Thrombosis Journal最新文献

Bleeding diathesis' diagnosis can be challenging due to the high number of disorders with hemorrhagic symptomatology. Sitosterolemia is a rare disease characterized by increased sterols plasma levels and cardiovascular, cutaneous, articular, and hematological manifestations, including anemia and macrothrombocytopenia. The disorder is caused by ABCG5 and ABCG8 mutations.We present a case of a patient with bleeding diathesis, macrothrombocytopenia, a moderate defect of primary hemostasis and a pathological platelet aggregation analysis, with an initial diagnosis of Bernard-Soulier variant syndrome. After performing a genetic study using an exome analysis, the patient had two ABCG8 gen variants, one pathogenic (NP_071882.1:p.Trp536Ter (NM_022437.2:c.1608G > A) variant, ClinVar ID: 499930) and the other one probably pathogenic (NP_071882.1:p.Leu465Arg (NM_022437.2:c.1394T > G) variant), changing the diagnosis to sitosterolemia, which has its own therapeutic approach.This case report shows the importance of the genetic analysis. Sitosterolemia should be suspected in the presence of macrothrombocytopenia, stomatocytes in the blood smear and hemolytic anemia, performing a genetic study including ABCG5 and ABCG8 gene variants.

Background: Angiogenesis inhibitors are vital in cancer treatment but are increasingly linked to thromboembolic events (TEEs), impacting patient outcomes. Despite extensive clinical trials, real-world data on TEEs associated with these agents remain limited. This study examines real-world TEEs patterns using the FDA Adverse Event Reporting System (FAERS).

Method: A retrospective pharmacovigilance analysis was conducted using FAERS data spanning from 2014 to 2024. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) was applied to identify significant safety signals. A signal was considered present when the lower limit of the 95% confidence interval for ROR (ROR025) > 1 and that for information component (IC025) > 0, with a minimum requirement of three or more reported cases.

Results: A total of 13,897 TEEs were identified, with 34.9% classified as arterial thromboembolism events (ATEs), 26.5% as venous thromboembolism events (VTEs), and 38.6% as TEEs of unknown origin (other TEEs). Our findings indicate a significant correlation between the use of angiogenesis inhibitors and an increased reporting frequency of TEEs. The disproportionality analysis revealed strong signals for several agents, with the top five drugs being cediranib, aflibercept, ramucirumab, cabozantinib, and sunitinib. The median time-to-onset (TTO) was 32 days (IQR: 6-141), with 48.5% of cases occurring within the first month and 12% persisting beyond one year. Temporal analysis demonstrated a declining incidence pattern, confirmed by Weibull distribution (shape parameter β = 0.63, indicating early failure type). The most frequently reported outcomes of TEEs associated with angiogenesis inhibitors were hospitalization and other serious events.

Conclusion: This study provides a real-world assessment of TEES risk associated with angiogenesis inhibitors. Identifying high-risk agents and temporal patterns underscores the need for early monitoring and highlights their contribution to TEEs in clinical practice.

Background: Majority of people with "kissing carotids", an anatomical variation of the cervical carotid arteries showing tortuosity, kinking or coiling and coming in proximity at the midline are asymptomatic. Less than 1% of the general population have Protein S Deficiency. This report discusses a rare case of a young female with co-existent Protein S deficiency and kissing carotids, who presented with sequential thrombosis in both arterial and venous cerebral circulation systems and further discusses potential mechanisms of arterial thrombosis in Protein S deficiency and medical options for secondary stroke prophylaxis in this context.

Case presentation: A 29-year-old female presented with sudden left hemiparesis and dysarthria. Index Brain MRI revealed acute non-haemorrhagic infarcts in the right middle cerebral artery (MCA) territory. Index brain MRA of cerebral vessels revealed abrupt cut off of the right MCA M1 segment following arterial thrombosis with extracranial kissing internal carotid arteries. Interval imaging of her brain and cerebral vasculature on day 4 of admission following a convulsion revealed left transverse cerebral venous sinus thrombosis. Laboratory workup confirmed low Protein S activity of only 18% (normal 55-123). She was started on rivaroxaban for lifelong secondary arterial stroke prophylaxis.

Conclusions: This is an index sub-Saharan case report of a young female with co-existent Protein S deficiency and kissing carotids phenomenon presenting with sequential cerebral arterial and venous thromboses. Potential mechanisms of arterial thrombosis in Protein S deficiency in which case warfarin may not be a preferred singular option for secondary arterial stroke prophylaxis are discussed.

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.