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Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer.

Purpose: The increasing use of direct oral anticoagulants (DOACs) in patients undergoing oral surgery highlights the need for well-defined, evidence-based recommendations on perioperative and postoperative bleeding management. This review aims to evaluate bleeding risks and strategies to optimize the management of patients treated with DOACs undergoing oral surgical procedures. Methods: A systematic review identified 628 articles, of which 17 met the inclusion criteria. These studies focused exclusively on patients treated with DOACs—Dabigatran, Rivaroxaban, Apixaban, and Edoxaban—undergoing oral surgical procedures, such as tooth extractions, dental implants, and soft tissue surgical procedures. Articles involving other anticoagulants or combined therapies were excluded to ensure precision in evaluating DOAC-specific outcomes. Results: The findings revealed that minor to moderate bleeding events were relatively common, while severe bleeding requiring hospitalization was rare. Bleeding events were effectively managed using standard local hemostatic measures in most cases. This review highlights the importance of scheduling procedures when DOAC levels are at their lowest, as this minimizes the risk of excessive bleeding. Furthermore, the continuation of DOAC therapy during oral surgery was deemed safe, with effective local management strategies mitigating bleeding risks. Conclusion: This review offers practical, evidence-based recommendations for the management of patients on DOAC therapy undergoing oral surgical procedures. The findings simplify clinical decision-making and improve patient safety by emphasizing the importance of timing and perioperative strategies. The exclusive focus on DOACs underscores the clinical significance of this work in guiding oral and maxillofacial surgeons. [ABSTRACT FROM AUTHOR]

Background: Swift reversal of oral anticoagulation is deemed essential for the outcome of patients with anticoagulation-related critical bleeding. The aim of this systematic review was to evaluate the benefits and harms of prothrombin complex concentrate (PCC) in patients with oral anticoagulants-related critical bleeding. Methods: For this systematic review CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Web of Science, and clinical trial registries were systematically searched. Clinical study reports were also requested from competent authorities. Eligible for inclusion were randomised clinical trials comparing PCC versus no intervention, placebo, or other reversal interventions in participants with critical bleeding related to ongoing treatment with vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC). Pre-specified primary outcomes were all-cause mortality, health-related quality of life, and serious adverse events for which meta-analyses, Trial Sequential Analysis, and GRADE assessments were conducted. Results: Three trials, randomising a total of 291 participants, evaluated PCC against two different active comparators in participants with VKA-related critical bleeding, and two trials, randomising a total of 534 participants, evaluated PCC against two different active comparators in participants with factor Xa-related critical bleeding. Among participants with VKA-related critical bleeding, meta-analyses showed no evidence of a difference between PCC versus fresh frozen plasma (FFP) when assessing all-cause mortality (risk ratio [RR] 1.05; 95% confidence interval (CI) 0.27 to 4.05; low certainty), health-related quality of life (mean difference 1.04; 95% CI − 0.94 to 3.02; very low certainty), and serious adverse events (RR 1.33; 95% CI 0.94 to 1.88; very low certainty), but information is currently sparse. Among participants with factor Xa-related critical bleeding, PCC could not be shown superior or inferior to other reversal strategies (FFP or andexanet alfa) on any patient-relevant outcome, but information is currently sparse. Conclusion: Among participants with VKA or DOAC-related critical bleeding, evidence from randomised clinical trials is currently insufficient to establish if PCC is superior or inferior versus other interventions in decreasing the risk of undesirable patient-relevant outcomes or improving health-related quality of life. [ABSTRACT FROM AUTHOR]

Background: The surgical outcomes of minimally invasive surgery (MIS) for gastrointestinal (GI) cancers in patients receiving anticoagulation therapy (ACT) are unknown. We investigated the effect of ACT on the surgical outcomes of minimally invasive major GI surgery, with a particular focus on postoperative bleeding and thromboembolic complications. Methods: A total of consecutive 1290 patients undergoing elective minimally invasive (laparoscopic and robotic) major GI surgery (esophagogastric and colorectal resection for malignancy) between 2014 and 2023 were enrolled. The patients were divided into three groups: patients without receiving anticoagulation therapy (non-ACT, n = 1076), patients receiving direct oral anticoagulants (DOAC, n = 144), and patients receiving warfarin (WF, n = 70). Outcome variables were compared between the groups and the risk factors of postoperative bleeding complications were assessed using logistic multivariate analysis. Results: The overall rate of thromboembolic complication was 0.5%, and the operative mortality was zero in the whole cohort. The incidences of postoperative bleeding in the non-ACT, DOAC, and WF groups were 1.0%, 6.9% and 11.4%, respectively (P < 0.001). Among 8 DOAC-received patients with postoperative GI bleeding, 75% of cases occurred on postoperative day 5 or later. Multivariate analysis showed DOAC (odds ratio = 5.420, P < 0.001) and perioperative heparinization (odds ratio = 3.770, P = 0.048) were significant risk factors for major postoperative bleeding. Conclusions: Although minimally invasive major GI surgery can be safely performed in patients receiving ACT, attention should be paid for the occurrence of delayed GI bleeding especially in the DOAC-received patients. Patients treated with DOAC or perioperative heparinization still represent a challenging group in the present cohort, and need to be carefully managed. [ABSTRACT FROM AUTHOR]

Background and aim: Some patients with intracerebral hemorrhage are on antithrombotic agents at the time of the event and these may worsen outcome, but the relative risk of different oral anticoagulants and antiplatelet agents is uncertain. We determined associations between pre-onset intake of antithrombotic agents and initial stroke severity, and outcomes, in patients with intracerebral hemorrhage. Methods: Patients with intracerebral hemorrhage admitted within 24 h after onset between January 2017 and December 2020 and recruited to the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, were included. Enrolled patients were classified into four groups based on the type of antithrombotic agents being used on admission. The outcomes were the National Institutes of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale (mRS) of 5–6 at discharge. Results: Of a total 9810 patients with intracerebral hemorrhage (4267 females; mean age = 70 ± 15 years), 77.1% were classified into the no-antithrombotic group, 13.2% into the antiplatelet group, 4.0% into the warfarin group, and 5.8% into the direct oral anticoagulant (DOAC) group. Median (interquartile range) NIHSS score on admission was 12 (5–22), 13 (5–26), 15 (5–30), and 13 (6–24), respectively, in the four groups. In multivariable analysis, the prestroke warfarin use was associated with higher NIHSS score (adjusted incidence rate ratio = 1.09 (95% confidence interval (CI) = 1.06–1.13), with the no-antithrombotic group as the reference), but the antiplatelet group (1.00 (95% CI = 0.98–1.02)) and DOAC group (0.98 (95% CI = 0.95–1.01)) were not. The rate of mRS 5–6 at discharge was 30.8%, 41.9%, 48.6%, and 41.5%, respectively, in the four groups. In multivariable analysis, prestroke warfarin use was associated with mRS 5–6 (adjusted odds ratio = 1.90 (95% CI = 1.28–2.81), with the no-antithrombotic group as the reference), but the antiplatelet group (1.12 (95% CI = 0.91–1.37)) and DOAC group (1.25 (95% CI = 0.88–1.77)) were not. Conclusion: Patients who were taking warfarin prior to intracerebral hemorrhage onset suffered more severe intracerebral hemorrhage as evidenced by higher admission NIHSS and higher discharge mRS. In contrast, no increase in severity was seen with antiplatelet agents. [ABSTRACT FROM AUTHOR]

Objectives: Evidences for anticoagulation strategies in cirrhotic with portal vein thrombosis (PVT) are still insufficient. This study aims to comprehensively compare the therapeutic effects of different therapeutic therapeutic measures in individuals suffering from cirrhosis with PVT, with the ultimate goal of providing evidence-based recommendations for thrombolytic therapy in this population. Methods: Starting from 20 October 2023, a comprehensive search about therapeutic strategies for portal vein thrombosis in cirrhosis was conducted on PubMed, EMBASE, and Cochrane Library. Results: 19 studies were eventually incorporated into this study. Comparison with control in network meta-analysis, direct oral anticoagulants (DOACs) (RR = 2.15, 95%CI: 1.33, 3.48), LMWH (RR = 1.41, 95%CI: 1.01, 1.99), TIPS (RR = 5.68, 95%CI: 2.63, 12.24), warfarin (RR = 2.16, 95%CI: 1.46, 3.21), EBL plus propranolol (RR = 2.80, 95%CI: 1.18, 6.60), LMWH-DOACs sequential (RR = 7.92, 95%CI: 2.85, 21.99) and LMWH-warfarin sequential (RR = 2.26, 95%CI: 1.16, 4.42) significantly improved the incidence of complete recanalization. The anticoagulation drugs were ranked based on their SUCRA values, with the LMWH-DOACs sequential (92.7%), TIPS plus warfarin (91.3%), and TIPS (80.3%) emerging as the top three effective treatments. Conclusion: In this study, active anticoagulants were recommended for cirrhosis with PVT. The TIPS plus warfarin, LMWH-DOACs sequential, and TIPS improved the complete recanalization rate most effectively, and the EBL plus propranolol, heparin plus DOACs plus warfarin, and DOACs were highly recommended for increasing the incidence of partial recanalization. Warfarin and TIPS were recommended for reducing the frequency of bleeding events, while LMWH plus warfarin and DOACs proved to be most effective in decreasing the rate of major bleeding events. Warfarin, heparin plus DOACs plus warfarin, and DOACs demonstrated the most significant reduction in mortality rates, highlighting its potential as an effective intervention. TIPS plus warfarin, LMWH-DOACs sequential, and TIPS were recommended for reducing the occurrence of PVT expansion. Heparin plus DOACs plus warfarin was recommended for reducing the occurrence of hepatic encephalopathy, and protocols that involve TIPS were generally associated with a higher risk of hepatic encephalopathy. However, a longer follow-up period is necessary to comprehensively evaluate the efficacy of active anticoagulants therapy in patients with PVT in cirrhosis. [ABSTRACT FROM AUTHOR]

Introduction: Inappropriate use of direct oral anticoagulants (DOACs) is common, affecting up to 30% of atrial fibrillation (AF) population receiving treatment for stroke prevention. This study assessed appropriateness of anticoagulation in anticoagulation-naive AF patients treated with DOACs during a 12-month prospective follow-up. Methods: This prospective cohort study included all anticoagulation-naive AF patients referred for anticoagulation for stroke prevention at a tertiary cardiovascular center. Participants were prospectively followed through phone call interviews by a dedicated nurse at 1, 3, 6, 9, and 12 months after enrollment. Results: Of 403 anticoagulation-naive AF patients, rivaroxaban was prescribed for 325 patients (80.7%) and apixaban for 78 (19.3%). Inappropriate therapy was observed in 23% (76/325) and 46% (36/78) of patients treated with rivaroxaban and apixaban, respectively. Undertreatment was predominant scenario for both drugs, detected in 78.5% (78/112) of patients treated inappropriately, and was more frequently observed with apixaban versus rivaroxaban (44.8% vs 16.3%). During 12 months, inappropriate treatment was corrected in only 13% of all patients. The multivariate regression model identified creatinine clearance ≤ 49 mL/min (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.12 to 4.21), female sex (OR, 1.81; 95% CI, 1.11 to 2.97), and age ≥ 80 years (OR, 1.85; 95% CI, 1.22 to 2.83) as independent covariates associated with inappropriate dosing. Conclusions: Inappropriate therapy with DOACs for stroke prevention in patients with AF is common, and the dosage were corrected in few patients during the 12-month follow-up. Our findings highlight the persistent lack of knowledge regarding appropriate DOAC dosage and need for continuous education. [ABSTRACT FROM AUTHOR]

Aims: Computerized decision support systems (CDSSs) aim to prevent adverse drug events. However, these systems generate an overload of alerts that are not always clinically relevant. Anticoagulants are frequently involved in these alerts. The aim of this study was to investigate the efficiency of CDSS alerts on anticoagulants in Dutch hospital pharmacies. Methods: A multicentre, single‐day, cross‐sectional study was conducted using a flashmob design in Dutch hospital pharmacies, which have CDSSs that operate on both a national medication surveillance database and on self‐developed clinical rules. Hospital pharmacists and pharmacy technicians collected data on the number and type of alerts and time needed for assessing these alerts. The primary outcome was the CDSS efficiency on anticoagulants, defined as the percentage of alerts on anticoagulants that led to an intervention. Secondary outcomes where among other CDSSs efficiency related to any medications and the time expenditure. Descriptive data‐analysis was used. Results: Of the 69 hospital pharmacies invited, 42 (61%) participated. The efficiency of CDSS alerts on anticoagulants was 4.0% (interquartile range [IQR] 14.0%) for the national medication surveillance database alerts and 14.3% (IQR 40.0%) for alerts from clinical rules. For any medication, the efficiency was lower: 1.8% (IQR 7.5%) and 13.4% (IQR 21.5%) respectively. The median time for assessing the relevance of all alerts was 2 (IQR 1:21) h/day for pharmacists and 6 (IQR 5:01) h/day for pharmacy technicians. Conclusion: CDSS efficiency is generally low, both for anticoagulants and any medication, while the time investment is high. Optimization of CDSSs is needed. [ABSTRACT FROM AUTHOR]

Purpose: The outcomes of direct oral anticoagulant use after noncardiac thoracic surgery have not been elucidated. We compared the safety and efficacy of the postoperative use of direct oral anticoagulants versus warfarin. Methods: This retrospective cohort study included patients taking anticoagulants after noncardiac thoracic surgery between 2008 and 2021. Patients were divided into 2 groups based on drug type: Group D (direct oral anticoagulants) and Group W (warfarin). The occurrence of bleeding and thromboembolic events was also assessed. Results: Anticoagulants were administered to 434 postoperative patients. One (0.4%) of the 247 patients in Group D and 3 (1.6%) of the 187 patients in Group W experienced thromboembolic events. Four patients (1.6%) in Group D and 4 (2.1%) patients in Group W experienced bleeding events. All bleeding events in Group D occurred within 1 week of oral administration, whereas only 1 case of bleeding occurred after resumption in Group W. Conclusions: The outcomes of patients treated with direct oral anticoagulants did not differ from those of patients treated with warfarin. However, major bleeding can occur after the postoperative resumption of direct oral anticoagulant use. Attention should be paid to resuming oral anticoagulants within a few days of non-cardiac thoracic surgery. [ABSTRACT FROM AUTHOR]

The main objective of this study was to investigate the optimal post-left atrial appendage closure (LAAC) anticoagulation strategy, focusing on minimizing device-related thrombosis (DRT) and thromboembolism (TE) events without increasing bleeding risk. After successful LAAC, consecutive participants were treated with 45-day anticoagulants (rivaroxaban 15 mg daily, dabigatran 110 mg twice a day, and warfarin). The efficacy endpoints included DRT, TE, and hospital readmissions due to cardiac caused, while safety endpoints encompassed bleeding events, monitored over a 12-month follow-up period. The incidence of DRT was relatively lower in the rivaroxaban group compared to both the dabigatran and warfarin groups (rivaroxaban vs. dabigatran: HR = 0.504, 95% CI 0.208–1.223, log-rank P = 0.101; rivaroxaban vs. warfarin: HR = 0.468, 95% CI 0.167–1.316, log-rank P = 0.093). The median [interquartile range] length and width of DRT in the rivaroxaban group were 1.92 [1.68–2.15] mm and 1.49 [1.28–1.76] mm, both significantly lower than those in the dabigatran (length = 2.15 [1.99–2.25] mm, P = 0.036; width = 1.60 [1.54–1.85] mm, P = 0.035) and warfarin groups (length = 2.26 [2.11–2.44] mm, P = 0.006; width = 1.74 [1.54–1.85] mm, P = 0.006). Kaplan-Meier survival analysis indicated that procedural bleeding was more common in the warfarin group. The 12-month incidence of TE was significantly lower in the rivaroxaban group compared to the dabigatran (HR = 0.466, 95% CI 0.221–0.984, log-rank P = 0.029) and warfarin groups (HR = 0.456, 95% CI 0.188–0.966, log-rank P = 0.042). Long-term antithrombotic therapy with reduced dose of rivaroxaban significantly reduced the risk of DRT and composite endpoints without increasing bleeding events, compared to warfarin and dabigatran, for patients following LAAC. [ABSTRACT FROM AUTHOR]

Abstract Background Swift reversal of oral anticoagulation is deemed essential for the outcome of patients with anticoagulation-related critical bleeding. The aim of this systematic review was to evaluate the benefits and harms of prothrombin complex concentrate (PCC) in patients with oral anticoagulants-related critical bleeding. Methods For this systematic review CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Web of Science, and clinical trial registries were systematically searched. Clinical study reports were also requested from competent authorities. Eligible for inclusion were randomised clinical trials comparing PCC versus no intervention, placebo, or other reversal interventions in participants with critical bleeding related to ongoing treatment with vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC). Pre-specified primary outcomes were all-cause mortality, health-related quality of life, and serious adverse events for which meta-analyses, Trial Sequential Analysis, and GRADE assessments were conducted. Results Three trials, randomising a total of 291 participants, evaluated PCC against two different active comparators in participants with VKA-related critical bleeding, and two trials, randomising a total of 534 participants, evaluated PCC against two different active comparators in participants with factor Xa-related critical bleeding. Among participants with VKA-related critical bleeding, meta-analyses showed no evidence of a difference between PCC versus fresh frozen plasma (FFP) when assessing all-cause mortality (risk ratio [RR] 1.05; 95% confidence interval (CI) 0.27 to 4.05; low certainty), health-related quality of life (mean difference 1.04; 95% CI − 0.94 to 3.02; very low certainty), and serious adverse events (RR 1.33; 95% CI 0.94 to 1.88; very low certainty), but information is currently sparse. Among participants with factor Xa-related critical bleeding, PCC could not be shown superior or inferior to other reversal strategies (FFP or andexanet alfa) on any patient-relevant outcome, but information is currently sparse. Conclusion Among participants with VKA or DOAC-related critical bleeding, evidence from randomised clinical trials is currently insufficient to establish if PCC is superior or inferior versus other interventions in decreasing the risk of undesirable patient-relevant outcomes or improving health-related quality of life.

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.

Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.

Aim. To analyze published clinical trials to evaluate the safety and effectiveness of direct oral anticoagulants in comparison with warfarin in a population of patients with atrial fibrillation and chronic kidney disease stages C4-C5.Material and methods. The meta-analysis was conducted in accordance with PRISMA guidelines based on a literature search in the PubMed/MEDLINE database for the period from 01 January 2018 to 25 December 2023. Keywords included the MeSH terms "atrial fibrillation" and "dialysis" or "hemodialysis" or "end-stage kidney disease" or "end-stage renal disease" or "advanced renal disease" or "stage 4 or 5 chronic kidney disease" or "stage 5 chronic kidney disease" and "non-vitamin K antagonist oral anticoagulants" or "direct oral anticoagulants" or "novel oral anticoagulant" or "NOAC" or "DOAC" or "dabigatran" or "apixaban" or "rivaroxaban" and "vitamin K antagonist" or "warfarin" and "outcomes". ROBINS-I and RoB2 tools were used to assess the systematic error of the research.Results. When searching the literature based on the chosen strategy, 1,895 publications were selected, some of which were excluded due to inconsistency with the inclusion criteria; as a result, 13 studies that did not have exclusion criteria were included in the analysis. The meta-analysis included 60,109 patients from 13 studies, 9,991 of whom received direct oral anticoagulants and 50,118 received warfarin. The results showed that in patients with stage C4-C5 chronic kidney disease treated with direct oral anticoagulants, ischemic stroke/systemic embolism was 26% less likely to develop compared with warfarin (HR=0.74, 95% CI 0.57–0 .95, p=0.02). The pooled effect of direct oral anticoagulant treatment demonstrated a lower risk of major bleeding (HR=0.74, 95% CI 0.67–0.82, p

Abstract This study reveals one-step green synthesis of plant inspired silver nanoparticles (Ag-NPs). The synthesis procedure relies on the bio-reduction of Ag+ to Ag0 using orange waste (orange peel) extract as cheap, readily available, sustainable, biocompatible feedstocks as a reducing and stabilizing agent. The prepared Ag-NPs passed through a full characterization procedure for better confirmation and elucidation of optical and structural properties. The fluorescence of the prepared Ag-NPs has a quantum yield of 17.15% enabling its potential use in chemical sensing of drugs. Ag-NPs are conceived to be used as a fluorescent nano sensor for sensitive, ecofriendly, rapid spectrofluorimetric determination of two recent direct oral anticoagulants, namely, rivaroxaban (RIV) and edoxaban tosylate monohydrate (EDT); COVID-19 adjunctive drugs in their raw materials and pharmaceutical tablets. The fluorescence of the prepared Ag-NPs at 333 nm $${(\uplambda }_{\text{ex}}=258 \text{nm})$$ ( λ ex = 258 nm ) was found to be substantially quenched in existence of increasing concentrations of each drug. The quenching mechanisms were studied and explained. The validation of the method revealed linear correlation over the ranges of 0.5–10 µg/ml with an excellent regression correlation (r = 0.9999) for both drugs with minimum detection limits of 0.14 and 0.16 µg/ml for rivaroxaban and edoxaban tosylate monohydrate, correspondingly. Three different metrics were employed for verifying the greenness profile of the presented study. The findings of the greenness assessment were congruent and compatible with the green synthesis procedure, ecofriendly analysis, and the exclusion of using organic solvents and noxious materials opening an avenue for green synthesis of nanoparticles instead of chemical and physical methods.

The Beers Criteria are a tool for optimizing pharmacotherapy in elderly patients, containing information on potentially inappropriate drugs, which is only advisory in nature and is not mandatory for use in Russian Federation. In the updated version of the Beers Criteria from 2023, the expert opinion on rivaroxaban has changed — instead of "use with caution", as stated in the previous document from 2019, the experts now believe that "long-term treatment with rivaroxaban in non-valvular atrial fibrillation (AF) and venous thromboembolic complications (VTE) should be avoided in favor of safer alternative anticoagulants". This statement is based on moderate-quality evidence obtained from observational studies and network meta-analyses, which are significantly inferior to randomized controlled trials and have numerous limitations. The available evidence base for the use of rivaroxaban in elderly patients with AF and VTE and critical comments on the Beers criteria methodology, indicate the recommendations of the American Geriatrics Society experts regarding direct oral anticoagulants (DOAC) should be treated thoughtfully and carefully. When choosing a DOAC in elderly patients with AF or VTE, one should primarily focus on current clinical guidelines mandatory for use in Russian Federation, and on the data of studies that studied the efficacy and safety of specific DOACs in this category of patients. Rivaroxaban is a well-studied anticoagulant in elderly patients with AF and VTE, since its efficacy and safety have been established in RCTs and specially designed multicenter prospective observational studies with a fairly high quality of evidence. Based on this, rivaroxaban is a justified treatment option for elderly and senile patients with AF or VTE.

ABSTRACT Aims Methods Results Conclusions Budd‐Chiari syndrome (BCS) is managed by interventions aimed at relieving hepatic venous obstruction and anticoagulation. Despite robust data supporting the tolerability and efficacy of direct oral anticoagulants (DOACs) in patients with other venous thromboembolism, its utility in BCS is not well documented. This study aims to evaluate the efficacy and tolerability of DOACs in Primary BCS from the available literature.Published studies that reported data on patients with BCS treated with DOACs were included.Two retrospective studies and nine case reports met the criteria for inclusion. The combined data from these two retrospective studies include 58 patients administered DOAC and 101 patients treated with VKA/LMWH. The combined re‐stenosis or failure rates after percutaneous endovascular intervention, angioplasty, TIPS, or OLT were 17.2% for the DOAC group and 15.8% for the LMWH/VKA group. The incidence of major bleeding was 8.62% in the DOAC group and 5.94% in the LMWH/VKA group, while minor bleeding rates were 20.7% and 4.95%, respectively. Procedure‐related bleeding was 4.5% in DOAC group and 12.8% in VKA/LMWH group. Nine case reports using apixaban in 3, rivaroxaban in 5, and one with dabigatran‐ described patients tolerating the treatment well and experiencing no major adverse events.DOACs appear to be at least equally effective to LMWH/VKA for the anticoagulation of patients with BCS. We believe DOACs to be preferred over LMWH/VKA for the anticoagulation of patients with BCS due to the known advantages in administration, but randomized trials might be needed to answer this question. [ABSTRACT FROM AUTHOR]

Background: Managing cancer-associated thrombosis (CAT) is a significant clinical challenge due to several factors such as increased bleeding tendency, frailty, and drug-drug interactions. For many years, the drug of choice for treating CAT was low molecular weight heparin (LMWH). Recently, direct oral anticoagulants (DOACs) entered to the therapeutic milieu of CAT. However, due to the large diversity among patients with CAT in clinical and laboratory characteristics, not all patients will equally benefit from treatment with DOACs. Furthermore, several subgroups of patients with CAT have specific characteristics that influence the anticoagulant decision-making process. Summary: In this review, we present four different theoretical clinical case scenarios, each representing a different challenge that is associated with thrombosis management; brain metastasis, malignancies of the gastrointestinal tract, drug-drug interactions (DDIs), and thrombocytopenia. By reviewing current literature, we suggest our clinical approach for managing these cases in the era of DOACs. Key Messages: (1) The management of patients with brain tumors and CAT is challenging due to increased risk for both intracranial hemorrhage and recurrent venous thromboembolism. Both LMWH and DOACs are optional treatment in this setting. (2) There are conflicting data regarding the bleeding risk in patients with GI malignancies. Treatment with LMWH should be considered specifically in patients with advanced disease and unresectable tumors. (3) There is a paucity of data regarding DDI in patients with CAT. However, caution should be exercised when prescribing DOACs to patients receiving concurrent medications that either affect DOAC metabolism or influence bleeding risk. (4) The management of patients with CAT and thrombocytopenia depends on the severity of thrombocytopenia and the timing of the thrombotic event. [ABSTRACT FROM AUTHOR]

Background: As direct oral anticoagulants (DOACs) have become widely recommended as first-line anticoagulation therapy, patients who remain on warfarin are likely those unable to afford, adhere to, or utilize DOAC therapy due to the presence of a contraindication. It is currently unknown how availability of DOACs have affected populations being managed at warfarin (VKA) anticoagulation clinics. Methods: This was a retrospective chart review assessing warfarin-treated patients at an outpatient anticoagulation clinic. The primary endpoint was the 6-month time in therapeutic range (TTR) before and after DOACs were recommended as first-line therapy by clinical guidelines. Study periods were January to June 2015, before DOACs were recommended over VKA, and January to June 2022, when DOACs were often recommended over VKA. TTR, demographic changes, and the presence of contraindications to DOAC therapy in the clinic population between the two time periods were assessed. Results: No difference in 6-month TTR was observed between study periods (59% in 2015 vs 63% in 2022; P =.45). Patient demographics did not significantly vary, which may be due to the clinic retaining 45% of patients between both time periods. Contraindications to DOAC therapy were identified in 39% of the 2015 group and 49% of the 2022 group (P =.18). The most common contraindication was indication for anticoagulation. Conclusion: Availability of DOACs did not seem to significantly affect the population or management of warfarin-treated patients at an outpatient anticoagulation clinic, however, contraindications and potential challenges to use of DOAC therapy are present in many patients. [ABSTRACT FROM AUTHOR]

Background and Aim: The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method. Methods: This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs. Results: Among the 62 eligible patients, 53 (85%) were male (median age, 76 years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P < 0.01) and continuation of antiplatelet therapy (P = 0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported. Conclusions: Continuous warfarin therapy is preferred. DOAC withdrawal 1 day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge. [ABSTRACT FROM AUTHOR]

This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible. Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; I2 = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, I2 = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, I2 = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, I2 = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, I2 = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, I2 = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, I2 = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes. Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results. [ABSTRACT FROM AUTHOR]

This article aims to discuss the literature on switching to an anticoagulant with a different mechanism of action in case of treatment failure. We present a patient with atrial fibrillation who incurred an embolic stroke despite adequate anticoagulation with apixaban and developed a new symptomatic ischemic stroke during the same admission after switching to rivaroxaban, a factor Xa inhibitor with a similar mechanism of action. He had no new events at 3‐months after switching to dabigatran, a direct thrombin inhibitor. We identified no apparent reason for anticoagulation failure in our patient. The literature on switching anticoagulants in case of failure is inconclusive with no strong supportive evidence. More research is needed to define anticoagulation failure and identify cases with factor Xa inhibitor resistance, in which switching to a different mechanism of anticoagulation may be appropriate. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess if dicloxacillin/flucloxacillin reduces the therapeutic efficacy of direct oral anticoagulants (DOACs) and the underlying molecular mechanism. Methods: In a randomized, crossover study, we assessed whether dicloxacillin reduces oral absorption of drugs through P‐glycoprotein (P‐gp) during 10 and 28 days of treatment. To study the impact of dicloxacillin/flucloxacillin on intestinal and hepatic expression of P‐gp in vitro, we usd LS174T cells and 3D spheroids of primary human hepatocytes. Finally, we used nationwide Danish health registries and the UK's Clinical Practice Research Datalink to estimate hazard ratios (HRs) for the risk of stroke and systemic embolism following dicloxacillin/flucloxacillin exposure among DOAC users, using phenoxymethylpenicillin and amoxicillin as active comparators. Results: Dicloxacillin reduced the area under the curve of dabigatran to a geometric mean ratio 10 days of 0.67 (95% confidence interval [CI]: 0.42–1.1) and geometric mean ratio 28 days of 0.72 (95% CI: 0.39–1.4), suggesting reduced oral absorption via increased P‐gp expression. In vitro, dicloxacillin raised P‐gp expression in both intestinal and liver cells, while flucloxacillin only affected liver cells. In the pharmacoepidemiologic study, dicloxacillin and flucloxacillin were not associated with increased risk of stroke/systemic embolism (dicloxacillin vs. phenoxymethylpenicillin HR: 0.93, 95% CI: 0.72–1.2; flucloxacillin vs. amoxicillin HR: 0.89, 95% CI: 0.51–1.5). Conclusions: Dicloxacillin increases expression of intestinal P‐gp, leading to reduced oral absorption of dabigatran. However, concomitant use of dicloxacillin/flucloxacillin was not associated with stroke and systemic embolism among DOAC users, suggesting no clinical impact from the drug–drug interaction between dicloxacillin/flucloxacillin and DOACs. [ABSTRACT FROM AUTHOR]

This study reveals one-step green synthesis of plant inspired silver nanoparticles (Ag-NPs). The synthesis procedure relies on the bio-reduction of Ag+ to Ag0 using orange waste (orange peel) extract as cheap, readily available, sustainable, biocompatible feedstocks as a reducing and stabilizing agent. The prepared Ag-NPs passed through a full characterization procedure for better confirmation and elucidation of optical and structural properties. The fluorescence of the prepared Ag-NPs has a quantum yield of 17.15% enabling its potential use in chemical sensing of drugs. Ag-NPs are conceived to be used as a fluorescent nano sensor for sensitive, ecofriendly, rapid spectrofluorimetric determination of two recent direct oral anticoagulants, namely, rivaroxaban (RIV) and edoxaban tosylate monohydrate (EDT); COVID-19 adjunctive drugs in their raw materials and pharmaceutical tablets. The fluorescence of the prepared Ag-NPs at 333 nm (λ ex = 258 nm) was found to be substantially quenched in existence of increasing concentrations of each drug. The quenching mechanisms were studied and explained. The validation of the method revealed linear correlation over the ranges of 0.5–10 µg/ml with an excellent regression correlation (r = 0.9999) for both drugs with minimum detection limits of 0.14 and 0.16 µg/ml for rivaroxaban and edoxaban tosylate monohydrate, correspondingly. Three different metrics were employed for verifying the greenness profile of the presented study. The findings of the greenness assessment were congruent and compatible with the green synthesis procedure, ecofriendly analysis, and the exclusion of using organic solvents and noxious materials opening an avenue for green synthesis of nanoparticles instead of chemical and physical methods. [ABSTRACT FROM AUTHOR]

Due to their widespread use, testing for direct oral anticoagulants (DOACs) has become urgent in certain clinical situations. Screening based on widely available, rapid, and simple hemostasis assays such as prothrombin time, activated partial thromboplastin time, or even diluted Russel Viper venom time may provide sufficient evidence of "over-coagulation" and could be used "in small/peripheral/spoke laboratories" as an emergency strategy, but is not thought to be reliable for driving clinical decision making. Given their good correlation with plasma concentration, urine dipsticks may be considered a valuable alternative for emergency screening, although their performance is dependent on renal function, may vary depending on the time since the last urination, and there may be problems of interfacing with the laboratory/hospital information system. Separation methods based on liquid chromatography and mass spectrometry may be clinically questionable, since they measure the concentration rather than the actual inhibitory effect of DOACs, are relatively expensive, cumbersome and time consuming, and therefore seem unsuitable for most conditions requiring urgent clinical decision making. A proposed approach therefore involves establishing a network of routine clinical laboratories, designating a reference center where DOAC tests could be available 24/7, establishing a clear diagnostic care pathway for ordering the tests from the laboratory and standard operating procedures for performing them, the use of the diluted thrombin time for dabigatran and anti-FXa assays (drug-calibrated) for rivaroxaban, apixaban, and edoxaban, as well as providing expert advice throughout the testing process, from ordering to interpretation of results. [ABSTRACT FROM AUTHOR]

The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection. [ABSTRACT FROM AUTHOR]

Background and objective: Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China. Methods: A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses. Results: Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase. Conclusion: Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer. [ABSTRACT FROM AUTHOR]

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included. [ABSTRACT FROM AUTHOR]

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Background and Objectives: Direct oral anticoagulants (DOACs) have become the cornerstone of stroke prevention in the management of atrial fibrillation (AF). While their efficacy in preventing catastrophic outcomes is well documented, the exploration of their effects on haematological parameters, particularly in clinically stable AF patients, remains markedly underrepresented in existing research. The aim of our investigation was to delineate the variations in key haematological parameters, with a special focus on haemoglobin (Hb), in a cohort of clinically stable patients afflicted with AF and receiving diverse oral anticoagulant treatments. Materials and Methods: In this retrospective study, 742 patients with AF were evaluated. Following exclusion criteria, 530 patients were included and categorised based on the change in their Hb levels (ΔHb < 2 [n = 473] vs. ΔHb ≥ 2 [n = 57]) after one year of initial prescription of DOACs. Results: Patients in the ΔHb ≥ 2 g/dL group demonstrated significantly higher baseline haemoglobin levels during the pre-DOAC period (13.5 [12.3–14.6] vs. 14.6 [13.1–15.7]; p = 0.002). Baseline haemoglobin was identified as a predictive factor for a decrease in Hb ≥ 2 g/dL, with higher initial values being associated with more pronounced reductions (OR, 95% CI: 1.424 [1.178–1.723]; p < 0.005). This pattern was observed consistently across various types and dosages of DOACs. Conclusions: This study underscores the importance of vigilant clinical monitoring for anaemia in patients undergoing DOAC therapy, even when their clinical course appears to be stable. [ABSTRACT FROM AUTHOR]

Introduction: Oral anticoagulant drugs reduce the risk of stroke associated with atrial fibrillation. Vitamin K antagonists, gold standard therapy for decades, have been deposed by the direct oral anticoagulants that exhibit superior safety profiles. However, hemorrhagic complications remain a major concern to anticoagulation. Areas covered: We searched available data in the literature to review the current knowledge on the safety profiles of available anticoagulants Expert opinion: Despite a relevant leap forward with the introduction of DOACs, safety concerns persist in some fields of the current pharmacotherapy for stroke prevention in atrial fibrillation. In-depth knowledge of the safety profile of available anticoagulants and dealing with safety issues in patient subgroups is of utmost importance. Bleeding risk scores should not be dichotomously used to decide anticoagulation treatment but rather to promote shared decision, identify and correct modifiable risk factors, and set monitoring frequency. Additional issues that wait to be investigated in order to improve the safety of therapy include circulating levels of direct oral anticoagulants and anticoagulation in patient sub-groups: very elderly, frail, those with advanced kidney or liver disease, and so on. Safety may be improved from the in-depth knowledge of safety concerns and therapeutic options. [ABSTRACT FROM AUTHOR]