Journal of Thrombosis and Thrombolysis最新文献

This commentary explores the evolving landscape of United States healthcare policy and its global implications, specifically in cardiovascular and thrombosis associated conditions. Recent legislative and executive actions have introduced sweeping reforms to federal programs such as Medicaid, Medicare, and drug pricing (Medicare Drug Price Negotiation, Medicaid Drug Rebate, Federal Supply Schedule) threatening access and affordability for millions of Americans-many already vulnerable and at risk for life threatening and life altering events. These changes reverberate internationally, influencing research collaborations, supply chains, accessibility, and the cost of care. This commentary advocates for evidence-based policy, multi-level collaboration, increased international education directives, and an unwavering commitment to broad-based healthcare access worldwide.

Despite timely primary percutaneous coronary intervention (pPCI), the no-reflow phenomenon (NRP) continues to adversely affect myocardial perfusion and outcomes in ST-segment elevation myocardial infarction (STEMI). While multiple mechanisms are implicated, reliable biomarkers for early prediction remain limited. Platelet-derived growth factor-BB (PDGF-BB), a cytokine involved in vascular inflammation and remodeling, is elevated in acute coronary syndromes. This study aimed to assess whether pre-procedural PDGF-BB levels could predict NRP in STEMI patients undergoing pPCI. In this prospective observational study, 80 STEMI patients undergoing pPCI were grouped by post-procedural TIMI flow: NRP(+) (TIMI ≤2; n=33) and NRP(-) (TIMI 3; n=47). Serum PDGF-BB levels were measured before angiography, and clinical, angiographic, and laboratory variables were compared. PDGF-BB levels were significantly higher in the NRP group (168.5 ± 177.3 vs. 65.5 ± 43.1 pg/mL; p=0.004), along with lower baseline TIMI flow (p=0.002), greater stent diameter (p=0.013), and more total occlusions (p=0.015). PDGF-BB remained an independent predictor in multivariate analysis (p=0.01). ROC analysis showed a cutoff of 89.99 pg/mL predicted NRP with 51.5% sensitivity and 87.2% specificity (AUC=0.688; p=0.004). Elevated pre-procedural PDGF-BB levels are independently associated with NRP in STEMI patients. Although its diagnostic performance is moderate, its high specificity may aid in identifying high-risk patients. Further validation and integration into risk models are warranted.

Cardiac surgery is considered to be a hypercoagulable state with an increased incidence of thromboembolic events. To evaluate the connection between hypercoagulability and mesenteric ischemia (Me-Is), we investigated hemostatic parameters in patients with diagnosed Me-Is. Out of a cohort of 500 consecutive cardiac surgery patients, 25 patients with hyperinflammatory indicators (interleukin-6 > 600 ng/l) and metabolic acidosis (lactate > 4 mmol/l) were retrospectively matched 1:4 into Me-Is (n = 5) and control (n = 20) groups. Blood samples collected before surgery, on intensive care unit (ICU) admission, and 12 h after ICU admission were assessed for hemostatic parameters, including fibrinogen, D-dimer, thrombin-anti-thrombin complex (TAT), and prothrombin fragments 1 + 2 (F1.2). Thrombin generation assays were conducted on all samples, and intestinal fatty acid-binding protein (I-FABP) was assessed as a marker for Me-Is. Baseline levels of hemostatic markers were similar between the two groups. TAT levels were significantly higher in the Me-Is group 12 h after ICU admission (54.20 ± 10.49 vs. 22.18 ± 12.43 ng/ml, p = 0.010). In contrast, at ICU admission, absolute F1.2 values were higher in the control group (1.19 ± 0.04 vs. 0.49 ± 0.47 ng/ml, p = 0.047). However, increase of F1.2 values of the Me-Is group (394.2 ± 231.6%) vs. the control group (114.7 ± 144.9%) 12 h after ICU admission were 3.9- vs. 1.1-fold compared to baseline (p = 0.046). Postoperatively, higher levels of I-FABP and of D-dimers were observed in the Me-Is group at ICU admission (17116.2 ± 18185.4 vs. 2252.3 ± 1582.7 pg/ml; p = 0.006; and 5.3 ± 1.3 vs. 3.0 ± 2.1 µg/ml; p = 0.043; respectively) and 12 h after ICU admission (16998.2 ± 20346.3 vs. 1030.8 ± 1100.0 pg/ml; p = 0.030; and 3.7 ± 1.8 vs. 1.2 ± 0.8 µg/ml; p = 0.005; respectively) compared to the control group. No significant differences were observed for parameters of thrombin generation (TGA, peak value, ETP) between the two groups. Our findings suggest that TAT and F1.2 levels are promising candidates as markers of coagulability after cardiac surgery. High levels of activation markers suggest a temporary stage of hypercoagulability immediately after surgery in Me-Is patients. Nevertheless, the serial assessment of thrombotic profiles offers valuable mechanistic insights, although these exploratory findings require confirmation in larger cohorts.

Following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is standard to reduce thrombotic complications. However, the optimal monotherapy after DAPT remains debated. Clopidogrel may offer better protection than aspirin. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing clopidogrel versus aspirin monotherapy after DAPT in PCI patients. Searches were performed in MEDLINE, Embase, Scopus, CENTRAL, and ClinicalTrials.gov up to April 12, 2025. Outcomes included stroke, myocardial infarction (MI), all-cause mortality, and cardiovascular (CV) death. Hazard ratios (HRs) were pooled using random-effects models. Four RCTs comprising 19,554 patients (clopidogrel: 9,846; aspirin: 9,708) were included. Clopidogrel was associated with a significantly lower risk of stroke (HR: 0.69; 95% CI: 0.51-0.94; p = 0.02; I² = 28%) and MI (HR: 0.71; 95% CI: 0.51-0.99; p = 0.05; I² = 48%) compared with aspirin. There was no significant difference between clopidogrel and aspirin in terms of all-cause mortality (HR: 0.99; 95% CI: 0.78-1.25; p = 0.92; I² = 55%), CV death (HR: 0.87; 95% CI: 0.70-1.08; p = 0.22; I² = 0%), coronary revascularization (HR: 0.95; 95% CI: 0.83-1.09; p = 0.44; I² = 0%), major bleeding (HR: 0.97; 95% CI: 0.70-1.35; p = 0.87; I² = 57%), or stent thrombosis (HR: 0.66; 95% CI: 0.38-1.15; p = 0.15; I² = 0%). Clopidogrel monotherapy post-DAPT after PCI reduces stroke and MI risk compared to aspirin, without increasing mortality or bleeding. These findings support clopidogrel as a favorable alternative for monotherapy.

It is generally accepted that higher phospholipid concentrations generate shorter clotting times. Phospholipid-dependent lupus anticoagulants (LA) assays such as dilute Russell's viper venom time (dRVVT) and silica clotting time (SCT) have therefore been developed. However, cases have been observed where LA confirming tests (concentrated phospholipid) generates longer clotting times than screening tests (diluted phospholipid). This study investigates the underlying cause of this paradox and assess its implications. With different phospholipid concentrations, Russell's viper venom and/or silica-induced clotting times were assayed in normal pooled plasmas (NPPs), factor deficient plasmas, cirrhotic patients' plasmas (CPPs), LA positive plasmas (LPPs). Additionally, routine LA assays were performed in LPPs with or without factor deficiency. In NPPs and factor deficient plasmas, higher phospholipid concentrations resulted in shorter clotting times, however, this effect was more evident with low-middle phospholipid than with higher phospholipid (a U shape curve). In CPPs, clotting time was increasing along with increasing phospholipid from the beginning (right part of a U shape curve). In LPPs, clotting time was shortening along with increasing phospholipid at the beginning, but changeless thereafter (left part of a U shape curve). Compared to LPPs without factor deficiency, LPPs with factor deficiency demonstrated a smaller correction of screening by confirming (dRVVT, 25.9% versus 15.1%, SCT, 28.6% versus 4.1%), leading to a possibility of LA misdiagnosis. Increasing phospholipid could induce "hook effect" in coagulation assays, therefore, phospholipid-dependent clot-based coagulation assays such as LA assays need careful interpretation, especially among patients suffering coagulation factor deficiency.

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.