Seminars in thrombosis and hemostasis最新文献

Evidence-based medicine (EBM) has created a revolutionary system for disseminating a scientific method. However, the scientific rigor of early EBM did not demonstrate any concern for ethics in the management of venous thromboembolism (VTE) and atrial fibrillation (AF). We critically reviewed whether EBM and ethical principles have always converged, focusing on the development and use of anticoagulants, by analyzing key trials in the treatment and prevention of those conditions. Moreover, we aimed to explore whether methodological rigor has sometimes overshadowed clinical ethics, particularly in the context of placebo-controlled trials. In our opinion, even if randomized clinical trials (RCTs) are considered the first step in the hierarchy of EBM, several of these appear unjustified, as observational studies had already indicated that anticoagulants (heparins and anti-vitamin K drugs [VKA]) were considered effective in the treatment and prevention of thrombotic diseases, such as VTE and AF. The use of a placebo was often unethical. This has caused unjustified mortality and morbidity to many people when a placebo has been used as a control. Even the methodology in favor of the non-inferiority margin is questionable, as it is considered satisfactory to maintain at least half of the efficacy of the current drug. In other words, a bonus for the new medicines seems to be always generous, and in the future, biocreep phenomenon is destined to be dangerous. The belief that only RCTs, even if of paramount importance, produce trustworthy results and that observational studies are misleading can lead to a disadvantage in patient care, clinical investigation, and the education of health care professionals (visual abstract).

Venous thromboembolism (VTE) remains a major cause of preventable morbidity and mortality. Prophylaxis with anticoagulation is limited by bleeding risk, contraindications, and patient-specific factors. Interest has therefore grown in alternative or adjunctive nonanticoagulant strategies that can mitigate thrombotic risk without increasing bleeding complications. Aspirin has demonstrated efficacy in both primary and secondary prevention of VTE. Most studies and trials have been undertaken in an orthopaedic population but with favorable safety profile. Statins have been shown to reduce VTE incidence without increased bleeding in several trials. Metformin appears to reduce prothrombotic mechanisms in type 2 diabetes. Observational studies have suggested its use to lower VTE risk. However, randomized data are lacking. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been shown to reduce weight, improve metabolic control, and possess anti-inflammatory effects. Evidence suggests GLP-1 RAs may reduce VTE risk. However, findings are inconsistent across observational and trial-based analyses. Other emerging alternatives include hydroxychloroquine, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (post hoc analyses of cardiovascular trials suggesting lower VTE rates potentially via lipoprotein (a) reduction), sodium-glucose cotransporter-2 inhibitors (overall neutral in meta-analyses of randomized control trials with some real-world evidence vs. comparators), and renin-angiotensin-aldosterone system modulators (mixed observational data and no trial-proven benefit). Uncertainties remain regarding optimal patient selection, duration of prophylaxis, and their role in combination with standard anticoagulation across these drug classes. Further studies/trials are warranted to define the efficacy, safety, and guideline positioning of these agents in diverse patient populations.

Arterial and venous thromboembolism represent major contributors to global morbidity and mortality. Despite substantial progress in risk stratification and clinical management, a significant proportion of thromboembolic events occur in individuals not classified within traditional high-risk groups indicating the involvement of additional, non-conventional risk factors in thrombotic pathophysiology.Recent evidence has highlighted the gut microbiome as a critical determinant of human health, with increasing recognition of its role in cardiovascular and thrombotic disorders. Furthermore, the gut microbiome constitutes a modifiable risk factor, offering new horizons for therapeutic intervention and emerging evidence suggests that alterations in the microbiome may significantly impact thrombotic risk.Moreover, microbiome-derived metabolites have gathered considerable scientific attention for their potential involvement in the initiation and progression of thrombosis. These metabolites may serve as novel biomarkers, complementing conventional risk indicators in disease diagnosis, prognosis, screening, and patient monitoring. Microbiome-derived metabolites may hold dual utility, first as diagnostic and prognostic biomarkers, and, second, as potential targets for pharmacologic modulation. Collectively, these findings underscore the growing significance of the gut microbiome as an environmental factor in thromboembolic disease and justify the constantly increasing employment of the scientific community in several aspects of health and disease.

Since their discovery in 2004, neutrophil extracellular traps (NETs) have been at the center of multidisciplinary attention. Although a key tool in neutrophil-mediated immunity, these filamentous, enzyme-enriched DNA-histone complexes can be detrimental to tissues and have been identified as an underlying factor in a range of pathological conditions. Building on more than 20 years of research into NETs, this review places thrombosis, the pathological formation of blood clots, in the spotlight. From this point of view, we discuss the structure and formation of NETs, as well as the interaction of their components with the hemostatic system, dissecting the pathways through which NETs exert their marked effect on formation and the dissolution of thrombi. We pay distinct attention to the latest developments in the research of a key player in NET formation, peptidyl-arginine-deiminase (PAD) enzymes: their types, sources, and potential cross-play with the hemostatic machinery. Besides these molecular details, we elaborate on the link between pathological thrombosis, NETs, and widespread conditions that represent a debilitating public health burden worldwide, such as sepsis and neoplasms. Finally, future implications on the treatment of thrombosis-related conditions will be discussed.

Acute pulmonary embolism (PE) is potentially life-threatening, with up to 15% risk of death. We compared four risk stratification models to identify outpatients at risk of mortality up to 90 days post acute PE. A retrospective cohort study included outpatients aged ≥18 years with confirmed PE from June 1, 2014 to May 31, 2019, identified via diagnostic imaging reports. Simplified Pulmonary Embolism Severity Index (sPESI) and Hestia scores were calculated as per original derivation methods. Patients were stratified by four models: sPESI alone, Hestia alone, sPESI plus right ventricular dysfunction (RVD), and Hestia plus RVD. Model accuracy and discriminatory power for 30- and 90-day mortality were assessed by area under the receiver operating curve (AUC). The study comprised 785 outpatients (mean age 65.0 years; 42.2% male). Overall mortality rates were 4.1% at 30 days and 7.8% at 90 days. sPESI identified 31.5% as low risk versus 19.1% by Hestia. All models demonstrated 100% sensitivity and negative predictive value for 30-day mortality, but modest discriminatory power (AUC range: 59.2-67.1). sPESI consistently outperformed other models in both timeframes. Including RVD with sPESI or Hestia did not enhance accuracy and slightly reduced performance. The net reclassification index indicated minor improvement in non-event classification with RVD, but no benefit for identifying deaths. sPESI remains a modest yet effective predictor of mortality risk within 90 days following acute PE, consistently outperforming sPESI + RVD, Hestia alone, and Hestia + RVD at both 30 and 90 days. Adding RVD minimally improved predictive accuracy.

Antiphospholipid syndrome (APS), a disorder characterized by the presence of antiphospholipid antibodies, is commonly associated with thrombotic events and pregnancy complications. Although cardiac involvement of APS is very common, intracardiac thrombus is rare and easily misdiagnosed. In order to reduce missed diagnosis and misdiagnosis, we investigated the clinical features of APS with intracardiac mass by summarizing 50 cases (1 newly presented case and 49 additional cases collected from PubMed from 1985 to the present). There were 10 males and 40 females, with ages ranging from 8 to 75 years (median age 35.5). Intracardiac masses were distributed in four cardiac chambers. Mass size ranged from a diameter of 0.5 to 7.1 cm. Clinical manifestations were heterogeneous, including dyspnea, fever, hemiparesis, limb ischemia, and other nonspecific symptoms. In 41 cases with available pathology results, 33 cases were confirmed as thrombus, 2 cases as myxoma, 3 cases as non-bacterial endocarditis, 2 cases as fibrous tissue, and 1 case as inflammatory necrosis. Among 41 cases, 18 cases were suspected of primary cardiac tumors preoperatively, while pathological examination revealed none was tumor. APS patients with intracardiac masses are extremely rare, mostly seen in young or middle-aged people, and they present with a variety of clinical manifestations. Most masses disappear following medical treatment. APS can be accompanied by cardiac myxomas. APS should be promptly investigated in young patients presenting with thrombotic events without any underlying risk factors.

Novel antidiabetic drugs, particularly sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, have significantly transformed the management landscape for type 2 diabetes mellitus, cardiovascular diseases, and chronic kidney diseases, owing to their well-established cardiorenal protective effects. Given the shared risk factors and comorbidities, it is relevant to consider the potential risk of venous thromboembolism (VTE) in individuals prescribed these novel antidiabetic medications. This literature review aims to summarize currently available evidence on VTE risk associated with novel antidiabetic drugs, including GLP-1 receptor agonists, dipeptidyl-peptidase IV (DPP-4) inhibitors, and SGLT2 inhibitors. Following a comprehensive search on PubMed using relevant keywords and backward reference searching, we identified 25 publications that directly reported on associations between these medications and VTE risk. Findings from these studies, including seven meta-analyses, reveal inconsistent results: some studies suggest that GLP-1 receptor agonists or DPP-4 inhibitors may be associated with increased risk of VTE, whereas SGLT2 inhibitors do not appear to be associated with VTE and may even be a protective factor. A notable limitation of the existing studies is the significant challenge posed by confounding in observational studies, while the randomized controlled trials (RCTs) often concluded with a limited number of VTE events, if it was studied. Furthermore, all identified studies focused on the risk of primary VTE, leaving an important knowledge gap regarding whether these novel antidiabetic drugs may influence the efficacy or safety of anticoagulants used for preventing VTE recurrence. Addressing these gaps presents an important avenue for future research.

Deep vein thrombosis (DVT) is a preventable yet serious complication among people living with human immunodeficiency virus (PLWH), attributed to hypercoagulability, low CD4+ counts, and antiretroviral therapy. Despite the high burden of human immunodeficiency virus (HIV), data on DVT in this population remain scarce, particularly in high-prevalence regions. This study systematically reviews the prevalence, risk factors, and outcomes of DVT in adults with HIV. Following PRISMA guidelines, we extracted data from 23 studies (180,495 participants) and conducted subgroup analyses based on country, continent, study design, and quality. Heterogeneity and publication bias were assessed statistically. The global DVT prevalence among PLWH was 14%, with Africa reporting the highest prevalence (47%) and Europe the lowest (3%). Kenya exhibited the highest country-specific prevalence (74%), whereas the Netherlands and Denmark had the lowest (2%). Cross-sectional studies reported the highest prevalence (16%). Identified risk factors included hospitalization, opportunistic infections, malignancies, and comorbidities such as hypertension and diabetes. Funnel plot asymmetry indicated potential publication bias and small-study effects. DVT poses a significant health burden among PLWH, particularly in Africa. Given the high prevalence and associated risk factors, integrating DVT prevention and management into HIV care is critical. Targeted interventions should focus on modifiable risk factors and enhanced diagnostic strategies to improve patient outcomes. Future studies should address knowledge gaps and methodological variations to guide better prevention and treatment approaches.