INR >3 (HR=2.06, 95% CI: 1.09; 3.88, p=0.0259) than in subjects in therapeutic range 2

The effect of health literacy on vaccine hesitancy among Italian anticoagulated population during COVID-19 pandemic: the moderating role of health engagement.

Assessing vaccine hesitancy and its determinants is pivotal to optimize vaccine acceptance in anticoagulated patients, given that this population has been described to have a higher risk of severe COVID-19-related complications. This study assessed the moderator role of patients' health engagement on the relationship between health literacy and vaccine hesitancy. A web-based survey was performed in Italy during the first wave (June-August 2020) and the second wave (October 2020-March 2021) of the COVID-19 pandemic, enrolling 288 patients. The rates of vaccine hesitancy reported during the first pandemic wave were 38.4% and 30.8% during the second wave (when a vaccine was available) (p = .164). A moderation analysis was performed to assess the role of health engagement in influencing the relationship from health literacy to vaccine hesitancy. Patients' health engagement enhanced the effects of health literacy on decreasing vaccine hesitancy (p < .001), suggesting that co-construction strategies for communicative action are pivotal.

Correction to: Reversal agents for oral anticoagulant-associated major or life-threatening bleeding.

The article Reversal agents for oral anticoagulant-associated major or life-threatening bleeding, written by Marco Moia, Alessandro Squizzato was originally published electronically on the publisher's internet portal (currently SpringerLink) on 24 August 2019 without open access.

Managing anticoagulation in the COVID-19 era between lockdown and reopening phases.

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. The recent spreadout of the COVID-19 pandemic requires a re-organization of Anticoagulation Clinics to prevent person-to-person viral diffusion and continue to offer the highest possible quality of assistance to patients. In this paper, based on the Italian Federation of Anticoagulation Clinics statements, we offer some advice aimed at improving patient care during COVID-19 pandemic, with particular regard to the lockdown and reopening periods. We give practical guidance regarding the following points: (1) re-thinking the AC organization, (2) managing patients on anticoagulants when they become infected by the virus, (3) managing anticoagulation surveillance in non-infected patients during the lockdown period, and (4) organizing the activities during the reopening phases.

A multicentre randomised assessment of the DAWN AC computer-assisted oral anticoagulant dosage program.

Computer-assisted oral anticoagulant dosage is being increasingly used to meet growing demands for oral anticoagulation. The DAWN AC is one of the most widely used computer-dosage programs. Evidence of its value and that of other computer programs has been based previously only on laboratory evidence of "time in target INR range" (TIR) not on clinical safety in practice. A five-year international randomised clinical study of computer assistance with the DAWN AC program compared with manual dosage in 2,631 patients has been performed at 13 centres with established expertise in oral anticoagulation mainly in the EU. Safety assessment have been based on the comparison of bleeding or thrombotic events with DAWN AC compared with manual dosage in a randomised study. Safety of the DAWN AC program has been demonstrated. Clinical events of bleeding and thrombosis were almost identical with the experienced manual dosage group. Therapeutic control improved with DAWN AC to 66.8% from 63.4% TIR. The program failed to provide a dosage recommendation on only 5.7% of occasions. At a group of experienced centres with a special interest in oral anticoagulation, the DAWN AC computer-dosage program proved as safe clinically as manual dosage by experienced medical staff. With DAWN AC, laboratory control was improved, the difference being highly significant. The results should reassure hospitals and community clinics that the DAWN AC program is safe and facilitate greater and longer provision of warfarin treatment where required.

Reversal agents for oral anticoagulant-associated major or life-threatening bleeding.

Oral anticoagulants (OA) are effective drugs for treating and preventing the formation of blood clots in patients with atrial fibrillation, mechanical heart valves and venous thromboembolism but their therapeutic effect is always counterbalanced by an increased risk of bleeding. Direct oral anticoagulants (DOACs) have brought advantages in the management of many patients, with evidence of a lower risk of intracranial bleeding in comparison to vitamin K antagonists (VKAs). However, due to the increased number of anticoagulated patients worldwide, major and life threatening OA-related bleeding is also increasing, and effective reversal strategies are needed. We reviewed the reversal strategies for both VKAs and DOACs in the light of the latest evidence and recent guidelines, taking into account non-specific methods with fresh frozen plasma (FFP), prothrombin complex concentrate (PCC) or four factor PCC, as well as specific reversal antidotes that are already approved or in approval phase. Most published studies on OA reversal have drawbacks, such as lacking a control arm or data on clinically relevant outcomes, and current guidelines' recommendations are mainly based on panellists' judgment. There is an urgent need for well-designed studies in this field. In the meanwhile, to improve the correct use of available resources and patients' outcomes, we suggest a seven-element bundle for an optimal management of OA-associated major bleeding, including the implementation of fast turnaround time for laboratory tests in emergency, i.e. INR and DOAC plasma levels, and to build up a 'bleeding team' that includes experts of hemostasis, lab, trauma, emergency medicine, endoscopy, radiology, and surgery in every hospital.

A multicentre randomised clinical endpoint study of PARMA 5 computer-assisted oral anticoagulant dosage.

To meet growing demand for oral anticoagulation worldwide there has been increased dependence on computer-assistance in dosage although the safety and effectiveness of any of the individual computer-assisted dosage programs has not previously been established. This randomised multicentre clinical end-point study assessed a new version of the PARMA 5 program. It compared PARMA 5 safety and effectiveness with manual dosage by experienced medical staff at 19 centres with a known interest in oral anticoagulation. Target recruitment was 8000 patient-years, randomised to medical staff or PARMA-5 assisted dosage. Safety and effectiveness of the PARMA 5 program was compared with manual dosage. A total of 10,421 patients were recruited (15,369 patient-years) in the 5-year study. International normalised ratio (INR) tests numbered 167,791 with manual and 160,078 with PARMA 5 dosage. With parma 5 there was overall a non-significant reduction in clinical events but in the 2542 patients with deep vein thrombosis/pulmonary embolism, clinical events were significantly reduced (P = 0.005). Success in achieving 'time in target INR range' was also significantly greater with PARMA 5 compared with the dosage by experienced medical staff. This study demonstrated the safety and effectiveness of PARMA 5-assisted dosage.

Clinical characteristics and management of cancer-associated acute venous thromboembolism: findings from the MASTER Registry.

BACKGROUND: Clinical characteristics and management of acute deep vein thrombosis and pulmonary embolism (PE) have been reported to be different in patients with and without cancer. The aim of this paper was to provide information on clinical characteristics and management of acute venous thromboembolism in patients with cancer by means of a large prospective registry. DESIGN AND METHODS: MASTER is a multicenter registry of consecutively recruited patients with symptomatic, objectively confirmed, acute venous thromboembolism. Information about clinical characteristics and management was collected by an electronic data network at the time of the index event. RESULTS: A total of 2119 patients were enrolled, of whom 424 (20%) had cancer. The incidence of bilateral lower limb deep vein thrombosis was significantly higher in patients with cancer than in patients without cancer (8.5% versus 4.6%; p<0.01), as were the rates of iliocaval thrombosis (22.6% versus 14%; p<0.001), and upper limb deep vein thrombosis (9.9% versus 4.8%; p<0.001). Major bleeding (3.3% versus 1.1%; p=0.001), in-hospital treatment (73.3% versus 66.6%; p=0.02) and inferior vena cava filter implantation (7.3% versus 4.1%; p=0.005) were significantly more frequent in patients with cancer, in whom oral anticoagulants were less often used (64.2% versus 82%; p<0.0001). CONCLUSIONS: The clinical presentation of acute venous thromboembolism is different and often more extensive in cancer patients than in patients free from malignancy. Moreover, the management of the acute phase of venous thromboembolism is more problematic in cancer patients, especially because of a higher rate of major bleeding and the need for implantation of inferior vena cava filters.

Factors associated with the timing of diagnosis of venous thromboembolism: results from the MASTER registry.

INTRODUCTION: Signs and symptoms of venous thromboembolism (VTE) are non-specific and thus can make diagnosis difficult, even for an experienced clinician. We aimed to evaluate the timing of diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in Italian hospitals and to identify individual and clinical predictors of timely or delayed diagnosis. MATERIAL AND METHODS: MASTER is a multicenter prospective registry of patients with acute DVT and PE. Information on clinical presentation and diagnostic methods, temporary and permanent risk factors, were captured by an electronic data network at the time of the index event. RESULTS: Data on 2047 patients (1024 males), 1505 with DVT and 542 with PE, were analysed. Delayed diagnosis (i.e. more than 10 days from onset of symptoms) was observed in 340 (22.6%) patients with DVT and in 88 (16.2%) with PE, respectively. In DVT patients, factors associated with earlier diagnosis were the presence of multiple signs or symptoms (p=0.014), the presence of pain (p=0.049), and previous venous thrombosis (p=0.016). Neither the presence of other known risk factors nor ongoing prophylaxis influenced the timing of diagnosis. In PE patients, only multiple signs or symptoms at presentation (p=0.014) and the presence of transient risk factors (p=0.001) were significantly associated with earlier diagnosis. CONCLUSIONS: Substantial delays occur when diagnosing both DVT and PE. The severity of presentation, but not patient risk profile are associated with earlier diagnosis, even in patients with signs or symptoms of PE.

The MASTER registry on venous thromboembolism: description of the study cohort.

INTRODUCTION: Information on the epidemiology and long-term clinical outcome of venous thromboembolism (VTE) is mainly based on data from clinical trials and thus may be not representative of the full spectrum of VTE patients. The aim of this multicenter registry (MASTER) was to prospectively collect data on the epidemiology and long-term clinical outcome of VTE in an unselected cohort of patients. MATERIALS AND METHODS: In symptomatic patients with objectively confirmed acute VTE, information about clinical presentation, diagnostic methods, temporary and permanent risk factors, pre-event prophylaxis and treatment were captured by an electronic data network at the time of the index event. A 24-month follow-up is currently ongoing. RESULTS: From January 2002 to October 2004, 2119 patients were included in the MASTER registry in 25 Italian centers. At entry, the mean patient age was 59.3+/-18.1 years (range 18-99 years). 1541 patients (72.7%) were affected by deep vein thrombosis, 206 patients (9.7%) by pulmonary embolism and 372 patients (17.5%) by both deep vein thrombosis and pulmonary embolism. 676 patients (31.9%) received home-treatment. 899 patients (42.4%) had one or more temporary risk factors. 381 patients (18.0%) had a known cancer at the time of the index event and in 50 patients (2.4%) a new cancer was discovered at the time of the index event. 311 patients (14.7%) had a previous VTE. CONCLUSIONS: Following a real world approach, our registry describes the clinical presentation, risk factors, diagnosis and treatment procedures in a large cohort of unselected patients with VTE.

Risk factors for venous thromboembolism in the elderly: results of the master registry.

Approximately 50-75% of patients with venous thromboembolism have a readily identifiable risk factor, either transient or permanent, whereas the remaining episodes are classified as unprovoked. The incidence of first-time venous thromboembolism rises exponentially with age. Whether the prevalence and the relative weight of major risk factors differ between elderly and younger patients is unclear. We performed a multicenter, prospective, observational study on consecutive patients with objectively confirmed acute venous thromboembolism admitted to 25 Italian hospitals. Baseline characteristics and information on temporary and permanent risk factors at the time of the index event were secured by an electronic data network. We enrolled 2119 patients (49.8% men), of whom 440 (20%) were more than 75 years of age and 1679 (79.2%) 75 years of age or less. Elderly patients were more likely to have pulmonary embolism at presentation (33.6 and 25.6%, respectively, P < 0.001). After binary logistic regression analysis, we found that the risk of venous thromboembolism in the elderly, compared with the younger age group, was significantly associated with immobilization (odds ratio: 2.46, 95% confidence interval: 1.85-3.27) and with severe medical disorders (odds ratio: 1.99, 95% confidence interval: 1.41-2.80), whereas male sex (odds ratio: 0.53, 95% confidence interval: 0.42-0.66), surgery (odds ratio: 0.61, 95% confidence interval: 0.43-0.85), and trauma (odds ratio: 0.49, 95% confidence interval: 0.31-0.77) were less common risk factors in the elderly than in younger patients. Use of thromboprophylaxis prior to the index event was not different between the two age groups. Severe medical disorders and immobilization are strongly associated with the occurrence of venous thromboembolism in the elderly. Our findings stress the need for adequate thromboprophylaxis in this setting.

How and when to measure anticoagulant effects of direct oral anticoagulants? Practical issues.

Direct oral anticoagulants (DOACs) do not require dose adjustment based on laboratory testing. However, it might be necessary to measure their plasma concentrations in the following specific situations: 1) before thrombolytic therapy in patients with stroke; 2) before surgery or invasive procedure; 3) in case of adverse events (thrombosis or hemorrhage); 4) when immediate reversal of anticoagulation is needed; 5) in patients with extreme body weight; 6) when administering additional drugs potentially interfering with DOACs; and 7) when overdosage is suspected regardless of concomitant bleeding. Basic coagulation tests, such as prothrombin and activated partial thromboplastin time, should not be used as standalone tests to assess the levels of anticoagulation as they are not specific for DOACs and their results are dependent on the type of reagent used for testing. Plasma DOAC concentrations should be assessed by dedicated tests: dilute thrombin time or ecarin tests (for dabigatran) or anti-factor Xa assays (for anti-factor Xa inhibitors). Dedicated tests should be calibrated against their respective plasma calibrators at certified DOAC concentrations and results should be expressed as ng/ml. Caution should be exerted when interpreting the results of the most common hemostatic parameters such as antithrombin, proteins C and S, lupus anticoagulant, or individual coagulation factors, as they may be strongly affected by the presence of a DOAC. Whenever possible, these parameters should be measured 4 to 5 days after discontinuation of DOAC anticoagulation.

Correction: Anticoagulation Knowledge Tool (AKT): Further evidence of validity in the Italian population.

[This corrects the article DOI: 10.1371/journal.pone.0201476.].

Anticoagulation Knowledge Tool (AKT): Further evidence of validity in the Italian population.

INTRODUCTION: Oral Anticoagulation therapy (OAC) is highly effective in the management of thromboembolic disorders. An adequate level of knowledge is important for self-management and optimizing clinical outcomes. The Anticoagulation Knowledge Tool (AKT) was developed to assess OAC knowledge and caters for both patients prescribed direct oral anticoagulants or vitamin K antagonist (VKA). However, evidence regarding its psychometric proprieties, validity and reliability are unavailable in non-English speaking settings. For this reason, the aim of this study is to provide further evidence of validity for AKT and also developing an Italian AKT version (I-AKT) supported by evidence of validity and reliability. METHODS: A multiphase study was conducted which included the following: cultural and linguistic validity; i.e. content validity; construct validity; reliability assessment. The Construct validity was performed using the contrasted group approach using three groups comprised of health care providers, patients and the general public. Furthermore, Exploratory Structural Equation Modelling (ESEM) was performed to confirm the mono-dimensional structure of the items in the AKT. RESULTS: In construct validity phase 334 participants were enrolled. One-way ANOVA and post hoc analysis test demonstrated significant differences between the means knowledge scores of the three groups: 30.42±3.04 vs 23.45± 4.57 vs14.32±6.07 (Statistic F = 266.83; p < .001). ESEM analysis demonstrates the I-AKT mono-dimensionally structure with an explained variance of 56.42%. The scale also showed both good internal consistency reliability (Cronbach's α = 0.896) and test-retest reliability (r = 0.855). CONCLUSION: This study developed and validated I-AKT with supporting evidence for validity and reliability. The study also confirms the mono-dimensional of the items in the AKT. This suggest that the instrument can be useful in non-English setting for knowledge assessment and in potentially developing patient education materials.