Journal of Thrombosis and Thrombolysis最新文献

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.

Atrial fibrillation (AF) and malignancy share a complex relationship, significantly complicating patient management. Patients with cancer, particularly those with lung, gastrointestinal, genitourinary, and hematologic malignancies, are at increased risk of AF due to cancer-related hypercoagulability, proinflammatory cytokines, and treatment-related factors. This population faces unique thrombotic and bleeding risks, challenging standard management approaches. Anticoagulation is often complicated by drug-drug interactions with cancer therapies and heightened bleeding risks, including thrombocytopenia and coagulopathy. Left atrial appendage occlusion (LAAO) offers an alternative stroke prevention strategy for patients unable to tolerate long-term anticoagulation. By isolating the left atrial appendage, LAAO reduces thromboembolic risk while minimizing bleeding complications. Indications include patients with elevated stroke risk with contraindications to anticoagulation due to nonreversible causes, such as recurrent bleeding or significant drug interactions. Surgical LAAO may also be considered during cardiac surgery in patients with AF and high thromboembolic risk, with previous studies showing reduced risk of thromboembolic complications. Outcomes of LAAO in cancer patients are generally favorable, with studies showing comparable stroke rates, bleeding risks, and mortality to non-cancer populations. However, malignancy-specific complications, such as device-related thrombus, require further investigation. LAAO provides a promising option for stroke prevention in this complex population, but further research is needed to refine patient selection and optimize outcomes.

To explore the possible causal link between stable angina pectoris (SAP) and gastric cancer (GC) through Mendelian randomization analysis. We used data from genome-wide association studies (GWAS) statistical datasets, with SAP and GC screened as relevant instrumental variables for exposure factors, respectively. To evaluate the causal link between SAP and GC, a two-sample bidirectional Mendelian randomization analysis was conducted, leveraging genetic variants as instrumental variables. In addition, effects of horizontal pleiotropy were evaluated using MR-PRESSO and MR-Egger intercept analysis. Sensitivity analysis was performed using Cochran Q test and "leave one out" method. The study showed a significant causal relationship between SAP and GC in the analysis with SAP as the exposure variable (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.69-0.87, p = 0.000027 using inverse variance weighting [IVW]). Sensitivity analysis confirmed the robustness of Mendelian randomization results. In the analysis of GC as an exposure variable, gastric cancer and SAP also showed a significant causal association (OR = 0.87, 95%CI = 0.77-0.98, p = 0.024 using IVW), but sensitivity analysis suggested a significant pleiotropy between instrumental variables (p = 0.0093 using MR-Egger intercept analysis), which cast doubt on the reliability of the study and requires careful interpretation of the results. Existing studies suggest that individuals with SAP may have a lower risk of developing GC. However, the precise causal relationship, particularly regarding whether GC contributes to an increased risk of SAP, remains unclear and warrants further investigation. GC and ischemic heart disease which represented by SAP are both associated with oxidative stress in their pathogenesis. Local tissue-induced mitochondrial autophagy or cellular ferroptosis triggers a systemic response, potentially underlying the negative correlation between GC and SAP. Thus, therapeutic strategies that target the interplay between local tissue and systemic responses in oxidative stress may hold promise for the benefits to patients.

Venous thromboembolism (VTE) remains a major contributor to postoperative morbidity and mortality in patients undergoing lung cancer surgery. This study aims to identify perioperative risk factors associated with VTE development following such procedures. We performed an exhaustive search of PUBMED and EMBASE from inception to November 1, 2023, using terms related to VTE following lung cancer surgery. A random-effects meta-analysis was performed to calculate the pooled incidence and odds ratios (ORs) for risk factors. Of 3,576 screened studies, 13 met eligibility criteria for qualitative synthesis, and 11 studies (53,382 patients) were included in the meta-analysis. The pooled incidence of postoperative VTE was 1.82% (971 cases). Significant risk factors included advanced age (standardized mean difference [SMD] 0.43, 95% CI 0.22-0.63; I² = 59.9%), prolonged surgical duration (SMD 0.58, 95% CI 0.24-0.92; I² = 81.2%), open thoracotomy (OR 1.77, 95% CI 1.50-2.09; I² = 19.9%), TNM stage > 1 (OR = 1.81, 95% CI 1.53-2.13; I² = 39.8%), adenocarcinoma histology (OR = 1.29, 95% CI 1.08-1.53; I² = 1.2%), and major lung resection (OR = 1.51, 95% CI 1.24-1.83; I2 = 0.0%). This study highlights key modifiable and non-modifiable risk factors for postoperative VTE in lung cancer surgery patients. These findings support individualized risk stratification and targeted thromboprophylaxis strategies to improve clinical outcomes.