Journal Of Thrombosis And Thrombolysis[JOURNAL]
Sun
200 papers
Multi target effects of Allium macrostemon against myocardial infarction: an integrated network pharmacology, molecular docking, and experimental study.
He Y, Jiang Y, Leng M … +2 more , Wu F, Ye Z
J Thromb Thrombolysis · 2026 Jul · PMID 42397505 · Publisher ↗
BACKGROUND: Myocardial infarction (MI), a leading cause of global mortality, is inadequately managed by current therapies due to incomplete efficacy and adverse effects. This study aimed to investigate the multi-target m...
BACKGROUND: Myocardial infarction (MI), a leading cause of global mortality, is inadequately managed by current therapies due to incomplete efficacy and adverse effects. This study aimed to investigate the multi-target mechanisms of Allium macrostemon Bunge (AM) against MI using an integrative strategy. METHODS: Bioactive compounds and MI‑related targets of AM were predicted via network pharmacology and validated by molecular docking. The chemical profile of the AM water decoction was characterized by liquid chromatography‑tandem mass spectrometry (LC‑MS/MS). A rat MI model was established to evaluate the cardioprotective effects of AM, including infarct size, platelet aggregation, and coagulation parameters (prothrombin time [PT] and activated partial thromboplastin time [APTT]). RESULTS: Network pharmacology identified 11 bioactive compounds and 63 MI-related targets. Molecular docking confirmed strong binding between flavonoids and critical targets. LC‑MS/MS analysis of the AM decoction revealed a complex chemical profile, including the detection of N‑trans‑feruloyltyramine, a known antiplatelet compound, as a key overlapping constituent. AM reduced infarct size, suppressed platelet activation and cardiac injury markers, restored cardiomyocyte integrity, inhibited fibrosis and macrophage infiltration, with high-dose AM comparable to aspirin. Moreover, AM did not prolong PT or APTT, indicating a favorable bleeding risk profile. CONCLUSION: AM alleviates MI through multi‑target regulation of apoptosis and inflammation, and shows antiplatelet efficacy comparable to aspirin under the present experimental conditions, without prolonging PT or APTT.
Comparative effectiveness of figure-of-eight suture and manual compression for femoral venous hemostasis after atrial fibrillation ablation: A grade assessed meta-analysis.
Bacha Z, Javed J, Khan MH … +12 more , Saif H, Sikandar M, Sajjad F, Khalid M, Abbas M, Khan MM, Qasim M, Mansoor A, Yadk A, Yadav I, Haider MU, Aboumoussa I
J Thromb Thrombolysis · 2026 Jul · PMID 42384139 · Publisher ↗
Atrial fibrillation is a common cardiac arrhythmia associated with serious complications such as stroke, heart failure, and mortality. Catheter ablation is frequently used for drug-resistant cases but requires femoral ve...
Atrial fibrillation is a common cardiac arrhythmia associated with serious complications such as stroke, heart failure, and mortality. Catheter ablation is frequently used for drug-resistant cases but requires femoral venous access and anticoagulation, increasing the risk of vascular complications. Manual compression is the standard method for post-ablation hemostasis, though it can be time-consuming and uncomfortable, whereas figure-of-eight sutures have emerged as a potential alternative. To compare safety and procedural outcomes of figure-of-eight sutures versus manual compression for venous hemostasis after ablation. A systematic literature search was conducted across Cochrane Library, PubMed/MEDLINE, Scopus, and Embase up to February 2026 to identify studies comparing figure-of-eight (Fo8) sutures with manual compression for post-ablation femoral venous hemostasis. Randomized controlled trials and observational cohort studies were included. Data extraction and quality assessment were performed independently by two reviewers, with discrepancies resolved by a third reviewer. Statistical analyses and meta-analyses were performed using RevMan software version 5.4. Nine studies with a total of 2,125 patients were analyzed. Figure-of-Eight (Fo8) suturing demonstrated no significant difference compared with manual compression for total, major, or minor vascular access site complications, bleeding, or hematoma. However, FO8 suturing was associated with significantly shorter time to hemostasis, earlier ambulation, and reduced time to discharge. Figure-of-eight suturing is as safe as manual compression for post-ablation femoral venous hemostasis, showing no increase in vascular access-site complications, bleeding, or hematoma. It provides the added benefit of faster hemostasis, earlier ambulation, and reduced discharge time.
Tissue factor-related biomarkers during combined androgen blockade in patients with prostate cancer: A brief report.
Klampatsas A, Tsiatsiou P, Koutra P … +4 more , Tsakiris DA, Papaioannou M, Skoura L, Dimitriadis G
J Thromb Thrombolysis · 2026 Jul · PMID 42384138 · Publisher ↗
Men undergoing combined androgen blockade therapy (CAB) for prostate cancer are at risk of thromboembolism. Tissue factor (TF) and microparticle-associated tissue factor activity (MP-TF) play a role in coagulation and ma...
Men undergoing combined androgen blockade therapy (CAB) for prostate cancer are at risk of thromboembolism. Tissue factor (TF) and microparticle-associated tissue factor activity (MP-TF) play a role in coagulation and may detect early coagulation changes during hormonal therapy. However, therapy-related hemostatic alterations remain poorly understood. We prospectively studied men with localized and locally advanced prostate cancer treated with CAB through two pathways: radiotherapy (RT) plus CAB (RT + CAB) for localized disease, and radical prostatectomy (RP) followed by adjuvant radiotherapy (ART) and CAB (RP + ART+CAB) for locally advanced disease. We assessed whether TF-related biomarkers were modified during diagnosis and whether this profile remained after 6 months of CAB. We evaluated longitudinal biomarker changes, pathway differences, and their relationship with routine coagulation tests. Circulating TF levels were elevated at baseline and increased after CAB. MP-TF activity remained elevated, with no significant longitudinal change. No significant differences were observed between the treatment pathways (p > 0.05). Routine coagulation parameters remained stable and did not reflect biomarker changes. CAB therapy was associated with increased circulating TF levels and a persistent procoagulant microparticle profile, not reflected by routine coagulation assays. Larger studies with clinical thrombotic endpoints are needed to confirm their clinical relevance.
Opioid use disorder and clinical outcomes following percutaneous coronary intervention for acute coronary syndromes.
Awad A, Hamza M, Smith-Villegas A … +10 more , Tang A, Patel P, Bomma T, Eidy A, Sirekulam V, Akkawi M, Basit J, Ahmed H, Alkatib A, Alraies MC
J Thromb Thrombolysis · 2026 Jun · PMID 42377681 · Publisher ↗
Opioid use disorder (OUD) is increasingly encountered among patients presenting with acute coronary syndromes (ACS), yet its impact on outcomes following percutaneous coronary intervention (PCI) remains unclear. We condu...
Opioid use disorder (OUD) is increasingly encountered among patients presenting with acute coronary syndromes (ACS), yet its impact on outcomes following percutaneous coronary intervention (PCI) remains unclear. We conducted a single-center retrospective cohort study of 5,875 patients undergoing PCI for ACS between 2012 and 2019. Patients were stratified by documented OUD identified using ICD-9 and ICD-10 codes. In-hospital, 30-day, 6-month, and 1-year Outcomes were assessed using multivariable logistic regression, propensity score matching, and time-to-event analyses. Compared with non-OUD patients, those with OUD were more likely to be African American, active smokers, and to have chronic obstructive pulmonary disease, but had lower rates of diabetes. After adjustment, OUD was associated with significantly higher odds of LifeVest prescription during the index hospitalization (adjusted OR 9.94, 95% CI 3.13-31.55). At 30 days, OUD was independently associated with higher risks of any-lesion coronary reintervention (adjusted OR 2.90, 95% CI 1.49-5.66) and same-lesion reintervention (adjusted OR 4.76, 95% CI 1.93-11.77). At 1 year, OUD showed a trend toward higher congestive heart failure readmission (adjusted OR 3.05, 95% CI 0.91-10.28), without significant associations with recurrent ACS or all-cause mortality. Among patients undergoing PCI for ACS, OUD is associated with increased early coronary reintervention and greater likelihood of LifeVest prescription, without increased mortality. These findings highlight a vulnerable population that may benefit from enhanced post-PCI monitoring and multidisciplinary care.
Sex-based differences in clinical outcomes among cardiogenic shock patients treated with mechanical circulatory support.
Olumuyide E, Bae JY, Damrongwatanasuk R … +4 more , Rahman E, Malaga-Espinoza B, Hu JR, Altin SE
J Thromb Thrombolysis · 2026 Jun · PMID 42377680 · Publisher ↗
Despite advances in therapies, cardiogenic shock (CS) remains associated with high mortality rates, often necessitating mechanical circulatory support (MCS) to preserve end-organ perfusion. Despite increasing rates of MC...
Despite advances in therapies, cardiogenic shock (CS) remains associated with high mortality rates, often necessitating mechanical circulatory support (MCS) to preserve end-organ perfusion. Despite increasing rates of MCS utilization, less is known about sex-related differences in clinical outcomes to guide practice. Additionally, standardized management protocols for CS patients requiring MCS that account for sex differences are lacking. In this study, we evaluate sex-specific outcomes in CS patients requiring MCS, examine patterns of MCS utilization by sex, and further stratify clinical outcomes by sex across the overall CS cohort, including the acute myocardial infarction-related CS (AMI-CS), acute heart failure-related CS (AHF-CS), and spontaneous coronary artery dissection-related CS (SCAD-CS) subgroups. We performed a retrospective cohort analysis using the National Inpatient Sample (2016-2020) to identify adult hospitalizations for CS treated with MCS, based on ICD-10 procedure codes. Patients were stratified by sex. Survey-weighted multivariable logistic and linear regression models were employed to assess associations with clinical outcomes. The primary outcome was in-hospital all-cause mortality (ACM). Secondary outcomes included procedural complications, acute kidney injury (AKI), length of stay (LOS), and total hospital charges. Adjusted odds ratios (aOR), 95% confidence intervals (CI), and p-values were reported. Among 161,095 CS patients treated with MCS, 70.2% were male and 29.8% female. Female patients were older (66.0 vs. 63.9 years; p < 0.001) and had significantly higher in-hospital all-cause mortality (32.6% vs. 27.9%; aOR 1.16, 95% CI: 1.09-1.24; p < 0.001). Specifically, female patients had significantly higher in-hospital mortality in both the AMI-CS (30.3% vs. 34.8%; aOR 1.10, 95% CI: 1.03-1.19; p < 0.001) and AHF-CS cohorts (23.2% vs. 25%; aOR 1.12, 95%: 1.02-1.23; p < 0.018). In contrast, no statistically significant sex-based difference in mortality was observed in the SCAD-CS group (30% vs. 28.3%; aOR 1.03, 95% CI 0.64-1.67); p < 0.887). The rates of post-procedural bleeding did not differ significantly between sexes across all causes of CS (4.30% vs. 4.70%; aOR 1.05; 95% 0.92-1.21, p < 0.40). While female patients were at a greater risk of procedural complications (1.5% vs. 0.7%; aOR 1.82, 95% CI: 1.39-2.37; p < 0.001), and cardiac tamponade (3.0% vs. 2.3%; aOR 1.26, 95% CI: 1.06-1.50; p = 0.008), they were less likely to develop AKI (53.2% vs. 60.5%; aOR 0.66, 95% CI: 0.62-0.70; p < 0.001) and less likely to require cardioversion (11.2% vs. 13.1%; aOR 0.83, 95% CI: 0.76-0.90; p < 0.001). Across all forms of mechanical circulatory support (MCS), including ECMO, IABP, and Impella, male patients were consistently more likely to receive MCS compared to female patients. Analysis of temporal trends from 2016 to 2020 revealed no significant changes in MCS utilization patterns between sexes over time. Among patients with cardiogenic shock undergoing MCS, women exhibited higher overall in-hospital mortality and, among AMI-CS and AHF-CS subgroups, had lower healthcare resource utilization. Females demonstrated higher incidence of procedural complication rates, but post-procedural bleeding rates did not differ between the sexes. These findings underscore the importance of incorporating sex-specific considerations into clinical decision-making and management strategies for MCS.
IGF-1 axis: The signalling bond in cancer-associated thrombosis and cachexia?
Pires MM, Tavares V, Ferreira T … +3 more , Silva ACL, de Melo IG, Medeiros R
J Thromb Thrombolysis · 2026 Jun · PMID 42377679 · Publisher ↗
Cancer-associated thrombosis (CAT) and cancer-associated cachexia (CAC) are the most common comorbidities in patients with malignant diseases. Their development is modulated by several factors related to the patient, tum...
Cancer-associated thrombosis (CAT) and cancer-associated cachexia (CAC) are the most common comorbidities in patients with malignant diseases. Their development is modulated by several factors related to the patient, tumour and antineoplastic treatments. Intriguingly, they share a pro-inflammatory setting induced by cytokines released by cancer and host cells in the tumour microenvironment, which leads to metabolic and endocrine derangements across organ systems. The insulin-like growth factor 1 (IGF-1) axis, implicated in metabolism, tissue homeostasis, and tumourigenesis, may play a key role in this interface. Specifically, the dysregulation of the IGF1R-PI3K-Akt-mTOR pathway, which governs protein synthesis (anabolism) and degradation (catabolism), has been involved in muscle wasting associated with CAC. Concerning CAT, while less explored, the roles of the IGF-1 axis in angiogenesis and endothelial stability suggest a potential connection. To address knowledge gaps, this comprehensive narrative review examined the current literature on the IGF-1 pathway's involvement in CAT and CAC, including the implications of genetic markers. As the IGF-1 axis may serve as a signalling bond between these paraneoplastic syndromes, further investigation may lead to the identification of disease predictors, supporting risk stratification and early intervention.
Real-world data on Factor V Leiden in Sweden: A nationwide family study.
Curic E, Pirouzifard M, Sundquist K … +1 more , Zöller B
J Thromb Thrombolysis · 2026 Jun · PMID 42377678 · Publisher ↗
This is the first nationwide real-world register-based family study of factor V Leiden (FVL). To determine number of diagnosed patients with FVL in Sweden and the associated risk for venous thromboembolism (VTE). The Swe...
This is the first nationwide real-world register-based family study of factor V Leiden (FVL). To determine number of diagnosed patients with FVL in Sweden and the associated risk for venous thromboembolism (VTE). The Swedish Multi-Generation Register was linked to the Swedish National patient register for the period 1964-2018. Patients with FVL (FVL heterozygotes or homozygotes) were linked to family members. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for VTE were calculated for individuals with FVL compared with relatives without FVL. Thrombophilia was defined as antiphospholipid antibodies, FVL, prothrombin G20210A mutation, deficiencies of antithrombin, protein C, and protein S. Among 149,808 individuals from 9,641 pedigrees, 11,367 [66.4% females] family members were diagnosed with FVL corresponding to around 0.1% of the Swedish population. Totally 5,757 (59.7%) of the 9,641 index cases (first diagnosed FVL case in pedigree) suffered from VTE, A total of 17,703 (11.8%) family members were affected by VTE. The aHR for VTE for FVL carriers was 9.23 (95%CI 8.92-9.55). After exclusion of 9,641 index cases aHR for VTE was 6.74 (95%CI6.24-7.28). The risk of VTE was dependent on number of thrombophilias present in a patient even after exclusion of index cases. One thrombophilia was associated with an aHR of 7.79 (95%CI7.26-8.36), two thrombophilias 14.71 (95%CI11.10-19.50), and three or more thrombophilias 18.99 (95%CI6.13-58.87). This nationwide real-world register-based family study indicates that FVL is underdiagnosed in Sweden. FVL is a risk factor for VTE in thrombophilic families in Sweden. Thrombophilia screening appears worthwhile.
Robustness and fragility of evidence supporting systemic thrombolysis in acute pulmonary embolism.
Zuin M, Ageno W, Vedovati MC … +3 more , Chopard R, Goldhaber SZ, Simioni P
J Thromb Thrombolysis · 2026 Jun · PMID 42315722 · Publisher ↗
Systemic thrombolysis is recommended for high-risk PE and select intermediate-risk patients. We assessed the robustness of RCT evidence comparing systemic thrombolytic therapy with standard anticoagulation. We systematic...
Systemic thrombolysis is recommended for high-risk PE and select intermediate-risk patients. We assessed the robustness of RCT evidence comparing systemic thrombolytic therapy with standard anticoagulation. We systematically reviewed RCTs of intravenously administered alteplase or tenecteplase versus heparin. The primary endpoint was all-cause mortality; secondary endpoints included recurrent PE, clinical deterioration in intermediate-risk patients, and major bleeding. Fragility index (FI) or reverse FI (RFI) and fragility quotient (FQ) or reverse FQ (RFQ) were calculated to assess outcome stability. Absolute and relative risk reductions, number needed to treat (NNT), and number needed to harm (NNH) were also derived. Nine RCTs enrolling 1,682 patients met inclusion criteria. Overall, systemic thrombolysis was associated with a nonsignificant reduction in mortality (1.7% vs. 3.8%; RR 0.73; 95% CI 0.39-1.38; p = 0.33) with moderate robustness (RFI = 8; RFQ = 0.004; NNT 91; RRR 27%; ARR 2.1%). Mortality was highly fragile in high-risk PE (RFI = 0) and fragile in intermediate-risk patients (RFI = 4). Systemic thrombolysis moderately reduced recurrent PE (RR 0.42; 95% CI 0.18-0.97; FI = 5; RFQ = 0.002) and prevented clinical deterioration in intermediate-risk patients (RR 0.31; 95% CI 0.15-0.65; FI = 8; RFQ = 0.006; NNT 29; RRR 71%; ARR 3.5%). Major bleeding was robustly increased (FI = 30; RFQ = 0.001; NNH 17), mainly driven by tenecteplase (FI = 9; RFQ = 0.007; NNH 11), whereas alteplase showed no significant increase (RFI = 3). Mortality benefit of systemic thrombolysis is fragile, while major bleeding risk is robust, underscoring the limitations of current guidelines and the need for adequately powered RCTs to inform individualized treatment in high- and intermediate-risk PE.
Thromboinflammatory biomarkers and thrombotic risk in virologic failure and drug-resistant HIV: Emerging roles of d-dimer, fibrinogen, and coagulation dysregulation.
Obeagu EI, Okon MB
J Thromb Thrombolysis · 2026 Jun · PMID 42315721 · Publisher ↗
HIV infection that is highly resistant is marked by ongoing viral replication, long-lasting immune activation, endothelial activation, and a prothrombotic condition with heightened risk of thromboembolic complications. E...
HIV infection that is highly resistant is marked by ongoing viral replication, long-lasting immune activation, endothelial activation, and a prothrombotic condition with heightened risk of thromboembolic complications. Elevated D-dimer and fibrinogen remain important indicators of fibrin formation, degradation, inflammation, and coagulation activation in this group. However, contemporary interpretation of these markers should also consider von Willebrand factor (VWF), tissue factor activity, and thrombin generation as mechanistic links between endothelial perturbation and intravascular clot formation. The molecular mechanisms behind these increases entail prolonged endothelial damage, release of VWF from Weibel-Palade bodies, heightened levels of pro-inflammatory cytokines such as IL-6, augmented tissue factor expression on monocytes and endothelial cells, and downstream thrombin generation that converts fibrinogen to fibrin. Simultaneously, fibrinolysis produces D-dimer fragments, acting as sensitive indicators of ongoing thrombogenesis. In individuals with drug-resistant HIV or virologic failure, these mechanisms are heightened, associating biomarker increases with greater risks of venous thromboembolism, cardiovascular events, stroke, and death. Assessing D-dimer and fibrinogen concentrations alongside endothelial and thrombin-generation biomarkers may provide valuable diagnostic and prognostic insight, facilitating early detection of patients with heightened thrombotic risk and guiding prompt clinical actions. Nevertheless, standardized guidelines for biomarker application in HIV-resistant populations remain limited, emphasizing the necessity for additional studies to confirm thresholds, elucidate mechanisms, and enhance management strategies to minimize morbidity and mortality linked to thrombotic complications.
Efficacy and safety of adjuvant tirofiban versus intravenous thrombolysis alone in acute ischemic stroke: an updated meta-analysis of randomized controlled trials.
Leite M, Ribeiro Gonçalves O, de Almeida Monteiro G … +9 more , Marinheiro G, Mutarelli A, Pereira da Silva AM, Andrade Fernandes JV, Pensenstadler K, Singh J, Lee WJ, Pipek L, Mota Telles JP
J Thromb Thrombolysis · 2026 Jun · PMID 42315720 · Publisher ↗
Intravenous thrombolysis (IVT) improves outcomes in acute ischemic stroke (AIS), yet many patients remain disabled. Earlier studies suggested potential benefits of adjunctive tirofiban with smaller samples and pooled het...
Intravenous thrombolysis (IVT) improves outcomes in acute ischemic stroke (AIS), yet many patients remain disabled. Earlier studies suggested potential benefits of adjunctive tirofiban with smaller samples and pooled heterogeneous reperfusion strategies, limiting conclusions about comparison with IVT alone. With new evidence available focused specifically on IVT-treated patients, we conducted an updated meta-analysis with a larger sample comparing tirofiban plus IVT versus IVT alone. We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing tirofiban plus IVT versus IVT alone in AIS. The primary outcome was favorable functional status at 90 days (modified Rankin Scale [mRS] 0-2). Secondary outcomes included excellent recovery (mRS 0-1), moderate-to-severe disability (mRS 3-5), early neurological improvement (NIHSS change at 24 h and 7 days), symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and all-cause mortality. Risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Six RCTs involving 1,793 patients were included. Compared with IVT alone, tirofiban improved favorable functional status (RR 1.14; 95% CI 1.07-1.20) and excellent recovery (RR 1.19; 95% CI 1.09-1.30), while reducing moderate-to-severe disability (RR 0.57; 95% CI 0.44-0.72). NIHSS scores at 7 days favored tirofiban (MD - 2.22; 95% CI - 4.21 to - 0.23), with no difference at 24 h. Safety analyses showed no significant differences in sICH (RR 1.70; 95% CI 0.58-4.97), any ICH (RR 1.17; 95% CI 0.75-1.81), or all-cause mortality (RR 0.98; 95% CI 0.51-1.85). This study provides focused evidence on tirofiban in IVT-treated AIS patients. Our results highlight that adjunctive tirofiban improves 90-day functional outcomes without increasing hemorrhagic or mortality risk. These findings strengthen the rationale for considering the potential role of tirofiban as an adjuvant therapy in IVT and may inform future clinical guidelines.
Machine learning to identify novel bleeding and residual thromboembolic risks in patients on anticoagulation.
Leng X, Yin F, Zhen J … +6 more , Zhu Y, Tong F, Sun W, Li M, Tao Y, Zhang Y
J Thromb Thrombolysis · 2026 Jun · PMID 42301346 · Publisher ↗
Balancing thromboembolic prevention against bleeding risk remains a key challenge during oral anticoagulant (OAC) therapy. CHA₂DS₂-VASc cannot predict residual thromboembolic risk, and HAS-BLED has insufficient predictiv...
Balancing thromboembolic prevention against bleeding risk remains a key challenge during oral anticoagulant (OAC) therapy. CHA₂DS₂-VASc cannot predict residual thromboembolic risk, and HAS-BLED has insufficient predictive ability for direct oral anticoagulants (DOACs).While machine learning offers a transformative paradigm for risk assessment, its clinical application is often hindered by three critical challenges: data imbalance caused by low incidence of embolism and hemorrhage, the omission of drug metabolism-related features, and limited generalizability across diverse DOAC regimens. We retrospectively collected clinical data from patients receiving OAC in the First Affiliated Hospital of Soochow University from 2018 to 2024. To address data imbalance, we recruited patients in case-control manner, then implemented a non-boundary oversampling strategy. To investigate more valuable predictors, we incorporated drug metabolism-related features as potential predictors to develop robust models. Shapley Additive exPlanations (SHAP) analysis supports the global and local interpretation for prediction, validating the contribution of predictors and enhancing the credibility of models in clinic. 281 patients with bleeding events, 213 patients with thromboembolic events, and 978 as negatvie control were recruited. The overall dataset for bleeding risk prediction included 1,259 patients (positive-to-negative ratio ≈ 1:3.48), and that for thromboembolism risk prediction included 1,191 patients (positive-to-negative ratio ≈ 1:4.59). The Light Gradient Boosting Machine (LGBM) achieved an AUC of 0.880 for predicting bleeding risk, outperformed the HAS-BLED score (AUC = 0.730). The Logistic Regression (LR) for predicting thromboembolic risk achieved an AUC of 0.792, outperformed the CHA₂DS₂-VASc score (AUC = 0.628). Decision curve analysis further suggested that these models provided meaningful clinical net benefit within reasonable threshold ranges. SHAP identified pulmonary artery pressure (PAP), left atrial volume index (LAVI), platelet count, and left atrial appendage (LAA) volume as key predictors of thromboembolic risk, while estimated glomerular filtration rate (eGFR), body mass index (BMI), and direct bilirubin were key predictors of bleeding risk, consistent with clinical expectations. By integrating diverse clinical indicators, prioritizing collection of positive events, and applying a new data augmentation, we identified several novel predictors, including PAP, LAVI, platelet count, LAA volume, eGFR, and BMI. Compared with traditional risk scores, the new models suggested superior predictive performance, providing robust evidence-based support for personalized clinical decision-making.
Coagulation at the crossroads: Cancer, congenital disease, and critical illness.
Gorog DA
J Thromb Thrombolysis · 2026 Jun · PMID 42289024 · Publisher ↗
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Advancing cancer therapeutics: new perspectives on mechanisms, regulatory and policy challenges, and innovative multi-modality strategies for the early detection of cardiotoxicity.
Becker RC
J Thromb Thrombolysis · 2026 Jun · PMID 42268506 · Publisher ↗
Recent advances in cancer therapeutics, particularly targeted agents and tissue agnostic immunotherapies, have transformed care while introducing new challenges in cardiovascular safety. Although clinical guidelines have...
Recent advances in cancer therapeutics, particularly targeted agents and tissue agnostic immunotherapies, have transformed care while introducing new challenges in cardiovascular safety. Although clinical guidelines have evolved, regulatory processes critical to ensuring safe innovation remain under-leveraged and often disconnected from real-world implementation. This gap is especially concerning amid federal downsizing, which has led to significant staff reductions at the United States Food and Drug Administration (FDA) and other health agencies. To meet growing needs in patient safety and therapeutic oversight, a new paradigm is emerging-one that is collaborative, adaptive, and inclusive of all stakeholders. Drug manufacturers, oncologists, cardiologists, clinical trialists, regulators, and technology developers must integrate around shared goals. Cardiovascular endpoints should be integrated into pre-new drug application (NDA) studies, with trial designs that include at-risk populations and robust cardiac monitoring. Early detection tools and mitigation strategies should be co-developed when feasible alongside therapeutics and considered part of the approval process.
Long non-coding RNA NPPA-AS1 acts as a potential novel biomarker and promotes atrial fibrillation progression via the miR-302e/TGFBR2 axis.
Li S, Chen N, Wang Q … +2 more , Li B, Fu Y
J Thromb Thrombolysis · 2026 Jun · PMID 42268505 · Publisher ↗
Atrial fibrillation (AF) has complex etiologies. This study aimed to investigate the clinical significance of long non-coding RNA (lncRNA) NPPA-AS1 in AF and the pro-AF mechanism of the NPPA-AS1/miR-302e/transforming gro...
Atrial fibrillation (AF) has complex etiologies. This study aimed to investigate the clinical significance of long non-coding RNA (lncRNA) NPPA-AS1 in AF and the pro-AF mechanism of the NPPA-AS1/miR-302e/transforming growth factor beta receptor 2 (TGFBR2) axis. This study included 120 patients with AF and 120 healthy controls. An in vitro AF model was established by stimulating rat primary cardiac fibroblasts (CFs) with angiotensin II (AngII). RT-qPCR, Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were utilized to assess gene expression, cellular function, and protein concentration, respectively. Molecular target regulation relationships were validated using RNA immunoprecipitation (RIP) and dual luciferase assays. Target genes predicted by multiple databases were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to investigate the biological functions and related signaling pathways of the NPPA-AS1/miR-302e axis. NPPA-AS1 was highly expressed in AF patients, serving as an independent risk factor for AF onset while demonstrating excellent diagnostic efficacy for AF. Its expression may be closely associated with cardiac structural remodeling, myocardial injury, and inflammatory responses in AF patients. Mechanistically, NPPA-AS1 was found to act as a molecular sponge to negatively regulate miR-302e, which directly suppressed TGFBR2 expression, forming the NPPA-AS1/miR-302e/TGFBR2 regulatory axis. In vitro, this regulatory axis was associated with Ang II-induced cellular proliferation, apoptosis imbalance, expression of fibrotic molecules, and inflammatory factor secretion (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6]), suggesting a potential role in AF-related pathological processes. Specifically, interference with NPPA-AS1 reversed these pathological effects, while inhibition of miR-302e counteracted this reversal. Further interference with TGFBR2 could re-block the pathological process. In vitro findings suggest that NPPA-AS1 may amplify AngⅡ-induced atrial fibrosis and inflammation by releasing TGFBR2 inhibition through "sponge-like" adsorption of miR-302e, indicating a potential contributory role in AF pathogenesis.
Verification and optimization of the VTE risk stratification system for multiple myeloma.
Liu Y, Li Q, Guo H … +8 more , Wu Y, Chen Y, Liu Y, Dou X, Peng N, Mo X, Lu J, Wang L
J Thromb Thrombolysis · 2026 Jun · PMID 42268504 · Publisher ↗
Venous thromboembolism (VTE) is a common complication in multiple myeloma (MM), particularly within the first six months of treatment initiation and disease relapse. This study optimized the MM-VTE risk stratification sy...
Venous thromboembolism (VTE) is a common complication in multiple myeloma (MM), particularly within the first six months of treatment initiation and disease relapse. This study optimized the MM-VTE risk stratification system to enable early and accurate identification of VTE risk. We retrospectively analyzed 433 newly diagnosed MM (NDMM) patients from Fu Xing Hospital, Capital Medical University, who were divided into derivation (n = 332) and validation (n = 101) cohorts. Independent risk factors were identified using univariate and multivariate analyses. The optimized MM-VTE risk stratification system was constructed by integrating the identified independent risk factors and thromboprophylaxis status. Model performance was assessed using the area under the curve (AUC). Internal validation was performed with bootstrap resampling, and external validation was conducted using the validation cohort. In the derivation cohort, the 6-month VTE incidence was 8.43% (28/332). Independent risk factors included female sex, bed rest at diagnosis, and platelet count above the upper limit of normal. The optimized MM-VTE risk stratification system was developed by integrating these factors and thromboprophylaxis. The AUC for the IMWG score was 0.605, and the AUCs for the MM-VTE risk stratification system before and after optimization were 0.660 and 0.742, respectively. In the validation cohort, the AUCs of the MM-VTE risk stratification system before and after optimization were 0.659 and 0.730, respectively.The optimized MM-VTE risk stratification system demonstrated improved discriminatory performance in our cohort, offering a potentially more reliable and clinically accessible tool for guiding thromboprophylaxis in Chinese patients.
Early catheter-related thrombosis in oncology patients with central venous access devices: a narrative review of incidence, mechanisms and clinical implications.
Kania J, Zawadzki J, Kudliński B … +1 more , Ziółkowska W
J Thromb Thrombolysis · 2026 Jun · PMID 42240909 · Publisher ↗
Central venous access devices (CVADs) are widely used in oncology patients to facilitate administration of chemotherapy and supportive treatments. However, catheter-related thrombosis (CRT) remains one of the most import...
Central venous access devices (CVADs) are widely used in oncology patients to facilitate administration of chemotherapy and supportive treatments. However, catheter-related thrombosis (CRT) remains one of the most important complications associated with their use. Although overall CRT incidence has been extensively studied, early CRT occurring shortly after catheter implantation remains insufficiently characterized. A narrative review of the literature was performed focusing on studies evaluating CRT in oncology patients with central venous access devices. Relevant studies were identified through searches of the PubMed database and reference lists of selected articles. A total of thirteen studies published between 2005 and 2025 were included in this review. The studies consisted of randomized controlled trials, observational studies, non-randomized studies and retrospective cohort studies, with sample sizes ranging from 48 to 1331 participants. Most studies focused on peripherally inserted central catheters (PICCs), while fewer evaluated centrally inserted central catheters (CICC) or implantable ports. Reported CRT incidence varied widely depending on catheter type, ranging from 3.3% to 61.3% for PICCs, 6.5% to 49% for CICCs and 1% to 7.1% for implantable ports. Early CRT (defined as ≤ 7 days after catheter implantation) was rarely evaluated and was reported in only three studies, with incidence ranging from 2.4% to 48.39%. Across studies assessing thromboprophylaxis, overall CRT incidence ranged from 3.1% to 16.1% in control groups and from 0.4% to 14.1% in intervention groups. CRT remains a clinically relevant complication in oncology patients requiring central venous access. Available evidence suggests substantial variability in thrombosis incidence across catheter types, with generally higher rates observed in PICCs compared with implantable ports. Data on early CRT remain limited and heterogeneous, underscoring the need for prospective studies specifically addressing early thrombotic events following catheter implantation. Improved risk stratification and standardized approaches to prevention and management may enhance clinical outcomes.
Clinical spectrum and mechanistic insights into cardiotoxicity from cancer therapies.
Becker RC
J Thromb Thrombolysis · 2026 Jun · PMID 42228348 · Publisher ↗
Cardiotoxicity is a major concern in oncology, influencing both patient safety and therapeutic decision-making. Part 1 of a dedicated 3-part series provides a comprehensive overview of the fundamentals of cardiotoxicity...
Cardiotoxicity is a major concern in oncology, influencing both patient safety and therapeutic decision-making. Part 1 of a dedicated 3-part series provides a comprehensive overview of the fundamentals of cardiotoxicity associated with cancer therapeutics, beginning with a definition of cardiotoxicity and classifying its mechanisms into direct myocardial injury, indirect cardiovascular effects, and a combination of both. Clinical manifestations are examined across the spectrum of presentations, from asymptomatic cardiac biomarker elevations to overt heart failure, alongside current detection strategies including imaging and patient-reported outcomes. Timing and incidence patterns are analyzed to highlight early versus delayed toxicity and their implications for surveillance strategies used in clinical practice. Guideline-directed therapies are summarized and suggestions for drug development that concomitantly begins to frame cardiotoxic effects are introduced. Lastly, the impact of cardiotoxicity on cancer treatment decisions, including dose modifications, therapy discontinuation, multidisciplinary management, is considered to establish a clear context for optimal patient care.
The COOL-AF 3-year prediction models for death, ischemic stroke, and major bleeding: a report from the COOL-AF registry.
Pumprueg S, Lip GYH, Komoltri C … +2 more , Yindeengam A, Krittayaphong R
J Thromb Thrombolysis · 2026 May · PMID 42218359 · Publisher ↗
Patients with atrial fibrillation (AF) are at increased risk of death, ischemic stroke/systemic embolism (SSE), and major bleeding. Most existing risk models focus on short-term outcomes and are derived mainly from Weste...
Patients with atrial fibrillation (AF) are at increased risk of death, ischemic stroke/systemic embolism (SSE), and major bleeding. Most existing risk models focus on short-term outcomes and are derived mainly from Western populations. We aimed to develop and validate 3-year prediction models for these outcomes in an Asian AF cohort and to compare their performance with established risk scores. We analyzed the 3-year data from the prospective, nationwide COOL-AF registry, enrolling patients with non-valvular AF from 27 hospitals in Thailand. Multivariable Cox proportional hazards models were used to derive prediction models for death, SSE, and major bleeding. Model performance was assessed using discrimination (C-statistics), calibration, and reclassification metrics, and compared with GARFIELD, CHA₂DS₂-VASc, and HAS-BLED models. Among 3,405 patients, 380 deaths, 134 SSE events, and 199 major bleeding events occurred over a median follow-up of 35.9 months. The 3-year COOL-AF models showed good discrimination, with C-statistics of 0.728 (0.712-0.743) for death, 0.703 (0.687-0.718) for SSE, and 0.700 (0.685-0.716) for major bleeding, and demonstrated good calibration. Compared with existing scores, the COOL-AF models performed better than CHA₂DS₂-VASc for death and better than HAS-BLED for major bleeding, while showing comparable or superior performance to the GARFIELD models, particularly for bleeding risk. Reclassification indices further supported the incremental value of the COOL-AF models. In conclusion, the 3-year COOL-AF prediction models provide an acceptable levels of prediction, well-calibrated estimates of death, SSE, and major bleeding in Asian patients with AF and outperform commonly used clinical risk scores, supporting their use for long-term risk stratification and clinical decision-making.
Regulatory challenges and current policy for cardiotoxicity detection in oncology drug development.
Becker RC
J Thromb Thrombolysis · 2026 May · PMID 42213338 · Publisher ↗
The rapid evolution of oncology therapeutics, particularly targeted agents, antibody-drug conjugates, and immunotherapies has outpaced existing regulatory frameworks for detecting and managing cardiotoxicity. Current gap...
The rapid evolution of oncology therapeutics, particularly targeted agents, antibody-drug conjugates, and immunotherapies has outpaced existing regulatory frameworks for detecting and managing cardiotoxicity. Current gaps include inconsistent cardiac safety requirements across development phases, limited incorporation of Cardio-Oncology endpoints within expedited approval pathways, and inadequate harmonization of post-marketing signal detection. These deficiencies underscore the need for a modernized, system-level approach that integrates regulatory science with real-world cardiovascular risk. This review examines approval processes of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), including expedited pathways such as Breakthrough Therapy, Accelerated Approval, PRIority Medicines (PRIME), and upstream activities in pivotal trials. It highlights their strengths in pre-approval drug dose safety and reducing time-to-therapy while critically evaluating limitations in pre-approval cardiac phenotyping, reliance on surrogate endpoints for cardiotoxicity assessment, and constrained post-market surveillance infrastructures that delay informed, patient-centered understanding of safety and efficacy following drug approval.
Bleeding history is associated with lower risk of cardiovascular events in a cohort undergoing lower extremity revascularization.
Bresnahan DJ, Xia Y, Smilowitz NR … +5 more , Luttrell-Williams E, Murphy L, Barrett TJ, Rockman CB, Berger JS
J Thromb Thrombolysis · 2026 May · PMID 42213337 · Publisher ↗
Patients with peripheral artery disease undergoing lower extremity revascularization remain at high risk for cardiovascular events despite intervention. This retrospective analysis of 289 participants examined the relati...
Patients with peripheral artery disease undergoing lower extremity revascularization remain at high risk for cardiovascular events despite intervention. This retrospective analysis of 289 participants examined the relationship between pre-procedural bleeding history and post-procedural outcomes using a modified International Society on Thrombosis and Haemostasis bleeding assessment tool. After median 18-month follow-up, participants with significant bleeding history experienced lower risk of major adverse cardiovascular events (18.4% versus 30.6%, p = 0.034) and mortality (13.6% versus 24.2%, p = 0.047). An inverse exposure-outcome relationship was observed between bleeding severity and outcomes. Bleeding history may identify patients at lower risk for thrombotic complications.
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