Journal of Thrombosis and Thrombolysis最新文献

Hereditary thrombophilia testing is frequently ordered after venous thromboembolism (VTE), despite little evidence of clinical utility and most guidelines cautioning against testing. We conducted a retrospective, observational study of inpatient hereditary thrombophilia testing ordered during a hospital admission for acute VTE between 2019 and 2024. We aimed to characterize patterns of testing results, and costs, and to evaluate whether younger patients and those with unprovoked VTE were more likely to test positive for hereditary thrombophilia. A total of 835 hereditary thrombophilia tests - including those for factor V Leiden, prothrombin_G20210A, deficiencies of protein S, protein C, and antithrombin, hyperhomocysteinemia, and plasminogen activator inhibitor-1 excess - were ordered in 220 patients. Overall, 19.6% of results were abnormal, and 45.0% of patients had at least one abnormal result. There was no difference in the rate of positive results among patients with provoked vs. unprovoked VTE (30.7% vs. 34.5%, p = .554) nor patients < 50 vs. ≥ 50 years of age (33.1% vs. 32.4%, p = .912). Only 4/99 (4.0%) patients with an abnormal result had their clinical management clearly changed due to the result. The tests totaled $385,161 USD in institutional charges and $26,029 USD in Medicare fees. Inpatient hereditary thrombophilia testing during admission for acute VTE is low yield, with frequent abnormal results, many of which likely represented false positives, and minimal impact on clinical management with high costs.

During the alpha wave of SARS-CoV-2 (SCA), the number of ICU-hospitalized COVID-19 patients was high. In a dynamic co-evolution, the virulence of the virus changed during the Omicron wave (SCO). Initial findings of COVID-19 indicate that infection with SARS-CoV-2 leads to endothelial dysfunction through inflammatory pathways, oxidative stress, and alterations in vascular homeostasis. Upregulation of adhesion molecules (ICAM-1 and VCAM-1) in response to pro-inflammatory cytokines helps immune cell migration and vascular inflammation. Furthermore, oxidative stress disrupts the balance between the oxidant and antioxidant systems. Excessive NOX2 activity promotes ROS production and Nrf2 suppression, leading to endothelial dysfunction. Also, alterations in vascular homeostasis and increased vWF secretion heightens the risk of thrombosis, while dysregulated iNOS contributes to further endothelial damage. Considering that endothelial cell dysfunction can promote various disease processes, including thrombosis and atherosclerosis, this study evaluates the main changes in the host lung endothelium in COVID-19 during this co-evolution. The direct effects of SCA and SCO on endothelial function were investigated in bronchoalveolar lavage fluid (BALF) samples obtained from leftover specimens of COVID-19 patients, which were compared to the control group. In the BALF samples of patients, key endothelial molecules involved in immune cell recruitment, such as iNOS, Nrf2, NOX2, vWF, ICAM-1, and VCAM-1, were evaluated using RT-qPCR and Western blotting. In severe COVID-19, ICAM-1 and VCAM-1 were upregulated compared to the control group. Furthermore, vWF expression was also upregulated. A significant increase in iNOS gene expression was observed during the Omicron wave. Although NOX2 expression increased during the SCA and SCO waves, Nrf2 expression was downregulated in both SARS-CoV-2 waves. Overall, during the co-evolution of the virus and host, disruption of endothelial cell function can affect selective immune cell recruitment and, in the late phase, lead to local vascular dysfunction and severe outcomes such as hospitalization. Targeting key endothelial molecules for therapy can not only alter immune cell recruitment but also prevent endothelial dysfunction throughout the body.

Cardioembolic stroke is a major complication of atrial fibrillation (AF). We investigated differentially expressed genes (DEGs) in the left atrial appendage (LAA) with and without LAA thrombus (LAAT) using RNA sequencing (RNA-seq). LAA tissue samples were obtained during cardiac surgery. We analyzed samples with LAAT (n = 6) and without LAAT (n = 5). Differential gene expression analysis was conducted to identify significantly altered genes. RNA-seq identified 27 differentially expressed genes (false discovery rate < 0.05,|log₂(fold change)| >2). Among these, four DEGs-DIRAS3, CYP26B1, PRG4, and ITLN1-exhibited particularly large fold changes. Protein-protein interaction network analysis revealed two hub genes, FKBP5 and TUBA3D, based on degree (≥ 30) and betweenness centrality (≥ 3000). Quantitative PCR confirmed consistent expression patterns for these genes. Furthermore, consistent results were obtained in another independent set (10 cases with LAAT and 10 cases without LAAT). Linear regression analysis, adjusted for age and gender, showed that DIRAS3 expression was significantly associated with both the fibrosis ratio (β = 2.99, 95% confidence interval [CI] 0.22-5.75, p = 0.034) and NT-proBNP levels (β = 373, 95% CI 238-507, p= 5.71E-08). Additionally, CYP26B1 and TUBA3D expression levels were significantly associated with NT-proBNP (β = 349, 95% CI 23.8-674, p= 0.036; β = -140, 95% CI -272 to -8.81, p = 0.038, respectively). We identified candidate genes potentially involved in LAAT in AF patients through RNA-seq analysis. These findings may elucidate the molecular mechanisms underlying LAAT pathogenesis.

In 2011 Luzzatto et al. stated that "Paroxysmal nocturnal hemoglobinuria (PNH) is the most vicious acquired thrombophilic state known in medicine". Fourteen years later, although anti-complement therapy reduced the incidence of thrombotic events, their management remains an unmet clinical need. Historically Vitamin K Antagonists were the first-choice medications for anticoagulation in this setting. Nowadays, Direct Oral Anticoagulants (DOACs) are the standard anticoagulant therapy in most settings due to their predictable pharmacokinetics, fixed dosing, and no need for laboratory monitoring. Poor data is available on their use in paroxysmal nocturnal hemoglobinuria patients in the treatment of the acute-phase of venous thromboembolism (VTE), while no data is available on their use in secondary prophylaxis of VTE. We describe our monocentric experience on the management of thrombotic events in PNH patients and on the use of DOACs as secondary prophylaxis medication. Our retrospective monocentric analysis shows that DOACs could be an effective and safe choice in this setting.

Introduction: Clot waveform analysis (CWA) is a technique that continuously monitors changes in light transmittance or absorbance during fibrin clot formation in plasma, enhancing routine clotting test assessment. Patients with Lupus Anticoagulant (LA) and Hemophilia A (HA) both exhibit isolated prolongation of activated partial thromboplastin time (aPTT); however, their management differs significantly. CWA can aid in distinguishing between these conditions, particularly in cases where standard coagulation tests are inconclusive and specialized assays are unavailable.

Methods: This prospective case-control study included patients with demonstrable LA (n = 69), healthy controls (n = 75) and diseased controls [HA with (n = 16) and without inhibitor (n = 36).

Results: The quantitative data of aPTT-CWA including velocity peak time, acceleration peak time and height of acceleration [-] were significantly lower in LA-positive samples with prolonged aPTT in comparison with HA without inhibitors. The qualitative data comprising Shoulder in 1st derivative, Biphasic wave in 2nd derivative [-] and Serrated wave pattern in 2nd derivative were significantly common in HA samples without inhibitors. In comparison to healthy controls, LA-positive patients with normal aPTT had significantly lower velocity peak time and height of velocity along with higher width of velocity. In acceleration peak time and width of acceleration [-] peak were significantly higher along with lower height of acceleration [+] and height of acceleration [-]. AUROCs of height of acceleration [-], width of acceleration [-] and width of velocity were statistically and biologically significant. The shoulder in 2nd derivative was significantly common in LA-positive samples.

Conclusion: The aPTT-CWA has limited utility for differentiating LA positive from HA samples with and without inhibitors. However, aPTT-CWA may help in selecting patients with normal aPTT who merit further confirmatory testing for LA with a compatible history.

In acute ischemic stroke, the first-pass effect, the occurrence of complete reperfusion after a single pass during endovascular therapy (EVT), is linked to favorable clinical outcomes. This study aimed to investigate the association between thrombus composition and first-pass recanalization (FPR), as well as symptomatic intracranial hemorrhage (sICH), in AIS patients undergoing mechanical thrombectomy (MT). We retrospectively analyzed thrombi retrieved from 172 patients treated with MT. Clots were classified as RBC-rich or platelet-rich. FPR was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b or 3 after a single device pass. Associations with FPR and hemorrhagic outcomes were assessed. A total of 172 patients (91 women, 81 men; mean age 71 years) who were treated with mechanical thrombectomy were included in the study. First-pass recanalization (FPR) was achieved in 55.2% of the patients (95/172). There was no statistically significant relationship between clot composition and FPR (p = 0.991). The rate of intracranial hemorrhage (ICH) was 15.8% in the RBC-dominant group and 1.7% in the fibrin/platelet-dominant group. A statistically significant association was found between clot composition and ICH (p = 0.005), whereas no significant relationship was observed between clot composition and symptomatic intracranial hemorrhage (sICH) (p = 0.975). Successful FPR was associated with a lower rate of sICH (p = 0.003). The percentage of RBCs in clot composition was positively correlated with the presence of the dense artery sign. Gender was not significantly associated with clot composition (p = 0.455), and neither gender nor age showed a significant relationship with FPR (p = 0.316 and p = 0.470, respectively). These findings indicate that while clot composition does not significantly affect the success of FPR, it is significantly associated with the risk of intracranial hemorrhage. This underscores the potential clinical relevance of clot histology in predicting post-thrombectomy outcomes, beyond the well-established importance of FPR itself. Future studies with larger and more diverse patient cohorts are warranted to further elucidate these associations and optimize treatment strategies.

Background: Vitamin K antagonists (VKAs) are the first-line strategy for anticoagulation in patients with left ventricular assist devices (LVADs). Recently, the HeartMate 3 (HM3) LVAD, has shown lower thrombotic complications than previous technologies. Direct oral anticoagulants (DOACs) are emerging as an alternative for oral anticoagulation in this patient cohort. However, their safety and efficacy remain uncertain. As DOACs represent a drug class with differing characteristics, this meta-analysis will examine the influence of the Direct Factor Xa inhibitor Apixaban on HM3-LVAD.

Methods: We systemically searched medical databases for studies comparing Apixaban and VKAs in patients supported with HM3. The primary outcome was hemocompatibility-related adverse events (HRAEs) and major bleeding. All-cause mortality, minor bleeding, all bleeding, thromboembolic events, and stroke were analyzed as secondary outcomes.

Results: Five studies involving a total of 209 patients (119 on Apixaban and 90 on VKAs) were included. The incidence of the primary safety outcome for major bleeding was significantly reduced in the Apixaban group (RR 0.21; 95% CI 0.05-0.81; p = 0.023; I^²=0%). No statistically significant difference was found between Apixaban and VKA group in the analysis of the primary efficacy endpoint of HRAEs (RR 0.59; 95% CI 0.26-1.32; p = 0.204; I^²=0%). All-cause bleeding was also significantly reduced (RR 0.33; 95% CI 0.19-0.57; p = 0.005, I²=0%).

Conclusions: This meta-analysis showed that Apixaban reduced bleeding complications, comparable stroke prevention, and similar survival outcomes. These findings suggest that Factor Xa inhibitors may provide a safer and more patient-friendly alternative to warfarin, particularly in reducing gastrointestinal bleeding and improving anticoagulation management adherence.

Background: Lower extremity deep vein thrombosis (DVT) is a prevalent form of peripheral vascular disease, notable for its high incidence rate. We investigated the potential mechanisms through which the long non-coding RNA (lncRNA) CASC2/miR-152-3p axis regulates the DVT.

Methods: 150 patients diagnosed with DVT and 150 controls were included. CASC2 and miR-152-3p levels were quantified using RT-qPCR. HUVECs viability was assessed via the CCK-8 assay, while cell migration was evaluated using Transwell chamber assays. Flow cytometry was employed to determine cell apoptosis. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), ICAM, and VCAM concentrations were measured through ELISA. The interaction between lncRNA CASC2 and miR-152-3p was validated using a dual-luciferase reporter assay. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for function and pathway enrichment.

Results: LncRNA CASC2 was significantly downregulated in DVT patients. LncRNA CASC2 was independently associated with the occurrence of DVT and demonstrated a relatively high diagnostic value. Overexpression of lncRNA CASC2 significantly enhanced HUVEC's proliferation and migration, while reducing apoptosis and the concentrations of TNF-α, IL-1β, IL-6, ICAM-1, and VCAM-1. Conversely, the knockdown of lncRNA CASC2 resulted in opposite effects. LncRNA CASC2 directly targeted and negatively regulated miR-152-3p. Additionally, miR-152-3p counteracted the effects of lncRNA CASC2 on cell function. GO and KEGG analyses revealed that the target genes of miR-152-3p were mainly involved in the TGF-β and PI3K-Akt signaling pathways.

Conclusion: The lncRNA CASC2/miR-152-3p axis played a critical role in mediating the formation of DVT.

A growing body of evidence points to a strong link between ischemic stroke and the gut microbiome. Given the wide diversity present in gut microbiota, this research intends to employ advanced and thorough data to investigate the causative relationship between gut microbiota and ischemic stroke. We performed a two-sample study using Mendelian randomization to clarify the causal connection between gut microbiota and ischemic stroke. The GISCOME network encompassed 6,021 individuals with ischemic stroke, primarily of European descent. A total of 473 gut microbial taxa were extracted from the genome-wide association study catalog. The research involved a forward Mendelian randomization approach(gut microbiota as exposure, ischemic stroke as outcome). A variety of analytical techniques were applied, including inverse variance weighting, Weighted Median, MR-Egger, Weighted Mode, and Simple Mode. Following this, a sensitivity analysis was performed to confirm the reliability of our findings. Rats underwent treatment using a middle cerebral artery occlusion model, and after 7 days, stool samples were collected for 16s sequencing to assess changes in gut microbiota and to compare these with the Mendelian randomization results. Our analysis suggests a potential causal association between gut microbiota and ischemic stroke. Through forward causal analysis, relationships of causality between 20 different gut microbial taxa and ischemic stroke were unveiled. Findings from 16s sequencing indicated that there was an overlap of 6 gut microbial taxa with the results of Mendelian randomization. The results of our research indicate a direct link between gut microbiota and ischemic stroke, offering possible direction for upcoming clinical trials.

Elevated levels of coagulation factor VIII (FVIII) are more commonly observed in African Americans (AAs) and have been linked to higher risks of thromboembolism and other cardiovascular comorbidities. However, the prognostic implications of elevated FVIII levels in AAs have not been well-studied. We queried the TriNetX (August 2005 to August 2019) to compare AAs with FVIII > 200% to those with 50-200%. A propensity score match (PSM) was used to adjust for potential confounders. Primary outcomes were assessed within five years after the index FVIII and included major adverse cardiovascular events (MACE), while exploratory outcomes included venous thromboembolism (VTE), cerebrovascular events, new-onset heart failure (HF), HF exacerbations, and all-cause mortality. A survival analysis using log-rank tests, Kaplan-Meier curves, and a univariate Cox regression was performed to investigate the association of FVIII with the time to development of each outcome after PSM through the hazard ratio (HR). A multivariate-adjusted analysis was performed before PSM for select outcomes. An E-sensitivity analysis was implemented to assess the association of unmeasured confounders post-PSM. Initially, 11,199 patients were identified from the TriNetX database. After PSM, 3,833 patients with balanced baseline characteristics were included in each cohort. Patients with elevated FVIII had a higher 5-year risk of MACE (HR: 1.14, 95% CI: 1.02-1.27, P = 0.017), VTE (HR: 1.23, 95% CI: 1.11-1.35, P < 0.001), new-onset HF (HR: 1.41, 95% CI: 1.14-1.74, P = 0.001), and mortality (HR: 1.37, 95% CI: 1.20-1.57, P < 0.001). In adjusted models, the association between FVIII and new-onset HF attenuated after accounting for vWF and comorbidities, while the mortality risk remained significant (HR: 1.53, 95% CI: 1.34-1.73, P < 0.001). No significant association was found between FVIII and HF exacerbation. Elevated FVIII levels in AAs are linked to a higher risk of adverse cardiovascular outcomes, including new-onset HF. Future research should explore the dynamic interaction of FVIII with these outcomes, including its potential causal role and its use as a marker for the development of these conditions.