Thrombosis Journal最新文献

Objective: This study aims to investigate the effects of gardenia extract (GE) on coagulation function in a rat model of acute myocardial ischemia (AMI).

Methods: Healthy male SD rats were randomly divided into five groups: Sham, AMI, GE-L (low-dose GE), GE-M (medium-dose GE), and GE-H (high-dose GE). Two weeks later, echocardiography was performed to assess cardiac function, including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD). Hematoxylin-eosin (HE) staining and TUNEL staining were implemented to observe myocardial pathological changes and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of inflammatory factors and oxidative stress markers. Coagulation function was evaluated using an automatic coagulation analyzer, with parameters including prothrombin time (PT), thrombin time (TT), prothrombin time ratio (PTR), international normalized ratio (INR), and fibrinogen level (FIB).

Results: Compared with the Sham group, the AMI group exhibited myocardial injury, coagulation dysfunction, impaired cardiac function, and significantly increased levels of inflammation, oxidative stress, and PTR. In contrast, all GE dose groups showed elevated TT, PT, FIB, and INR compared to the AMI group.

Conclusion: GE can reverse the cardiac function, inflammatory and oxidative stress indicators, as well as coagulation function in AMI model rats, thereby improving AMI.

Background: While anti-Xa assays are increasingly used to monitor rivaroxaban therapy, evidence supporting specific thresholds for bleeding risk remains limited.

Objective: To determine predictive thresholds of peak and trough anti-Xa levels for bleeding complications in patients with nonvalvular atrial fibrillation (NVAF) receiving rivaroxaban.

Methods: In this prospective multicenter cohort study conducted at four tertiary care hospitals in Damascus, Syria, we enrolled 70 NVAF patients receiving rivaroxaban (20 mg/day; 15 mg/day if eGFR < 50 mL/min). Anti-Xa levels were measured at peak (1-3 h post-dose) and trough (pre-dose). Patients were followed for 6 months for bleeding events.

Results: Twenty-five patients (35.7%) experienced bleeding (8 major, 17 minor). Bleeding patients demonstrated significantly higher anti-Xa levels (peak: 399 ± 78 vs. 206 ± 67 ng/mL, p < 0.0001; trough: 41 ± 14 vs. 20 ± 10 ng/mL, p < 0.0001). ROC analysis identified optimal predictive thresholds of 298 ng/mL for peak levels (AUC = 0.985, sensitivity 89.5%, specificity 93.3%) and 27.5 ng/mL for trough levels (AUC = 0.887, sensitivity 86.4%, specificity 76.3%).

Conclusion: Anti-Xa levels strongly predict bleeding risk in rivaroxaban-treated NVAF patients. The identified thresholds may guide clinical decision-making regarding dose adjustment, particularly in high-risk patients. However, it is important to acknowledge limitations, including the modest sample size and the exclusion of patients on antiplatelet therapy, which may affect generalizability.

Background: Venous thromboembolism (VTE), which includes Pulmonary embolism (PE) and Deep vein thrombosis (DVT), is a complex vascular disorder with poorly understood pathological mechanisms. Emerging research highlights the potential involvement of immune cells in the pathogenesis of VTE, although their causal relationship remains unproven.

Methods: To systematically assess the causal relationships between 731 immune phenotypic traits and VTE, PE, and DVT, this study employed a bidirectional, two-sample Mendelian randomization (MR) approach. In the forward MR analysis, immune cell characteristics were treated as the exposure, while VTE, DVT, and PE were the outcomes. In the reverse MR analysis, VTE, DVT, and PE were considered exposures, with immune cell characteristics as the outcomes. To ensure the robustness, heterogeneity, and control for potential confounding factors in the study results, we performed a sensitivity analysis. Furthermore, we applied the False discovery rate (FDR) method to account for statistical bias arising from multiple comparisons.

Results: After FDR correction, we identified potential causal associations between four immune cell types and VTE, six types and PE, and three types and DVT.

Conclusion: This study demonstrates that specific immune cell types are causally linked to VTE, DVT, and PE, providing valuable insights for future clinical research.

Background: Antiphospholipid antibodies (aPLs) are detected in 1-5% of the general population. They include lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI). APL increases thrombotic risk, but the pathogenesis of this effect is not fully understood.

Objectives: The aim of this study was to evaluate oxidative and nitrosative stress biomarkers and their relation to certain rotational thromboelastometry (ROTEM) parameters as a risk factor for thrombosis in 32 patients in whom the presence of antiphospholipid antibodies was confirmed, but who had never experienced a thrombosis event (Group 1) in order to rule out any impact of thrombosis on stress parameters. The parameters were also assessed in a group of 23 healthy volunteers (Group 2).

Methods: To assess FRAP and thiol groups we used colorimetric method. The level of protein carbonylation, total pool of 3-nitrotyrosine in plasma proteins, 3-nitrotyrosine-containing fibrinogen as well as the acetyl-lysine-containing fibrinogen were estimated by ELISA. Lipid hydroperoxides were detected using the ferric-xylenol orange hydroperoxide assay. Additionally four ROTEM tests, i.e. INTEM, EXTEM, FIBTEM and APTEM, were performed. In statistical analysis the Mann-Whitney U-test, Student's t-test and logistic regression were used.

Results: TBARS (p = 0,002), LOOH (p = 0,035) and carbonyl groups (p = 0,018) were markedly higher in Group 1 compared to Group 2. Also the acetyl-lysine-containing fibrinogen were significantly higher in Group 1 (p = 0,0028). Other biomarkers did not differ markedly between the studied groups. The obtained results of ROTEM, were not consistent and did not clearly indicate hypercoagulable state.

Conclusion: Study confirms increased levels of oxidative biomarkers in patients in whom the presence of antiphospholipid antibodies was confirmed, but who had never experienced a thrombosis event. Oxidative stress may an important role in the pathogenesis of APS and is not secondary to thrombosis.

Protein disulfide isomerase (PDI) catalyzes the reduction, oxidation, and isomerization of disulfide bonds. Although initially discovered as an endoplasmic reticulum (ER)-residing protein, PDI has been demonstrated to play critical roles on cell surfaces and in the extracellular milieu under different pathophysiological settings. During thrombosis extracellular PDI regulates both platelet activation and coagulation, while during vascular injury PDI modulates proinflammatory neutrophil recruitment and the homeostasis of vascular cells. The identification of PDI substrates using mass spectrometry-based techniques such as mechanism-based kinetic trapping and differential cysteine alkylation has significantly advanced our understanding of the mechanisms whereby extracellular PDI regulates these pathophysiological processes. PDI may reduce or oxidize allosteric disulfide bonds and change the function of adhesive receptors, coagulation-related plasma proteins and signaling molecules that are important during thrombosis and vascular injury responses. The catalytic cysteines of PDI can also be post-translationally modified to enable PDI to transmit redox active species. This review aims to summarize the most recent advances about the roles of extracellular PDI in thrombosis and vascular injury and their mechanisms. With the discovery of novel PDI inhibitors, this body of knowledge will provide novel opportunities to develop strategies for the treatment of thrombotic and vascular diseases.

Objective: The link between venous thromboembolism (VTE) and coronavirus disease 2019 (COVID-19) infection has been consolidated by many studies in the literature. The increased risk of VTE among COVID-19 patients, on the one hand, and the morbidity that can be associated with the ICU course, on the other hand, promote quality care among this patient population. "Choosing wisely" is a quality improvement initiative that emphasizes the importance of assessing the utility of diagnostic tests. Our study was a "Choosing Wisely" single-center initiative aimed at assessing the utility of LEUS among COVID-19 patients who are treated at AUBMC, a major referral center in the Middle East.

Methods: Data from hospitalized COVID-19 patients who underwent LEUS during the pandemic between 2019 and 2021 at our institution were retrospectively analyzed. LEUS was ordered to screen for preexisting DVT prior to the application of mechanical DVT prophylaxis via a serial compression device (SCD) or to rule out suspected DVT. Data on patients' demographics, comorbidities, and mortality were also retrieved.

Results: A total of 179 patients were included in this study. The mean age of the patients was 66.09 ± 16.587 years, and 108 (60.3%) of our patients were men. Ninety-four (52.5%) patients underwent LEUS for asymptomatic DVT screening prior to SCD placement, and 84 (46.9%) patients underwent LEUS to rule out suspected DVT in the context of other causes, namely, prolonged hospital stay, immobilization, and other hypercoagulable risk factors. Among the 94 patients who underwent LEUS screening, 12 (12.76%) patients were found to have DVT, and SCD placement was consequently aborted. Half of these patients had an IVC filter placed afterward. A previous history of DVT or pulmonary embolism (PE) was strongly associated with DVT occurrence in ICU and non-ICU patients. The mortality rate was 88 (49.2%) among the studied population, which was the highest among the ICU patients (88 (69.8%) with p < 0.001).

Conclusion: Compared with the available literature, we report a greater incidence of asymptomatic DVT among COVID-19 patients, including those screened prior to SCD. We suggest that the clinical utility of LEUS for this patient population outweighs its cost and presumed low benefit. Prospective studies with larger sample sizes are needed to further assess the utility of LEUS and promote the "Choosing Wisely" initiative.

Background: Thrombosis is a major pediatric health problem with a spectrum of etiologies, clinical presentations, and morbidities. Establishing the diagnosis and treatment of pediatric thrombosis with different site-related presentations may be challenging. This article adapts the high-quality Clinical Practice Guidelines (CPGs) for pediatric thrombosis management to suit the Egyptian healthcare context.

Methods: The adapted ADAPTE methodology was used to identify the high-quality CPGs published between 2012 and 2023. An expert panel screened, reviewed, and assessed the CPGs and formulated the adapted consensus recommendations based on the best available evidence.

Results: The final CPG document provides consensus recommendations and implementation tools for managing thrombosis with different etiologies in children and adolescents in Egypt. There is no evidence to support strong recommendations for various management approaches.

Conclusions: In general, a complete clinical and radiological assessment and some laboratory tests are indicated at the initial diagnosis to confirm a thrombotic disorder and to further choose the type of workup required. Future research should report the outcome of this adapted guideline and include cost-analysis evaluations.

Background: Pancreatic ductal adenocarcinoma (PDAC) carries a high risk of venous thromboembolism (VTE), which significantly contributes to mortality. However, national trends in VTE-related deaths among this population remain poorly defined.

Methods: We conducted a cross-sectional analysis of U.S. mortality data from 1999 to 2020 using the CDC WONDER platform. Deaths were included if VTE was the underlying cause and pancreatic cancer a contributing cause. Age-adjusted mortality rates (AAMRs) were calculated, and Joinpoint regression was used to assess temporal trends, with subgroup analyses by sex, race/ethnicity, age, region, urbanization level, and place of death.

Results: A total of 20,373 VTE-related deaths occurred in pancreatic cancer patients. The overall AAMR was 0.36 per 100,000 population. A significant increase in mortality was observed, particularly from 2016 to 2020 (APC: 8.71%; p = 0.0039). Males had a higher AAMR than females (0.46 vs. 0.35). Black individuals experienced the highest mortality rate (0.62), followed by White (0.40) and Hispanic (0.36) populations. The burden increased sharply with age, peaking in the 75-84 age group (1.67). Geographic variation was notable, with the Midwest and West showing the highest AAMRs. Urban-rural differences were minimal, though trends rose in both settings. One-third (31.4%) of deaths occurred at home, highlighting potential gaps in outpatient management and end-of-life care.

Conclusion: VTE-related mortality in pancreatic cancer is rising, with disproportionate effects on older adults, males, and Black individuals. These findings highlight the need for tailored prevention strategies, equitable care access, and better integration of palliative services.

Background: Recent studies have shown a relation between red blood cell distribution width (RDW) / albumin (RAR) levels and worse outcomes in cases of pulmonary embolism (PE). Simplified pulmonary embolism severity index (sPESI) has been developed from more complex PESI score, predicting the risk of death in patients with acute PE (APE). This study aims to investigate whether RDW-Standard Deviation/Albumin (RDW-SD/Alb) can serve as a useful prognostic marker for APE and enhance the predictive capability of the sPESI.

Methods: This research is a single-center, retrospective analysis involving patients over 18 years. We enrolled 235 consecutive hospitalized patients with confirmed APE diagnoses. To evaluate the sensitivity and specificity of RDW-SD/Alb, sPESI, and the combined sPESI plus RDW-SD/Alb in predicting 6-month all-cause death, we used Receiver Operating Characteristic (ROC) curves. Additionally, we conducted Kaplan-Meier analysis to assess the impact of elevated RDW-SD/Alb levels (> 13.6) on patient survival time. We utilized multivariate Cox regression analysis to identify independent prognostic factors affecting patients survival.

Results: The mortality rate for RDW-SD/Alb > 13.6 group was significantly higher than that for the RDW-SD/Alb ≤ 13.6 group. Area under ROC (AUROC) of sPESI plus RDW-SD/Alb was statistically larger than AUROC of sPESI (p = 0.025). In the fully adjusted model, increased RDW-SD/Alb levels were consistently linked to all-cause mortality within six months of admission.

Conclusions: The predictive value of the sPESI for 6-month all-cause death improved when the RDW-SD/Alb > 13.6 parameter was included. RDW-SD/Alb, a novel inflammatory marker, was an independent prognostic factor for predicting 6-month all-cause mortality in patients with APE.

Background: The mechanism of thrombotic complications in patients with aortic stenosis (AS) is unclear so far. Our aim was to evaluate the levels of phosphatidylserine (PS) exposed on blood cells, endothelial cells (ECs), and extracellular vesicles (EVs) and its procoagulant activity (PCA) in mild to severe AS patients.

Methods: Exposed PS on blood cells, ECs and EVs were analyzed by flow cytometry. PCA was evaluated by clotting time (CT), intrinsic factor Xa (FXa), extrinsic FXa, thrombin and fibrin formation assays. We also evaluated the inhibitory effects of lactadherin (Lact) on PCA in AS patients.

Results: Our results demonstrated that patients with AS had significantly higher percentages of positive phosphatidylserine (PS⁺) red blood cells (RBCs), platelets (PLTs), white blood cells (WBCs) and ECs compared to controls. Total EVs with PS⁺, platelet EVs (PEVs), endothelial-derived EVs (EEVs) and positive tissue factor EVs (TF⁺EVs) levels were significantly higher in mild to severe AS. In addition, we further confirmed that PS⁺ blood cells, ECs and EVs significantly contributed to shortened CT and dramatically increased FXa, thrombin and final fibrin generation in mild to severe AS compared to controls. Furthermore, lactadherin significantly inhibited the PCA of PS exposure on blood cells, ECs and EVs in AS patients, whereas anti-TF had no this effect.

Conclusion: Our study revealed a previously unrecognized association between exposed PS levels on blood cells, ECs and EVs and PCA in AS. Lactadherin promises to be a new therapy by blocking PS to prevent thrombosis in AS patients.