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BACKGROUND: The risk of intracranial bleeding during anticoagulation for venous thromboembolism (VTE) is substantial and persists beyond the initial treatment phase. We aimed to refine risk-assessment through phase-specific prognostic scores. METHODS: We identified data from 77,786 VTE patients in the RIETE registry from March 2009 to October 2023 to develop two prognostic scores for intracranial bleeding. Multivariable Cox regression was used to analyze distinct variables for the early (≤90 days) and late (>90 days) phases, with comparative validation against existing scores (modified ACCP, RIETE, VTE-BLEED, and CHAP). RESULTS: Intracranial bleeding occurred in 411 patients (0.53 %), with 208 cases in the early phase and 203 in the late phase. The 30-day mortality was 45 % and 35 %, respectively. Shared significant predictors for both phases include baseline abnormal mental status, brain cancer, recent intracranial bleeding, and epilepsy. Unique to early-phase bleeding were body weight, non-brain cancer, hypertension, dementia, thrombocytopenia, renal insufficiency, and thrombolytic therapy. Advanced age, pulmonary embolism initially, prior stroke, depression, treatment with direct oral anticoagulants, and use of corticosteroids predicted late-phase bleeding. Both prognostic scores showed a c-statistic of 0.68, outperforming existing scores. CONCLUSIONS: The study introduces two temporal prognostic scores for intracranial bleeding during anticoagulation for VTE. By discerning specific risk factors pertinent to each treatment phase, these scores outperform traditional models, offering an advanced tool for clinical decision-making. They hold significant potential for optimizing anticoagulation management and reducing bleeding-related mortality.

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BACKGROUND: Step-based dosing of anticoagulants has been widely implemented for the treatment of coronavirus disease 2019 (COVID-19), but no studies have comprehensively evaluated the effectiveness and safety of this approach. We aimed to investigate whether step-based dosing of anticoagulants was associated with clinical outcomes in patients with COVID-19 compared with standard prophylactic dosing. METHOD: We conducted a retrospective cohort study on adults hospitalized with moderate-to-severe COVID-19. The exposure was step-based dosing of anticoagulants, including prophylactic anticoagulants (PrA), prophylactic-switching-to-therapeutic anticoagulants (Pr-to-ThA), therapeutic anticoagulants (ThA), and therapeutic-switching-to-prophylactic anticoagulants (Th-to-PrA). The primary effectiveness outcome was a composite of all-cause mortality, admission to an intensive care unit (ICU admission), stroke, and venous thromboembolism (VTE). The primary safety outcome was a composite of major and minor/clinically relevant non-major (CRNM) bleeding. RESULTS: Among 1,081 records for analysis (mean age 59.9, 49.9% being female), during a median follow-up of 15 days, the primary effectiveness outcome occurred in 333 patients (33.5% in the PrA group, 24.6% in the Pr-to-ThA group, 23.7% in the Th-to-PrA group, and 38.0% in the ThA group). Compared with the PrA group, patients receiving Pr-to-ThA had a lower risk of the primary effectiveness outcome (adjusted odds ratio (OR) 0.64, 95% CI: 0.45 to 0.90, Dunnett-adjusted p = 0.01), while those in the Th-to-PrA and ThA were more likely to experience the primary safety outcome (Th-to-PrA, aOR = 3.00, 95% CI: 1.53 to 5.89; ThA, aOR = 3.05, 95% CI: 1.61 to 5.79). CONCLUSION: In adults hospitalized with moderate-to-severe COVID-19, compared with standard PrA, the step-based dose-increasing therapy was associated with a lower composite risk of all-cause mortality, ICU admission, stroke, or VTE without evidence of a higher risk of bleeding. ThA dosing was associated with an increase in the bleeding risk, primarily minor and CRNM bleeding.

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INTRODUCTION: Venous thromboembolism (VTE) remains a major complication after total hip arthroplasty (THA), irrespective of the surgical approach. This study investigated the incidence of VTE in patients undergoing THA through intermuscular minimally invasive surgical techniques, which included a direct anterior approach (DAA), an anterolateral approach (AL), and an anterolateral supine approach (ALS), at a single institution. METHODS: A hundred consecutive patients treated with each surgical approach were evaluated. Plasma D-dimer levels one month preoperatively and one day postoperatively, operative time, and intraoperative blood loss were recorded, and the presence of VTE was evaluated based on multidetector-row computed tomography performed the day after surgery. Student's t-test and Pearson's chi-square test or one-way analysis of variance were used in statistical analysis. RESULTS: No differences among the groups in terms of age, height, weight, operative time, intraoperative bleeding, and preoperative and postoperative D-dimer levels were observed. The overall incidence of VTE was 21%. The incidences of VTE were 30% in AL, 17% in ALS, and 16% in DAA, representing a significantly higher rate in AL than in ALS and DAA (P=0.025). The incidences of VTE on the operated side were 19% in AL, 13% in ALS, and 12% in DAA, with no statistically significant differences. The incidences of VTE on the non-operated side were 22% in AL, 9% in ALS, and 8% in DAA; these differences were statistically significant (P=0.0045). DISCUSSION: Results showed that the incidence of VTE was significantly higher in AL than in ALS and DAA, especially for the non-operated side.

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Background: While national guidelines recommend Venous Thromboembolism (VTE) risk assessment in cancer outpatients and consideration of pharmacologic prophylaxis in high-risk patients, prophylaxis rates are low in community oncology practices. A successful model for guideline implementation (the Vermont Model, VM) is validated in an academic tertiary oncology setting. We undertook an implementation study to determine the success of this model in a multi-site community oncology practice. The study objectives were to: 1) adapt the VM to the community practice setting; 2) implement the adapted VM into practice; and 3) evaluate clinical and implementation outcomes. Methods: The study was carried out in three phases: (1) Pre-implementation, a multidisciplinary team addressed the need to adapt the VM to the local context including electronic medical record (EMR) optimisation and clinician education; (2) implementation of the strategies adapted to the local context, informed by VM and adapted based on stakeholder feedback; (3) prospective evaluation of clinical and implementation outcomes at six months after implementation. Findings: Following creation of a comprehensive initiation roadmap for the adaptation of VM program to the community practice, 302 cancer outpatients initiating new treatment met inclusion criteria over a 6 month implementation period. VTE risk education was provided to 100% of patients, and 98% (296) of patients received a VTE risk assessment. Of 52 patients (18%) who scored as high risk based on a modified Khorana (Protecht) score, 14 (27%) initiated prophylaxis. Barriers to program adaptation included EMR optimization challenges and practice-level responsibility assignment, time constraints, concern about potential drug interactions, and financial & insurance issues. Interpretation: Implementation of a multidisciplinary VTE prevention model in the community-based oncology setting successfully increased VTE education and risk assessment rates. AC prophylaxis rates were modestly increased, highlighting the need to understand and address barriers to anticoagulant prophylaxis prescribing in this setting. Funding: Northern New England Clinical Oncology Society Research Funding Program.

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Nitrous oxide (N2O) has a lengthy history of use as an anesthetic and has recently found popularity as a recreational euphoric hallucinogen. The odorless, colorless, non-flammable gas interferes with Vitamin B12 resulting in a cascade of effects, including hyperhomocysteinemia. It has long been proposed that hyperhomocysteinemia adversely affects the cardiovascular system, producing atherogenic and prothrombotic diseases. In this case vignette, we describe a case in which a healthy patient presented with venous thromboembolism (VTE) that we suspect could have been precipitated by daily and significant recreational use of N2O. Anticoagulation therapy was given, and there was a significant improvement in the pulmonary emboli. As recreational use of N2O increases, it is essential to recognize that hyperhomocysteinemia may also produce a thrombotic state.

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Deep vein thrombosis is one of the main causes of inpatient and outpatient morbidity, both in medical and surgical patients, significantly impacting mortality statistics and requiring prompt diagnosis so that treatment can be initiated immediately. This document was prepared and reviewed by 11 specialists certified by the Brazilian Society of Angiology and Vascular Surgery, who searched the main databases for the best evidence on the diagnostic (physical examination, imaging) and therapeutic approaches (heparin, coumarins, direct oral anticoagulants, fibrinolytics) to the disease.

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BACKGROUND: The European Chronic Thromboembolic Pulmonary Hypertension registry (CTEPH), conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. METHODS: Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. RESULTS: Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Oof patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes/(s·cm-5). During an observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (P<0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non-vitamin K oral anticoagulants (P=0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. CONCLUSIONS: This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. REGISTRATION: URL https://clinicaltrials.gov; Unique identifier: NCT02656238.

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Background: A recent clinical trial suggested aspirin is a viable alternative to enoxaparin for venous thromboembolism (VTE) prophylaxis in patients after orthopedic trauma. The initial impact of these findings on VTE prophylaxis prescribing is unknown. The study aimed to evaluate stated VTE prophylaxis prescribing patterns among clinicians who treat patients after orthopedic trauma. Methods: For this clinical vignette survey, we recruited surgeons and advanced practice providers who prescribed VTE prophylaxis to patients with orthopedic trauma across 40 states. Clinicians were shown seven clinical vignettes describing hypothetical patients with orthopedic trauma based on their fracture type, treatment, VTE risk factors, additional injuries and health insurance status. We assessed the stated VTE prophylaxis medications prescribed in-hospital and at discharge, patient factors associated with changes in medication prescribing preferences and practice variation by specialty and provider training. Results: Among the 287 respondents, the median age was 43 years (IQR, 38-50), and 154 (weighted average, 63%) were men. For in-hospital VTE prophylaxis, enoxaparin was prescribed in 83% of the presented scenarios, and aspirin was prescribed in 13% (p<0.001). At discharge, aspirin was prescribed more frequently than enoxaparin (50% vs 41%, p<0.001). Healthcare providers with an aspirin discharge preference were 12% more likely to switch to enoxaparin if the patient had additional VTE risk factors, such as obesity (95% CI 4% to 19%, p=0.005). Conclusions: Despite new clinical evidence, in-hospital VTE prophylaxis prescribing practices for patients with orthopedic trauma remain consistent with those reported a decade ago. However, compared with historical data, clinicians have significantly increased their preference for aspirin for thromboprophylaxis at discharge-unless the patient has additional thromboembolic risk factors. Level of evidence: 5-expert opinion.

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Background: Guidelines recommend pharmacological venous thromboembolism (VTE) prophylaxis only for high-risk patients, but the probability of VTE considered "high-risk" is not specified. Our objective was to define an appropriate probability threshold (or range) for VTE risk stratification and corresponding prophylaxis in medical inpatients. Methods: Patients were adults admitted to any of 10 Cleveland Clinic Health System hospitals between December 2020 and August 2021 (N = 41,036). Hospital medicine physicians and internal medicine residents from included hospitals were surveyed between June and November 2023 (N = 214). We compared five approaches to determining a threshold: decision analysis, maximizing the sensitivity and specificity of a logistic regression model, deriving a probability from a point-based model, surveying physicians' understanding of VTE risk, and deriving a probability from physician behavior. For each approach, we determined the probability threshold above which a patient would be considered high-risk for VTE. We applied each threshold to the Cleveland Clinic VTE risk assessment model (CCM) and calculated the percentage of the 41,036 patients in our cohort who would be considered eligible for prophylaxis due to their high-risk status. We compared these hypothetical prophylaxis rates with physicians' observed prophylaxis rates. Results: The different approaches yielded thresholds ranging from 0.3% to 5.4%, corresponding inversely with hypothetical prophylaxis rates of 0.2% to 75%. Multiple thresholds clustered between 0.52% to 0.55%, suggesting an average hypothetical prophylaxis rate of approximately 30%, whereas physicians' observed prophylaxis rates ranged from 48% to 76%. Conclusions: Multiple approaches to determining a probability threshold for VTE prophylaxis converged to suggest an optimal threshold of approximately 0.5%. Other approaches yielded extreme thresholds that are unrealistic for clinical practice. Physicians prescribed prophylaxis much more frequently than the suggested rate of 30%, indicating opportunity to reduce unnecessary prophylaxis. To aid in these efforts, guidelines should explicitly quantify high-risk.

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BACKGROUND: Acute pulmonary embolism (APE) is a major type of venous thromboembolism (VTE) with a high risk of mortality and disability. There is a lack of biomarkers for APE to indicate deteriorating development and predict adverse outcomes. This study evaluated the significance of miR-150-5p in APE aiming to explore a novel potential biomarker for APE. METHODS: The study enrolled APE (n = 137) and deep wein thrombosis (DVT, n = 67) patients and collected plasma samples from all study subjects. The expression of miR-150-5p was analyzed by PCR and its significance in screening APE and pulmonary arterial hypertension (PAH) was assessed by receiver operating curve (ROC) and logistic analyses. The study established oxidized low-density lipoprotein (ox-LDL)-induced human venous endothelial cells (HUVECs). Through cell transfection combined with cell counting kit-8 (CCK8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA), the effect of miR-150-5p on ox-LDL-induced HUVEC injury was evaluated. RESULTS: Significant downregulation of miR-150-5p was observed in the plasma of APE patients compared with DVT patients (P < 0.0001). The plasma miR-150-5p levels in APE patients occurred PAH was much lower than in patients without PAH (P < 0.0001). Reducing miR-150-5p distinguished APE patients from DVT patients (AUC = 0.912) and was identified as a risk factor for the occurrence of PAH in APE patients (OR = 0.385, P = 0.010). In HUVECs, oxidized low-density lipoprotein (ox-LDL) caused inhibited cell proliferation, enhanced apoptosis, increased pro-inflammatory cytokines, reactive oxygen species (ROS), malondialdehyde (MDA), and decreased superoxide dismutase (SOD). Overexpressing miR-150-5p could promote proliferation, inhibit apoptosis, and alleviate inflammation and oxidative stress of ox-LDL-treated HUVECs. CONCLUSIONS: Downregulated plasma miR-150-5p served as a diagnostic biomarker for APE and predicted the predisposition of PAH in APE patients. Overexpressing miR-150-5p could alleviate ox-LDL-induced endothelial cell injury in HUVECs.

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Comprehensive studies on the incidence, risk factors, and prophylactic measures related to venous thromboembolism (VTE) are lacking in burn care. This study characterizes VTE risk and existing prevention measures to improve and inform overall patient care in the field of burn care on a national scale. The US National Trauma Data Bank (NTDB) was queried from 2007 to 2021 to identify burn-injured patients. Descriptive statistics and multivariate regression analyses were used to explore the association between demographic/clinical characteristics and VTE risk as well as compare various VTE chemoprophylaxis types. There were 326,614 burn-injured patients included for analysis; 5,642 (1.7%) experienced a VTE event during their hospitalization. Patients with VTE were significantly older, had greater BMIs and %TBSA, and were more likely to be male (p<0.001). History of smoking, hypertension or myocardial infarction, and/or substance use disorder were significant predictors of VTE (p<0.001). Patients who received low molecular weight heparin (LMWH) were less likely to have VTE compared to patients treated with heparin when controlling for other VTE risk factors (OR: .564 95% CI .523-.607, p<0.001). Longer time to VTE chemoprophylaxis (>6 hours) initiation was significantly associated with VTE (OR=1.04 95% CI 1.03=1.07, p<0.001). This study sheds light on risk factors and chemoprophylaxis in VTE to help guide clinical practice when implementing prevention strategies in burn patients. This knowledge can be leveraged to refine risk stratification models, inform evidence-based prevention strategies, and ultimately enhance the quality of care for burn patients at risk of VTE.

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INTRODUCTION: Venous thromboembolism (VTE) poses a significant risk in colorectal cancer surgeries due to hypercoagulability and the anatomical challenges of the pelvic cavity. With the advancement of minimally invasive techniques, intraoperative strategies for preventing VTE may prove to be effective. This study explores the effects of intraoperative pneumoperitoneum pressures on VTE incidence following colorectal cancer surgeries. METHODS: This single center parallel randomized controlled double-blind, trial involved 302 patients undergoing elective laparoscopic or robotic colorectal surgery. Patients were randomized to either a standard pneumoperitoneum pressure group (SP: 15 mmHg) or a low-pressure group (LP: 10 mmHg). Primary outcomes measured were the incidence of VTE, including symptomatic and asymptomatic DVT and PE. Secondary outcomes included postoperative D-dimer levels, surgery duration, blood loss, surgeon satisfaction, and oncological quality. RESULTS: Out of 302 randomized patients, 275 were evaluable post exclusions, with 138 in the SP group and 137 in the LP group. The incidence of VTE was 10.9 % in the SP and 13.9 % in the LP group, with no significant difference between the two (P = 0.450). Secondary outcomes such as D-dimer levels, surgery duration, and blood loss showed no significant differences between two groups. Surgeon satisfaction and oncological outcomes were similarly comparable. CONCLUSIONS: The trial demonstrated no significant difference in the incidence of VTE between standard and low pneumoperitoneum pressures. This suggests that lower pressures may not necessarily provide a benefit in reducing postoperative VTE in colorectal cancer surgeries.

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BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Despite this, studies show that patients with cancer feel inadequately informed about the VTE risk and symptoms, which may impede their ability to recognise symptoms and react promptly. Patients with lung cancer are especially vulnerable due to a high relative risk of developing VTE combined with a high prevalence of low health literacy. This study aimed to explore the VTE information needs of lung cancer patients and how patients and healthcare professionals (HCPs) communicate about VTE. MATERIAL AND METHODS: Data was collected via semi-structured interviews with patients with lung cancer and HCPs. All participants (n = 20) were recruited from an oncological department. The analysis was performed in an inductive manner using a Ricoeur inspired strategy. FINDINGS: Patients had varying information needs regarding VTE, but HCPs did not routinely communicate about VTE, as the topic tended to be lowly prioritised. HCPs communicated about VTE when patients expressed a need or presented symptoms of VTE. HCPs expressed concerns about adding to patient's emotional burden by informing about VTE, while some patients emphasised the importance of being mentally prepared for potential complications. CONCLUSION: The study demonstrates the challenging balance HCPs must maintain between adequately communicating about VTE and not causing undue psychological distress. However, given patient's often limited awareness of VTE, the responsibility to initiate communication about VTE must fall on the HCPs.

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Cerebral venous sinus thrombosis (CVST) is an uncommon site of venous thromboembolism. CVST more commonly affects younger people and women, in stark contrast to other forms of venous thrombosis where incidence increases with age and overall affects men. Traditional risk factors for the development of CVST include endogenous and exogenous estrogen (combined oral contraceptives and pregnancy and the puerperium), thrombophilias and rare haematologic disorders. New and emerging risk factors include obesity, polycystic ovary syndrome, COVID-19 infection, and vaccine-induced thrombocytopenia and thrombosis (VITT) and VITT-like disorders. Management centres around anticoagulation, managing the underlying cause, and consideration of invasive measures including endovascular thrombolysis and/or thrombectomy and craniectomy for severe cases. This review discusses the emerging risk factors and their identification, evidence for treatment including the use of direct oral anticoagulants, and the role of invasive management options.

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BACKGROUND: Although guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown. OBJECTIVE: To determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services. DESIGN: Cohort study using electronic health record data from adult patients hospitalized on medical services at four academic medical centers between 2016 and 2019. PARTICIPANTS: Among 111,550 admissions not on intermediate or full-dose anticoagulation, 48,520 (43.5%) received HA-VTE pharmacoprophylaxis on the day of or the day after admission. MAIN MEASURES: Candidate predictors of HA-VTE pharmacoprophylaxis initiation, including known HA-VTE risk factors, predicted HA-VTE risk, and bleeding diagnoses present on admission. KEY RESULTS: After adjustment for age, sex, race/ethnicity, and study site, the strongest clinical predictors of HA-VTE pharmacoprophylaxis initiation were malnutrition and chronic obstructive pulmonary disease. Thrombocytopenia and history of gastrointestinal bleeding were associated with decreased odds of HA-VTE pharmacoprophylaxis initiation. Patients in the highest two tertiles of predicted HA-VTE risk were less likely to receive HA-VTE pharmacoprophylaxis than patients in the lowest (1st) tertile (OR 0.84, 95% CI [0.81, 0.86] for 2nd tertile, OR 0.95, 95% CI [0.92, 0.98] for 3rd tertile). CONCLUSIONS: Among patients not already receiving anticoagulants, HA-VTE pharmacoprophylaxis initiation during the first two hospital days was lower in patients with higher predicted HA-VTE risk and those with risk factors for bleeding. Reasons for not initiating pharmacoprophylaxis in those with higher predicted risk could not be assessed.

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Traumatic brain injury (TBI) presents complex management scenarios, particularly in patients requiring anticoagulation for concurrent conditions such as venous thromboembolism (VTE) or atrial fibrillation (AF). A systematic search of PubMed/MEDLINE, Embase, and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria encompassed studies assessing the effects of anticoagulation therapy on outcomes such as re-hemorrhage, hematoma expansion, thrombotic events, and hemorrhagic events in TBI patients with subdural hematomas (SDH). This systematic review critically addresses two key questions: the optimal timing for initiating anticoagulation therapy and the differential impact of this timing based on the type of intracranial bleed, with a specific focus on subdural hematomas (SDH) compared to other types. Initially screening 508 articles, 7 studies met inclusion criteria, which varied in design and quality, precluding meta-analysis. The review highlights a significant knowledge gap, underscoring the lack of consensus on when to initiate anticoagulation therapy in TBI patients, exacerbated by the need for anticoagulation in the presence of VTE or AF. Early anticoagulation, particularly in patients with SDH, may elevate the risk of re-hemorrhage, posing a clinical dilemma. Evidence on whether the type of intracranial hemorrhage influences outcomes with early anticoagulation remains inconclusive, indicating a need for further research to tailor management strategies effectively. This review underscores the scarcity of high-quality evidence regarding anticoagulation therapy in TBI patients with concurrent conditions, emphasizing the necessity for well-designed prospective studies to elucidate optimal management strategies for this complex patient population.

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BACKGROUND: The ONCO DVT study demonstrated potential benefits of extended edoxaban treatment in patients with isolated distal deep vein thrombosis in terms of thrombotic risk. However, the risk-benefit balance in patients with anemia remains unclear. METHODS AND RESULTS: This prespecified subgroup analysis included 601 patients, divided into anemia (n=402) and no-anemia (n=199) groups. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death. Anemia was defined as hemoglobin <12 g/dL for women and <13 g/dL for men. In the anemia subgroup, the primary endpoint occurred in 3 (1.5%) and 17 (8.4%) patients in the 12- and 3-month edoxaban treatment groups, respectively (odds ratio [OR] 0.17; 95% confidence interval [CI] 0.05-0.58), compared with 0 and 5 (4.9%) patients, respectively, in the no-anemia subgroup (P interaction=0.997). Major bleeding occurred in 26 (13.1%) and 17 (8.4%) patients with anemia in the 12- and 3-month edoxaban treatment groups, respectively (OR 1.64; 95% CI 0.86-3.14), compared with 2 (2.1%) and 5 (4.9%) patients without anemia (OR 0.67; 95% CI 0.26-1.73; P interaction=0.13). CONCLUSIONS: Regardless of the presence of anemia, edoxaban treatment for 12 months was superior to treatment for 3 months in reducing thrombotic events, whereas the risk of major bleeding did not differ significantly between the 2 treatment groups.

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Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. While various inflammatory conditions have been linked to venous thromboembolism (VTE), the risk of VTE among patients with AD remains unclear. We sought to systematically review and meta-analyze population-based studies to determine the association between AD and incident VTE. A systematic review was performed of published studies in PubMed, Web of Science, Embase and Cochrane library from their inception to 27 May 2024. At least two reviewers conducted title/abstract, full-text review and data extraction. Cohort studies examining the association of AD with incident VTE were included. Quality of evidence was assessed using the Newcastle-Ottawa Scale. Six cohort studies, encompassing a total of 10,186,861 participants, were included. The meta-analysis revealed a significantly increased risk for incident VTE among AD patients (pooled hazard ratio (HR), 1.10; 95% CI, 1.00-1.21), with an incidence rate of VTE at 3.35 events per 1000 patient-years. Individual outcome analyses suggested that AD was associated with higher risks of deep vein thrombosis (pooled HR, 1.15; 95% CI, 1.04-1.27) but not pulmonary embolism (pooled HR, 0.99; 95% CI, 0.87-1.13). This systematic review and meta-analysis indicated an increased risk of incident VTE among patients with AD. Future studies are necessary to elucidate the underlying pathophysiology of the association between AD and VTE.

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BACKGROUND: Protein S (PS) is an anticoagulant that functions as a cofactor for activated protein C (APC) and tissue factor pathway inhibitor. PS deficiency is a risk factor for venous thromboembolism. PS activity is commonly measured using clot-based assays involving fibrin and thrombin production, but improvements are needed. OBJECTIVES: To develop a new assay for measuring plasma PS activity by quantifying the amount of activated coagulation factor V (FVa) cleaved by APC. METHODS: We designed a recombinant, modified FV (FVm) that mimicked FVa. We analyzed 160 purposively selected plasma samples from the Biobank of the National Cerebral and Cardiovascular Center. RESULTS: The assay using mixed normal and PS-deficient plasma detected FVm cleavage in a PS concentration-dependent manner. The correlation between PS activity, measured using the FVm cleavage assay, and free PS antigen levels was relatively weak. We then sequenced all exons of PROS1 from 47 subjects with <60% activity in either the FVm cleavage assay or the clot-based assay. Nonsynonymous variants were identified in 12 of 24 subjects with <60% activity in both assays and in 2 of 7 subjects with <60% activity in the FVm cleavage assay alone. No variants were identified in 16 subjects with <60% activity in the clot-based assay alone. Unlike the clot-based assay, the FVm cleavage assay was not affected by the presence of rivaroxaban in the plasma. CONCLUSIONS: An assay using the FVm substrate may be less susceptible to interference and provide a more accurate evaluation of plasma PS activity than clot-based assays.

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Venous thromboembolism (VTE) presents a notable healthcare burden, particularly among the elderly, who experience increased risks and more severe complications. This review aims to use the extensive data from the RIETE registry, a comprehensive database on consecutive patients with VTE. We examine the clinical features, therapeutic approaches, and patient outcomes of VTE in elderly patients, compared to younger patients, offering a comprehensive understanding of management challenges and emphasizing the need for strategies that accommodate the unique challenges of this population.