Journal of Thrombosis and Thrombolysis最新文献

Ischemic stroke is a leading cause of morbidity and mortality worldwide, resulting from a complex interplay between genetic predisposition and environmental exposures. Recent advances have highlighted the importance of epitranscriptomic regulation, particularly N6-methyladenosine (m⁶A) RNA modification, in the pathogenesis of cerebrovascular diseases. Key m⁶A‑related genes, including the demethylases FTO and ALKBH5, the methyltransferase complex components METTL3 and METTL14, and m⁶A readers of the YTH domain family (e.g., YTHDF1, YTHDF2, YTHDC1), have been implicated in processes such as vascular homeostasis, neuroinflammation, and neuronal survival. Emerging evidence suggests that specific genetic variants within these genes (for e.g., FTO rs9939609, FTO rs17817449, ALKBH5 rs12936694, METTL3 rs1139130, and YTHDF/ YTHDC locus polymorphisms) may modulate individual susceptibility to ischemic stroke. In a real-world contexts, lifestyle and environmental exposures such as diet, smoking, physical activity, and air pollution may interact with these genetic factors, potentially modifying overall stroke risk. This is the first review to systematically highlight m6A-related genes as key interfaces linking genetic susceptibility with environmental exposures in ischemic stroke, emphasizing their potential role as dynamic environmental sensors translating exposure signals into transcriptional and phenotypic outcomes. Elucidating these complex interactions could inform strategies for stroke prevention and the development of personalized therapeutic approaches.

Hypoattenuated leaflet thickening (HALT), a subclinical form of valve thrombosis, is a common finding after transcatheter aortic valve replacement (TAVR). While anticoagulant therapy has been associated with HALT resolution, the efficacy and safety of this approach remain uncertain. To evaluate the effectiveness and safety of oral anticoagulant (OAC) therapy in resolving HALT after TAVR. A systematic review and meta-analysis was performed in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251045514). Studies including adult TAVR patients with imaging-confirmed HALT treated with anticoagulants were included. Outcomes assessed included HALT resolution, valve dysfunction, and major bleeding. Risk of bias was assessed using the ROBINS-I tool, and certainty of evidence was evaluated via GRADE. Summary estimates were calculated using a random-effects model. Nine observational studies involving 369 patients were included, with a follow-up ranging from 78 to 217.6 days, and ranging from 5 days to 9.6 months of interval between TAVR and imaging. The overall pooled HALT resolution rate in imaging follow-up was 90% (95% CI: 0.84-0.95; I² = 15.0%). Otherwise, when discontinuation of OAC had a recurrence rate of 69% (95% CI: 0.49-0.84, I²=0). The bleeding event proportion was 0.05 (95% CI: 0.01-0.18, I² = 0.0%). Sensitivity analyses excluding influential studies suggest the robustness of findings. Anticoagulant therapy is associated with high rates of HALT resolution and appears superior to antiplatelet therapy. These findings support the role of anticoagulation in selected post-TAVR patients with HALT, though randomized trials are needed to confirm efficacy and assess bleeding risk.

To evaluate the clinical course of patients with AF at high risk for both bleeding and stroke, according to OAC use. Data were analysed from three registries across the Middle East, Europe, and Asia-Pacific regions. The study only included 'high risk' patients with AF and CHA₂DS₂-VASc scores ≥ 2 and HAS-BLED scores ≥ 3, who were divided into two groups based on OAC use: OAC users and OAC non-users. Of the 2,535 patients (41.7% female; mean age 75.4 ± 7.8 years), 80.3% (n = 2,037) received OAC therapy. OAC non‑users showed significantly higher crude 1‑year event rates of all‑cause death (116 [23.3%]), MACE (96 [19.3%]) and major bleeding (31 [6.2%]); after multivariable adjustment, they had higher odds of all‑cause death (adjusted odds ratio (aOR) 2.23, 95% CI 1.65-3.01), MACE (aOR 1.92, 95% CI 1.38-2.64) and major bleeding (aOR 2.38, 95% CI 1.42-3.92) compared to OAC users. Enrolment in a non-European setting was associated with a lower risk of all-cause death (aOR 0.61, 95%CI 0.44-0.85) and MACE (aOR 0.42, 95%CI 0.28-0.62). In patients with AF at high risk of both bleeding and stroke, OAC non-use was associated with higher risk of adverse events and bleeding. Decisions on discontinuation of OACs in this subset of patients with AF should be cautiously made and such patients require careful re-evaluation and follow-up.

Thrombosis presents significant healthcare challenges due to its complex nature. Recent advancements in data-driven mathematical and computational models of blood clot formation offer promising insights. The integration of machine learning (ML) and computational methods in thrombosis research is still in its early stages, but it could leverage the strengths of both approaches. This systematic review followed the PRISMA methodology to assess studies that (i) utilized computational models, (ii) modeled blood clot formation or thrombin generation through the coagulation cascade, and (iii) incorporated ML algorithms. We identified 11 eligible studies that focused on platelet signaling, outcome prediction, thrombin threshold prediction, shear rate prediction, and multiscale modeling. Artificial neural networks and support vector machines were the most commonly used ML models. The hybrid approach combining ML and computational models is still nascent but shows significant promise for advancing thrombosis research. These models offer valuable insights for improving thrombosis diagnosis, prognosis, and treatment, particularly in the context of personalized medicine for hemostatic disorders. The integration of ML with computational models holds great potential for improving thrombosis management, but further research is needed. Future work should focus on enhancing the physiological realism of these models, incorporating patient-specific data, and addressing challenges related to data standardization and clinical implementation. The field is in its early stages but shows promising growth potential and is well positioned to advance precision medicine approaches in thrombosis and hemostatic disorders.

Lung cancer is one of the most common malignancies, characterized by a wide prognosis spectrum, different histological subtypes, and a high mortality rate. Hemostatic system imbalance in patients with lung cancer often leads to increased mortality. Intracellular RNAs that share common miRNA binding sites create a competing endogenous RNA (ceRNA) network that plays an important role in gene expression regulation. The emerging role of ceRNAs in tumor development is increasingly being recognized; however, their connection to hemostatic system imbalance in lung squamous cell carcinoma (LUSC) remains unclear. In this study, RNA-seq data of LUSC and normal tissues were downloaded from the TCGA data portal. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) between LUSC and corresponding paracancerous tissues were analyzed using the DESeq2 package in R statistical software. Hemostasis-related genes linked to coagulation and complement cascades (hsa04610) and platelet activation (hsa04611) pathways were identified using the KEGGREST package. The ceRNA network associated with system hemostasis was constructed using differentially expressed RNAs (DERNAs), including mRNAs, lncRNAs, and miRNAs. The GO and KEGG enrichment analysis of DEmRNAs was conducted using the enrichR package. Hazard ratio (HR) and Kaplan-Meier curve were employed to assess the prognostic value of DERNAs using the survival and survminer packages. A ceRNA network comprising 100 hemostasis-related genes, 5 miRNAs, and 57 lncRNAs was constructed. Of these, 19 hemostasis genes, one miRNA (miR-23-3p), and 6 lncRNAs (LINC01615, LINC00707, LINC00702, FEZF1-AS1, DLX6-AS1, CLRN1-AS1) were significantly associated with prognosis in LUSC. Based on correlation analysis, MEF2C-AS1/miR-429/F8, RAP1A, GNAI2, C3AR1, F13A1, P2RY12, LCP2, C1QC axis and CASC11, CASC9, PVT1, BBOX1-AS1/ miR-23b-3p/ PLAU axis may represent key pathways involved in hemostatic system imbalance and the pathogenesis of LUSC. Our analysis revealed a complex ceRNA network associated with system hemostasis and the prognosis of LUSC. These findings may contribute to the development of personalized therapies and valuable prognostic biomarkers for LUSC patients.

Amyloid microclots have been implicated in thrombotic complications across various pathological conditions such as Long COVID symptoms, yet their resistance to enzymatic fibrinolysis causes a therapeutic challenge. In this study we examine the effects of three fibrinolytic enzymes rtPA, Lumbrokinase, and Nattokinase on plasma-derived amyloid microclots, in combination with ultrasound-induced microstreaming and microbubbles. A lab-on-chip platform was used to expose the clots to ultrasound at 150, 300, and 500 kHz. Quantitative analysis revealed that ultrasound alone significantly disrupted clot structures, particularly at 150 kHz, where mean clot diameter was reduced by over 60% and large-clot count (> 30 μm) dropped by more than 80% compared to controls. The addition of fibrinolytic enzymes, however, did not produce statistically significant effects at 150-300 kHz which indicates that mechanical forces were the dominant contributors to clot disruption. At 500 kHz, where ultrasound alone was less effective, enzymatic treatment moderately enhanced the reduction in large-clot burden. These results show the potential of low-frequency ultrasound as a primary method of amyloid microclot breakdown, with enzyme co-treatment offering limited but measurable effect.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by complement-mediated hemolysis and a high thrombotic risk. The introduction of complement inhibitors has markedly reduced thromboembolic events. Eculizumab, the first approved C5 inhibitor, requires biweekly infusions, while ravulizumab, with a prolonged half-life, allows administration every eight weeks. To compare their effects on coagulation dynamics, we retrospectively analyzed paired plasma samples from nine PNH patients sequentially treated with both agents using the Thrombin Generation Assay TGA. TGA parameters were largely comparable between treatments, with a significantly shorter start-tail time observed during ravulizumab therapy (p = 0.04). This data indicating a shorter duration of thrombin generation is consistent with the known more sustained complement inhibition during ravulizumab. No significant differences were found in hemolysis markers, PNH clone size, or blood counts. Despite the small sample size and retrospective design, this study provides the first evidence that ravulizumab and eculizumab exert similar effects on thrombin generation, supporting the equivalent efficacy of long-acting C5 inhibition in maintaining hemostatic balance in PNH.

Clinical practice guidelines on the optimal thromboprophylaxis duration following total hip and knee arthroplasty (THA and TKA) and hip fracture surgery are inconsistent. The aim of this meta-analysis is to investigate the effect of pharmacological prophylaxis duration on postoperative venous thromboembolism (VTE) in these patients. The primary outcome was the incidence of symptomatic and confirmed VTE at three months following surgery. A systematic search was performed in MEDLINE Complete (EBSCO), Embase, CINAHL complete (EBSCO), Web of Science and in CENTRAL databases, for randomised controlled trials comparing extended (minimum 28 days for THA and 10 days for TKA) vs. shorter duration thromboprophylaxis or placebo following these operations. Fifteen trials with a total of 26,580 participants were identified. Compared to shorter prophylaxis, extended thromboprophylaxis reduced 90-day symptomatic and confirmed VTE (OR: 0.43; 95% CI: 0.26-0.72; P = 0.001, I² = 0%; P = 0.75, respectively), significant only in the THA subgroup (P = 0.002). Beneficial effects were also observed with 30-day deep venous thrombosis (DVT) (OR: 0.32; 95% CI: 0.20-0.50; P < 0.001) and proximal DVT incidence (OR: 0.22; 95% CI: 0.12-0.41; P < 0.001) following THA. There were insufficient data to support extended prophylaxis for hip fracture surgery or TKA. Extending thromboprophylaxis up to 25-35 days appeared to reduce the incidence of 90-day symptomatic and confirmed VTE, particularly after THA. However, contemporary perioperative protocols, including early mobilisation and risk stratification, must be considered in determining optimal prophylaxis duration.