The epidemiology of venous thromboembolic events in a severe trauma cohort admitted to the intensive care unit of an Australian major trauma centre over a five-year period.

Core regulatory mechanisms of macrophage dynamic polarization and multicellular interaction networks in driving venous thromboembolism.

MicroRNAs (miRNAs) are small regulatory molecules that control protein synthesis, presenting promising opportunities for novel, mechanism-based therapies. Their roles are essential in the biological processes underlying thrombosis, including vascular function, coagulation, and platelet activity. Specific miRNAs, such as miR-126 and miR-223, that influence platelet activation and adhesion are particularly relevant to thrombotic disorders, including deep vein thrombosis (DVT) and pulmonary embolism (PE). This positions them as intriguing targets for new therapeutic strategies. miRNA-based treatments, using synthetic mimics or inhibitors (antagomirs), offer a potential avenue for precisely modulated anticoagulant therapy. However, these approaches remain in early-stage development. Significant challenges must be overcome before miRNA therapies can achieve widespread clinical adoption. Further research is essential to elucidate miRNA function in venous thromboembolism (VTE) fully and to translate these insights into safe and effective treatments. This review summarizes current knowledge of the role of miRNAs in VTE, underscores their substantial therapeutic potential, and addresses the critical obstacles and practical limitations that must be resolved to realize their full promise in treating thrombotic diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. Menopause is associated with increased hepatic fat deposition and thus metabolic dysfunction, contributing to heightened risk of progressive liver and cardiovascular disease. Hormone replacement therapy (HRT), supported by pre-clinical data, may be associated with a lower risk. We performed a retrospective cohort study using the TriNetX global federated research network. Eligible participants were peri-menopausal women (ICD-10 codes N95/Z78.0, AND age 40-65 years) with pre-existing MASLD (based on ICD-10 codes K76.0/K75.81 or positive modified hepatic steatosis index plus ≥ 1 metabolic syndrome, MetS, trait). Patients initiating HRT (oestrogen ± progesterone) were compared with untreated controls using 1:1 propensity score matching for demographics, comorbidities, biochemistry and medications. The primary outcome was a composite of major adverse liver outcomes (MALO: portal hypertension, varices, ascites, spontaneous bacterial peritonitis, encephalopathy, hepatorenal/pulmonary syndromes, cirrhosis, decompensated liver disease, hepatocellular carcinoma, liver transplant). Secondary outcomes were individual MALO components, type 2 diabetes (T2D), major adverse cardiovascular events (MACE), breast and endometrial cancer, and venous thromboembolism (VTE). Cox regression generated hazard ratios (HRs) with 95% CIs over 5 years. Sensitivity analyses adjusted for geography, hormone type, and degree of obesity. After matching, 21 639 patients were included in each treatment arm. HRT was associated with a significantly reduced risk of MALO (HR 0.80; 0.71, 0.9), largely driven by reductions in ascites and SBP (0.78; 0.64, 0.95), and liver cirrhosis (0.75; 0.63, 0.90), and reduced risk of cardiometabolic outcomes: T2D (0.90; 0.84, 0.96), and MACE (0.90; 0.83, 0.98). HRT was not associated with increased risk of breast cancer or VTE, whilst endometrial cancer risk was reduced (0.49; 0.40, 0.61). Oestrogen was linked to greater benefits compared to progesterone, and patients with mild-moderate obesity experienced more significant risk reduction. Treatment of peri-menopausal symptoms with HRT, in patients with pre-existing MASLD, is associated with a lower 5-year risk of major liver and cardiometabolic disease. These findings support early basic science research and should prompt a closer examination through clinical trials.

Development of clinical manifestations in individuals positive for antiphospholipid antibodies according to the 2023 ACR/EULAR serological domains.

Post-traumatic care is evolving from a reactive, protocol-driven paradigm to a predictive, personalized approach. This review examines how artificial intelligence and machine learning are redefining postoperative management by predicting complications before they manifest. Recent literature (2023-2025) highlights three major advances: (a) the validation of gradient boosting algorithms (e.g. Extreme Gradient Boosting) that significantly outperform traditional scoring systems for predicting trauma-induced coagulopathy; (b) the development of interpretable, phenotype-specific models for venous thromboembolism risk stratification, particularly in traumatic brain injury; and (c) the emergence of real-time sepsis prediction tools that account for the sterile inflammation inherent to trauma. However, a recurring limitation in current research is the reliance on retrospective datasets and single-center validations, underscoring the critical need for rigorous external validation across diverse patient populations before widespread clinical adoption. Artificial intelligence is not merely a monitoring tool but a driver of precision medicine in trauma. By leveraging diverse modalities, from computer vision in radiology to natural language processing in electronic health records, clinicians can now anticipate adverse events. To bridge the gap between algorithm and bedside, future efforts must focus on overcoming significant implementation barriers, such as data interoperability, and ensuring model generalizability.

Janus kinase inhibitors (JAKis) have emerged as effective treatments for several skin immune-mediated inflammatory diseases (IMIDs). However, safety concerns have been raised due to boxed warnings from rheumatoid arthritis trials, and whether these risks apply to skin IMIDs remains uncertain. This multinational retrospective cohort study used the TriNetX database to compare the real-world safety of JAKis and conventional immunomodulators (cIMs) in patients aged 12 years or older with skin IMIDs (psoriatic disease, atopic dermatitis, or alopecia areata). Patients newly prescribed JAKis (tofacitinib, upadacitinib, deucravacitinib, baricitinib, abrocitinib, or ritlecitinib) were propensity score-matched (1:1) with those prescribed cIMs (methotrexate or cyclosporine) based on demographics, baseline skin IMIDs, and comorbidities, yielding 17,068 matched patients. Over 2 years, the JAKi cohort showed lower incidences of all-cause mortality (0.28% vs. 0.62%; P = 0.015) and major adverse cardiovascular events (MACE; 1.15% vs. 1.95%; P = 0.005) than the cIM cohort, corresponding to reduced risks (mortality: HR, 0.47; 95% CI, 0.25-0.88; MACE: HR, 0.63; 95% CI, 0.46-0.88). Risks of venous thromboembolism (HR, 0.80; 95% CI, 0.43-1.48) and malignancy (HR, 0.85; 95% CI, 0.63-1.16) were not increased. Subgroup analyses, including older adults and those with cardiometabolic risk factors, showed no signal of increased risk, with consistent findings across available agent-level and sensitivity analyses. These results suggest that, over 2 years, JAKis are not associated with increased risks of mortality, MACE, venous thromboembolism, or malignancy compared with conventional systemic agents in patients with skin IMIDs.

Thromboembolic cardiovascular diseases (CVD), including acute coronary syndromes, ischemic stroke, and venous thromboembolism, remain a leading cause of morbidity and mortality worldwide. Despite significant improvements in prevention and diagnosis, thromboembolic CVD remains a major global health challenge, reflecting the incomplete control of multifactorial vascular risk. Growing evidence indicates that air, noise, and light pollution are important yet underrecognized contributors to cardiovascular morbidity. Exposure to particulate matter (PM2.5, PM10), gaseous pollutants (NO2, SO2, CO, O3), chronic noise, and artificial light at night promotes endothelial dysfunction, oxidative stress, inflammation, and platelet activation-key mechanisms fostering a prothrombotic setting. Although regulatory progress has been achieved, air pollution remains the most significant environmental determinant of cardiovascular health globally, and the combined effects of coexisting pollutants are not fully understood. The convergence of urbanization, industrialization, and increasing light exposure further amplifies environmental impacts on vascular health. This scientific statement aims to synthesize current epidemiological and mechanistic evidence, highlight the complex interactions among air, noise, and light pollution, identify critical research gaps, and provide a comprehensive conceptual framework for understanding how environmental stress contributes to thromboembolic cardiovascular complications. Strengthening multidisciplinary research, integrating exposome-based data, and implementing effective prevention policies are essential steps toward mitigating the cardiovascular burden of environmental pollution.

Late Venous Thromboembolism Chemoprophylaxis and Increased Risk of Deep Venous Thrombosis, Pulmonary Embolism, and Mortality in Patients with Traumatic Spinal Injury.

Letter to the Editor: High Risk of Venous Thromboembolism With Aspirin Prophylaxis After THA for High-riding Developmental Dysplasia of the Hip: A Retrospective, Comparative Study.

Contraception is essential for reproductive health and women's empowerment because it allows informed choices about pregnancy prevention. Oral contraceptives (OCs) are a popular method due to their accessibility and high level of effectiveness in attaining contraception through the suppression of ovulation. However, current OC regimens do not consider circadian hormonal rhythms, which significantly influence hormone secretion and drug metabolism. Accounting for circadian rhythms may further reduce the dosage of current formulations, which pose risks, including an increased likelihood of venous thromboembolism. We addressed this gap by developing a mathematical model that integrates circadian rhythms with contraceptive pharmacokinetics. Our results show that daytime OC dosing reduces the required ethinyl estradiol (EE) dose by about 6% and the required dienogest (DNG) dose by about 52% compared to evening dosing, due to the alignment of EE and DNG concentrations with luteinizing hormone (LH) production peaks. We further lowered the EE dose by about 67% using an optimal nonconstant regimen and decreased the number of intake days from 21 to 8. This dual-timescale optimization demonstrates how incorporating circadian rhythms can significantly enhance contraceptive regimens, enabling safer and more effective dosing strategies with broader implications for chronopharmacological interventions.

Nationwide Analysis of Maternal Mortality Due to Venous Thromboembolism.

Testosterone replacement therapy (TRT) is an effective treatment for male hypogonadism of defined etiology, yet its safety profile continues to prompt clinical and regulatory scrutiny. Beyond major adverse cardiovascular events (MACE), attention has shifted toward clinically important non‑MACE outcomes, notably atrial fibrillation (AF), acute kidney injury (AKI), and venous thromboembolism, including pulmonary embolism (PE). The landmark TRAVERSE randomized safety trial in men with hypogonadism and established or high cardiovascular risk demonstrated non‑inferiority of TRT vs. placebo for MACE, but reported higher event rates of AF, AKI and PE in the testosterone group. Observational datasets suggest a possible early venous thromboembolism risk window after TRT initiation (often within the first 3-6 months), although estimates vary and residual confounding remains a major limitation. In February 2025, the US Food and Drug Administration updated testosterone product labeling: the boxed warning for major cardiovascular events was removed, while a class‑wide warning regarding blood pressure increases was added based on ambulatory blood pressure monitoring data. This narrative review integrates randomized and real‑world evidence on TRT‑associated AF, AKI and PE, translates these signals into practical guidance for patient selection and safety monitoring, and outlines key methodological and mechanistic priorities for future research. In contemporary practice, the objective is precision: select the right patient, aim for stable exposure, and follow a protocolized safety plan.

BackgroundApixaban and rivaroxaban are the oral anticoagulants most frequently used to treat acute venous thromboembolism. However, uncertainty remains about the difference in bleeding risk between the two medications.MethodsIn an international trial with a prospective, randomized, open-label, blinded end-point design, we assigned, in a 1:1 ratio, eligible patients with acute symptomatic pulmonary embolism or proximal deep-vein thrombosis to receive apixaban or rivaroxaban for 3 months. Apixaban was given at a dose of 10 mg twice daily for 7 days followed by 5 mg twice daily, and rivaroxaban was given at a dose of 15 mg twice daily for 21 days followed by 20 mg daily. The primary outcome was clinically relevant bleeding, a composite of major bleeding or clinically relevant nonmajor bleeding, as defined according to the International Society on Thrombosis and Haemostasis, during the 3-month trial period. Secondary outcomes included death from any cause.ResultsA total of 2760 patients underwent randomization: 1370 to the apixaban group and 1390 to the rivaroxaban group. A primary-outcome event occurred in 44 of 1345 patients (3.3%) in the apixaban group and 96 of 1355 patients (7.1%) in the rivaroxaban group (relative risk, 0.46; 95% confidence interval [CI], 0.33 to 0.65; P<0.001). Death from any cause occurred in 1 patient (0.1%) in the apixaban group and in 4 patients (0.3%) in the rivaroxaban group (relative risk, 0.25; 95% CI, 0.03 to 2.26). Serious adverse events unrelated to bleeding or venous thrombosis occurred in 36 patients (2.7%) in the apixaban group and in 30 patients (2.2%) in the rivaroxaban group.ConclusionsAmong patients with acute venous thromboembolism, the risk of clinically relevant bleeding was significantly lower with apixaban than with rivaroxaban during the 3-month treatment period. (Funded by the Canadian Institutes of Health Research and others; COBRRA ClinicalTrials.gov number, NCT03266783.)

The purpose of this report is to highlight a case of utilizing weight-based enoxaparin for prophylaxis of venous thromboembolism (VTE) in an elderly, extremely underweight patient. VTE represents a significant concern for hospitalized patients. There is a dearth of literature regarding utilization of low-molecular-weight heparins such as enoxaparin or unfractionated heparin in patients who are underweight. In this case, a 68-year-old female who was extremely underweight (21.8 kg) presented to the emergency department in acute respiratory distress secondary to pneumonia and a chronic obstructive pulmonary disease exacerbation. The patient had a Padua score of 5 and an IMPROVE score of 2 that signified the necessity of pharmacologic VTE prophylaxis. A clinical decision was made to utilize a weight-based enoxaparin dosing strategy for VTE prophylaxis using a pediatric dilution to deliver the dose. Enoxaparin was initiated at 0.5 mg/kg (10 mg) subcutaneously daily and monitored via anti-factor Xa peak levels to verify that the dose provided an adequate prophylactic level. Ultimately, a dose of 0.5 mg/kg resulted in an appropriate anti-factor Xa level of 0.21 units/mL, equating to suitable VTE prophylaxis. A review of the literature revealed little evidence for optimal anticoagulation dosing for VTE prophylaxis in adult patients weighing under 40 kg. Various adjustment strategies have been utilized; however, there is no available evidence pertaining to patients at the extreme of low weight represented by the reported case or to attainment of an anti-factor Xa level within the therapeutic range in such patients. This case represents the use of a weight-based enoxaparin strategy for an extremely underweight elderly patient and the attainment of a therapeutic prophylactic anti-factor Xa level.

To determine the relationships between subprophylactic anti-Xa levels and low-molecular-weight heparin (LMWH) thromboprophylaxis regimens with venous thromboembolism (VTE) risk, and to identify predictors of subprophylactic anti-Xa levels in critically ill adults. Medline and Embase were searched from inception to May 7, 2025. We included studies enrolling critically ill adults receiving LMWH thromboprophylaxis and assessing the relationship between anti-Xa levels and risk of subprophylactic measurements associated with: 1) standard dosing strategies; 2) VTE risk; or 3) predisposing factors. We extracted or calculated mean, sd, median, interquartile range, mean difference (MD), unadjusted odds ratios (uORs), and adjusted odds ratios (aORs), when available. Risk of bias was evaluated using Cochrane tools. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. We included 39 studies (7124 patients). The proportion of patients receiving LMWH prophylaxis achieving target anti-Xa levels was 47% (95% CI, 36-57%). Subprophylactic anti-Xa levels were associated with an increased risk of VTE (uOR, 2.87; 95% CI, 1.42-5.81; low certainty). Variables with a moderate certainty association with subprophylactic anti-Xa levels include male sex (aOR, 2.65; 95% CI, 1.07-6.56), increased weight (MD, 4.90 kg higher weight compared with those with target levels; 95% CI, 2.78-7.02), and elevated body mass index (MD, 1.36 per kg/m2 higher compared with those with target levels; 95% CI, 0.64-2.09). Less than half of critically ill patients achieved their prophylactic anti-Xa targets despite LMWH thromboprophylaxis. Subprophylactic anti-Xa levels may be associated with an increased risk of VTE. Male sex, increased weight, and elevated body mass index have a moderate certainty association with developing subprophylactic anti-Xa levels. This study highlights the clinical importance of anti-Xa level monitoring in critically ill adults and the need for a future randomized controlled trial to further evaluate this topic.

Reply to the Comment: Research Design Concerns in a TriNetX Analysis of Venous Thromboembolism in Pediatric Cystic Fibrosis Patients.

Hereditary hemorrhagic telangiectasia (HHT) causes severe recurrent epistaxis, chronic gastrointestinal bleeding, solid organ arteriovenous malformations, and significant anemia. Although it is the second most common inherited bleeding disorder worldwide, no approved therapies exist. The multicenter, US randomized, controlled PATH-HHT trial demonstrated efficacy of short-term pomalidomide treatment of epistaxis in HHT. However, questions regarding long-term safety, effectiveness, and utility for HHT-associated gastrointestinal bleeding remain. The PATH-HHT ATLAS (after trial longitudinal assessment study) was a multicenter US longitudinal observational study evaluating patients enrolled in PATH-HHT who continued pomalidomide after PATH-HHT through a poststudy drug access program, with ongoing close monitoring per PATH-HHT protocol and as mandated by the US Food and Drug Administration. Sixty-two patients treated with pomalidomide for HHT for up to 4.4 years were included. Significant, durable improvements in mean epistaxis severity score (5.55 points [baseline] to 2.80 points [month 12]; P< .0001) and mean hematologic support score (9.11 red cell unit equivalents [RUEs] during 6 months pretreatment to 5.73 RUEs [months 7-12]; P = .0056) were observed. Pomalidomide was less effective for gastrointestinal bleeding than for epistaxis, particularly in patients with high red blood cell transfusion requirements. Thirty-one patients (50%) underwent dose reduction from 4 mg daily, primarily due to neutropenia, but most maintained effectiveness at 2 or 3 mg daily. Over 105.2 patient-years of pomalidomide treatment, 0 patients developed peripheral neuropathy, 1 developed venous thromboembolism, and 5 developed serious infections. In conclusion, pomalidomide was effective for HHT-associated epistaxis over extended durations, albeit with nontrivial potential toxicities, and may be considered for certain patients with HHT. This trial was registered at www.clinicaltrials.gov as NCT07018401.

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology, arising from complex interactions between tumor biology, host factors, and anticancer therapies. Growing evidence indicates that biological sex and gender-related factors modulate both thrombotic risk and clinical expression of venous thromboembolism (VTE) in patients with cancer. In this narrative review, we summarize current epidemiological, biological, and clinical data on sex- and gender-related differences in CAT across solid and hematologic malignancies. Men generally exhibit a higher overall incidence of VTE, whereas women may experience earlier, treatment-associated thrombotic events, with variability according to cancer type, stage, and therapy. Biological factors linked to coagulation and inflammation differ between sexes and may contribute to these patterns, although mechanistic evidence remains incomplete. Sex-related disparities also emerge in treatment-associated complications, including bleeding risk and abnormal uterine bleeding in anticoagulated women of reproductive age. In contrast, evidence for sex differences in oncohematology-associated thrombosis is limited and inconsistent. Gender-related inequalities in clinical trial participation further constrain the interpretation of available data. Overall, current evidence supports sex as a clinically relevant modifier of CAT risk, underscoring the need for systematic sex- and gender-informed research, to improve mechanistic understanding, and sex-stratified reporting to advance precision medicine in thrombosis and oncology.

A direct oral anticoagulant is an oral medication that inhibits a specific coagulation factor to prevent thrombus formation. DOACs are primarily used to prevent stroke and systemic embolism in non-valvular atrial fibrillation, to treat and prevent venous thromboembolism, and for postoperative venous thromboembolism prophylaxis in orthopaedic surgery. Anticoagulants prevent thrombus extension and embolic events by decreasing fibrin formation. Anticoagulants do not lyse existing thrombi; rather, they are used to prevent recurrent events. The predictable PK/PD profile, combined with a lower risk of intracranial bleeding compared with vitamin K antagonists, makes direct oral anticoagulants (DOACs) the preferred drugs. However, despite these benefits, there are challenges in clinical practice, including drug interactions, peri-procedural care, and use in patients with renal impairment, hepatic impairment, and cancer. This narrative review supports the safe and effective use of direct oral anticoagulants by evaluating individual bleeding risk factors, using patient-centered strategies for bleeding prevention, monitoring, and management, and highlighting the pharmacist's role in optimizing therapy.