Journal Of Thrombosis And Thrombolysis[JOURNAL]
Sun
200 papers
Innovative strategies for early detection of cardiotoxicity: artificial intelligence and multi-modality collaborative models.
Becker RC
J Thromb Thrombolysis · 2026 May · PMID 42213336 · Publisher ↗
Cancer therapeutics account for a significant proportion of new drug development, reflecting advances in diagnosis, treatment, and disease control. However, with this trend comes a responsibility to ensure patient safety...
Cancer therapeutics account for a significant proportion of new drug development, reflecting advances in diagnosis, treatment, and disease control. However, with this trend comes a responsibility to ensure patient safety both in the near term and over the long term. Among these considerations, cardiovascular safety is a priority. Downsizing and resource constraints within regulatory agencies, particularly the United States Food and Drug Administration (FDA) threaten safety oversight capacity, increasing the need for automation, structured data standards, common data elements and shared analytics. Public health policy, public-private partnerships, big data capabilities, and the FDA Oncology Center of Excellence (OCE) provide avenues to strengthen Cardio-Oncology safety through cross-center coordination, technology advances, guidance development, and methodological innovation. In this third offering of a 3-part series, the objective is to outline public-private partnerships and collaborative oversight models, linking sponsors, regulators, health systems, payers, and patient groups to operationalize continuous surveillance, standardized cardiac endpoints, and transparent data sharing. Building on existing scientific and regulatory foundations, there is a pressing need to leverage contemporary technologies and creative, interdisciplinary thinking to advance predictive models, monitoring strategies, and mitigation frameworks. A strategic forecasting and preparedness framework is proposed that includes embedding fit-for-purpose cardiac safety endpoints early in development; interoperable, real-time safety data pipelines across pre- and post-marketing phases; deploying artificial intelligence (AI)-enabled signal detection with human-in-the-loop adjudication; using real world evidence (RWE) to confirm clinical benefit-risk under accelerated approvals; and pre-specifying label-update triggers tied to cardiac signal thresholds. Together, these policy and technology innovations can modernize cardiotoxicity detection, protect patients, and sustain benefits in oncology care.
Patient-centred anti-platelet therapy following coronary artery bypass graft surgery.
De Laurentis E, Sahdev N, Jahangiri M
J Thromb Thrombolysis · 2026 May · PMID 42213335 · Publisher ↗
While lifelong aspirin mono-therapy remains the standard of care following coronary artery bypass graft surgery (CABG), the optimal antiplatelet strategy remains a subject of ongoing debate. The evidence argues against a...
While lifelong aspirin mono-therapy remains the standard of care following coronary artery bypass graft surgery (CABG), the optimal antiplatelet strategy remains a subject of ongoing debate. The evidence argues against a 'one-size-fits-all' strategy and supports a patient-centred approach. Antiplatelet treatment decisions should incorporate bleeding risk which is often multifactorial and necessitates careful individualised evaluation based on patient characteristics and procedural factors. Conduit selection should also be considered as graft failure following CABG remains an important problem and varies according to conduit type, highlighting the critical role of antiplatelet therapy. Saphenous vein grafts are particularly susceptible to early thrombosis and late atherosclerotic degeneration, making optimisation of antiplatelet therapy especially relevant for preserving vein graft patency, whereas its impact on arterial grafts is less well defined. Current guideline recommendations are largely extrapolated from studies involving patients with acute or chronic coronary syndromes treated with percutaneous intervention or medical therapy. Clinical presentation is also a key determinant of antiplatelet strategy. Although current guidelines support resumption of dual antiplatelet therapy (DAPT) after CABG in patients with acute coronary syndromes (ACS), these recommendations are largely inherited from CABG subgroups of broader ACS trials rather than dedicated CABG randomised studies, and recent CABG-specific evidence has challenged the routine use of ticagrelor-based DAPT in this setting. DAPT in chronic coronary syndromes may be considered only in selected patients at low bleeding risk. Although, observational and randomised data suggest that DAPT can improve vein graft patency, but this has not consistently translated into short-term clinical benefit and is offset by increased bleeding risk. In fact, emerging evidence suggests shorter or de-escalated DAPT strategies may offer a more favourable balance between graft protection and bleeding.
Single-cell transcriptomics reveals NDRG1/TGF‑β1 associated vascular smooth muscle cell phenotypic switching in chronic thromboembolic pulmonary hypertension.
Zheng K, Zheng X, Li J … +10 more , Xu M, He B, Liu X, Ma B, Chen J, Miao R, Ye Z, Zhai Z, Liu P, Zhen Y
J Thromb Thrombolysis · 2026 May · PMID 42213334 · Publisher ↗
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a unique combination of mechanical obstruction resulting from organized thrombi and a variable degree of secondary small-vessel remodeling, both o...
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a unique combination of mechanical obstruction resulting from organized thrombi and a variable degree of secondary small-vessel remodeling, both of which contribute to increased pulmonary vascular resistance. In this process, pulmonary artery smooth muscle cell (SMC) phenotypic switching plays a critical role in the progression of microvascular disease. However, the underlying molecular mechanisms remain incompletely elucidated. Single-cell RNA sequencing (scRNA-seq) data from CTEPH patients and normal pulmonary artery tissues (GSE224143, GSE228644) were integrated. After data preprocessing, unsupervised clustering, and cell type annotation using Seurat, we focused on SMC subtype analysis and constructed functional landscapes via pseudobulk DESeq2, Gene Ontology (GO) enrichment analysis, Monocle3 pseudotime trajectory analysis, and high-dimensional weighted gene co-expression network analysis (hdWGCNA). Core findings were validated using bulk RNA-seq datasets (GSE84538) and experimental approaches, including Western blotting, immunofluorescence, EdU proliferation assay, and Transwell/scratch wound healing migration assay. scRNA-seq analysis identified 18 distinct cell clusters in pulmonary vascular tissues. Compared with controls, CTEPH tissues showed reduced fibroblasts and increased immune cells (T cells, monocytes/macrophages) and SMCs. Four SMC phenotypes were identified, with a marked expansion of fibroblast-like SMCs in CTEPH and a dynamic transition from contractile to fibroblast-like phenotype confirmed by pseudotime analysis. Upregulated genes in CTEPH SMCs were enriched in extracellular matrix organization and TGF-β signaling pathways (significantly activated). Cross-validation via hdWGCNA, pseudotime trajectory, and bulk RNA-seq data identified NDRG1 (a hypoxia-inducible gene) as a core gene. NDRG1 was significantly overexpressed in CTEPH SMCs and tissues, positively correlating with pulmonary vascular resistance (PVR). Functional experiments showed that NDRG1 knockdown inhibited hypoxia-induced migration/proliferation of human pulmonary artery smooth muscle cells (HPASMCs), suppressed TGF-β/SMAD pathway activation, and reduced fibroblast-like phenotype marker (Vimentin, COL1A1) expression. NDRG1 is associated with SMC phenotypic switching toward the fibroblast-like phenotype and promotes pulmonary vascular remodeling in CTEPH via the TGF-β/SMAD pathway. NDRG1 and related key gene axes may serve as potential therapeutic targets for CTEPH.
Comparative efficacy and safety of different doses of intravenous thrombolytics in acute ischemic stroke: a GRADE-assessed network meta-analysis of randomized controlled trials.
Sabet H, Abouelmagd ME, Shata A … +6 more , El-Moslemani M, Kadi D, Abo-Elnour DE, Abbas A, Kadirvel R, Ghozy S
J Thromb Thrombolysis · 2026 May · PMID 42213333 · Publisher ↗
To compare the efficacy and safety of different doses of intravenous thrombolytic agents in patients with acute ischemic stroke (AIS) and guide optimal dose selection. We searched PubMed, Scopus, Web of Science, and Coch...
To compare the efficacy and safety of different doses of intravenous thrombolytic agents in patients with acute ischemic stroke (AIS) and guide optimal dose selection. We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL until March 2025 to identify randomized controlled trials (RCTs) evaluating alteplase (tPA), tenecteplase (TNK), reteplase, and recombinant human prourokinase (rhPro-UK) at any dose in patients with AIS. Analysis was performed using R software, and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Primary outcomes included symptomatic intracranial hemorrhage (sICH), 90-day mortality, excellent functional outcome (defined as modified Rankin Scale [mRS] score 0-1), and functional independence (defined as mRS 0-2). We included 21 RCTs (16,643 patients). Compared to tPA (0.9 mg/kg), tPA (0.6 mg/kg) was associated with a significantly lower risk of sICH (RR = 0.48, 95% CI: 0.27-0.86), while TNK (0.4 mg/kg) showed a higher risk (RR = 1.88, 95% CI: 1.06-3.35). No significant differences were observed in 90-day mortality, functional independence, or serious adverse events across interventions. Reteplase (18 + 18 mg) (RR = 1.13, 95% CI: 1.05-1.21) and TNK (0.25 mg/kg) (RR = 1.05, 95% CI: 1.01-1.10) significantly improved 90-day excellent functional recovery compared to tPA (0.9 mg/kg). TNK (0.32 mg/kg) showed the lowest risk probability for any ICH and parenchymal hemorrhage. Some safety outcomes showed dose-dependent effects: lower-dose tPA and intermediate-dose TNK reduced ICH risk compared to higher doses, while mortality and functional independence remained comparable across doses.
Association between cerebrospinal fluid metabolites and ischemic stroke: a Mendelian randomization analysis.
Wei Z, Rong C, Ta Q … +2 more , Wang X, Zhao D
J Thromb Thrombolysis · 2026 May · PMID 42201531 · Publisher ↗
Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. Cerebrospinal fluid (CSF) metabolites can reflect the pathophysiological state of the central nervous system, but their causal rela...
Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. Cerebrospinal fluid (CSF) metabolites can reflect the pathophysiological state of the central nervous system, but their causal relationship with IS remains unclear. This study aims to assess the causal association between CSF metabolites and IS prognosis using Mendelian randomization (MR) methodology. A two-sample MR design was employed, with genetic data on CSF metabolites sourced from the WADRC and WRAP cohorts (a total of 338 metabolites in a European ancestry population), and IS prognosis outcome data obtained from the GISCOME network (6021 IS patients). Single nucleotide polymorphisms (SNPs) significantly associated at P < 5 × 10 were selected as instrumental variables, while those in linkage disequilibrium (r < 0.001) and weak instruments (F < 10) were excluded. Causal estimates were primarily obtained using the inverse variance weighted (IVW) method, with sensitivity analyses conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO, and leave-one-out analysis. Additionally, metabolomic validation was performed using the MetaboLights database (MTBLS6279), ROC curve analysis was conducted to evaluate predictive performance, and KEGG enrichment analysis was undertaken to explore potential mechanisms. The IVW analysis identified 23 CSF metabolites that have a significant causal association with the prognosis of IS. Among these, 18 are protective metabolites (such as sphingolipids, glucuronic acid, N-acetylserotonin, 2'-deoxyuridine, S-adenosylmethionine, cyclic adenosine monophosphate, guanosine, etc.), while 5 are risk metabolites (cholesterol, phenylalanine, erythritol, glutamine, and methionine). Metabolomics validation revealed that 2'-deoxyuridine, S-adenosylmethionine, cyclic adenosine monophosphate, guanosine, and methionine overlapped with the MR results. The ROC curve indicated that deoxyuridine has a high discriminative power (AUC = 0.944, 95% CI: 0.75-1). Sensitivity analysis showed no detected heterogeneity and pleiotropy, and the leave-one-out analysis supported the robustness of the results. KEGG enrichment analysis suggested that the relevant metabolites may be involved in pathways such as autophagy, AMPK signaling, and vascular smooth muscle contraction. This study is the first to systematically evaluate the causal relationship between CSF metabolites and the prognosis of IS, revealing that 23 metabolites may be involved in the occurrence and development of IS. Among these, risk metabolites such as low-density lipoprotein-related cholesterol and phenylalanine are consistent with the mechanisms of atherosclerosis and neuroinflammation. Deoxyuridine, a key intermediate in DNA synthesis and repair, may influence the progression of IS by regulating nucleotide homeostasis and oxidative stress. The MR design effectively avoids confounding and reverse causation bias, while external metabolomics validation and ROC analysis enhance the reliability of the results. This study confirms the causal relationship between various CSF metabolites and the prognosis of IS, with deoxyuridine emerging as a potential biomarker for predicting IS outcomes. These findings provide new insights into the mechanisms of IS and early intervention strategies.
Time- and risk-dependent effects of dual antiplatelet therapy targeting the P2Y12 receptor after CABG: A network meta-analysis of graft permeability and clinical outcomes.
Zhou Y, Zhang X, Gui W … +4 more , Xie J, Chen J, Song Y, Ma R
J Thromb Thrombolysis · 2026 May · PMID 42178455 · Publisher ↗
The optimal anticoagulation strategy following Coronary artery bypass grafting remains undetermined, particularly regarding the balance between graft patency, ischemic events, and bleeding across different follow-up peri...
The optimal anticoagulation strategy following Coronary artery bypass grafting remains undetermined, particularly regarding the balance between graft patency, ischemic events, and bleeding across different follow-up periods and risk profiles. A systematic search was conducted in PubMed, Embase, Web of Science, and the Cochrane Database to identify randomized controlled trials comparing regimens of aspirin, DAPT (clopidogrel or ticagrelor), and rivaroxaban. The primary angiographic endpoints were saphenous vein graft(SVG) patency and the left internal mammary artery(LIMA) occlusion; clinical endpoints included myocardial infarction, major adverse cardiovascular events(MACE), major bleeding, and all-cause mortality. A random-effects network meta-analysis was conducted, reporting odds ratios (OR) and 95% CIs, with pre-specified 1-year follow-up stratification and multiple subgroup analyses.The primary analysis included 17 RCTs with 1-year follow-up (9,831 patients). SVG occlusion: Aspirin plus ticagrelor (OR = 0.41,95% CI:0.30-0.56) and aspirin plus clopidogrel (OR = 0.59, 95% CI: 0.44-0.78) were both significantly superior to aspirin monotherapy. MACE: Compared with aspirin monotherapy, no anticoagulation strategy showed a statistically significant difference. Major bleeding: Aspirin plus ticagrelor (OR = 2.53,95% CI:1.59-4.04) and rivaroxaban monotherapy (OR = 2.33, 95% CI: 1.01-5.37) significantly increased the risk. No strategy showed statistically significant differences in myocardial infarction or all-cause mortality. No clear conclusions could be drawn regarding LIMA occlusion due to the rarity of events. Subgroup analysis: In the subgroups of off-pump CABG (OR = 0.42, 95% CI: 0.19-0.90) and early initiation ≤ 48 h (OR = 0.47, 95% CI: 0.29-0.75), the combination of aspirin and ticagrelor significantly reduced MACE; however, the risk of bleeding increased with this regimen when initiation was delayed (> 48 h) (OR = 2.51, 95% CI: 1.52-4.16). Sensitivity analyses showed that the conclusions regarding SVG occlusion and major bleeding were highly robust (the direction and significance of ORs remained consistent across all sensitivity scenarios), whereas estimates for MACE and all-cause mortality were sensitive to specific studies. The net benefit of post-CABG antithrombotic therapy is time- and patient-specific. DAPT (particularly aspirin plus clopidogrel) offers the optimal balance between revascularization protection and bleeding risk; the ticagrelor regimen provides stronger ischemic protection but comes at a higher cost of bleeding; the rivaroxaban regimen is not suitable for routine use. An individualized antithrombotic strategy based on risk stratification is recommended.
Time-dependent efficacy and safety of endovascular treatment in anterior circulation stroke: A systematic review and meta-analysis.
Santanna RV, Júnior VBS, Schuster TB … +4 more , Bezerra FB, Marques GVR, Rosa MEBV, da Silva VEB
J Thromb Thrombolysis · 2026 May · PMID 42178454 · Publisher ↗
Acute ischemic stroke of the anterior circulation is a leading cause of mortality and disability. Although endovascular treatment combined with medical therapy (EVMT) has demonstrated substantial efficacy, its risk-benef...
Acute ischemic stroke of the anterior circulation is a leading cause of mortality and disability. Although endovascular treatment combined with medical therapy (EVMT) has demonstrated substantial efficacy, its risk-benefit profile across different treatment windows remains uncertain. This meta-analysis aimed to evaluate the impact of time from symptom onset on the efficacy and safety of EVMT compared with best medical therapy (BMT) alone. PubMed, Embase, and the Cochrane Library were searched from inception to June 30, 2025. Randomized clinical trials enrolling adults with anterior circulation acute ischemic stroke assigned to EVMT versus BMT were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models in RevMan version 5.4. The I² statistic was used to measure heterogeneity. Nineteen trials comprising 5,209 patients (2,517 EVMT; 2,692 BMT) were included. EVMT was associated with a reduction in 90-day mortality compared with BMT (OR 0.79; 95% CI 0.67-0.93; P = 0.005), with the strongest effect within ≤ 12 h (OR 0.63; 95% CI 0.46-0.86; P = 0.003). Functional outcomes consistently favored EVMT across all windows (OR 2.44; 95% CI 1.97-3.01; P < 0.0001). EVMT was associated with an overall increased risk of symptomatic intracranial hemorrhage (OR 1.68; 95% CI 1.26-2.23; P = 0.0004), including in the ≤ 12 h, ≤ 24 h, and 6-24 h subgroups, but not within ≤6 h. Treatment effects were significant across time windows, however, with no significant interaction detected. EVMT improves functional outcomes across all evaluated time windows, with a favorable safety profile within 6 h from symptom onset and an |increased hemorrhagic risk with delayed treatment, without evidence of significant effect modification by time.
Systemic immune-inflammation index predicts left atrial thrombus in non-valvular atrial fibrillation: A retrospective study of 847 patients.
Wang Y, Zhou S, Zhang C … +1 more , Zhang H
J Thromb Thrombolysis · 2026 May · PMID 42177746 · Publisher ↗
Non-valvular atrial fibrillation (NVAF) serves as a primary cause of cardioembolic stroke, with left atrial thrombus (LAT) functioning as its major thrombotic substrate. The systemic immune-inflammation index (SII) has g...
Non-valvular atrial fibrillation (NVAF) serves as a primary cause of cardioembolic stroke, with left atrial thrombus (LAT) functioning as its major thrombotic substrate. The systemic immune-inflammation index (SII) has gained recognition as a dependable biomarker in cardiovascular disease. Nevertheless, its relationship with LAT in NVAF patients has not been thoroughly characterized in large-scale investigations. This retrospective study enrolled 847 NVAF patients who underwent transesophageal echocardiography (TEE). The primary outcome was TEE-detected left atrial thrombus (LAT). Patients were stratified into LAT-positive and LAT-negative groups. Univariable and multivariable logistic regression analyses identified independent predictors of LAT. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic performance of SII compared to the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and CHA₂DS₂-VASc score. Restricted cubic spline (RCS) analysis assessed the dose-response relationship between SII and LAT risk, and prespecified subgroup analyses examined whether this association remained consistent according to oral anticoagulant (OAC) use and other clinical strata. Of 847 patients, 142 (16.8%) were LAT-positive. Elevated SII was an independent predictor of LAT (OR = 1.13, 95% CI: 1.08-1.18 per 100-unit increase; P < 0.001) after adjusting for conventional risk factors. The optimal SII cutoff was 712.5 (AUC 0.786), showing slightly better discrimination than NLR, PLR, and CHA₂DS₂-VASc score. RCS analysis revealed a significant nonlinear dose-response relationship between SII and LAT risk, and the association remained consistent in both adequate-OAC and non-OAC subgroups. Elevated SII is independently associated with LAT in NVAF patients and offers useful discriminatory performance as an adjunct, rather than a standalone substitute, for established clinical assessment. As a readily accessible hematological parameter, SII may help identify patients with a low probability of LAT while supporting individualized decisions regarding TEE referral and anticoagulation management.
Temporal Trends and Future Projections of P ulmonary Embolism and Top Contributing Causes of death in the United States, 1968-2040: insights from the CDC WONDER database.
Khan S, Abbas F, Hassan M … +11 more , Hussain M, Ahmed M, Ahsan A, Qureshi S, Khalid N, Sajjad A, Baig M, Waqas SA, Fonarow GC, Greene SJ, Ahmed F
J Thromb Thrombolysis · 2026 May · PMID 42177745 · Publisher ↗
Pulmonary embolism (PE) is a preventable yet often deadly cardiovascular event. We aimed to investigate PE mortality trends from 1968-2023 and forecast rates through 2040 in the U.S. We analyzed CDC WONDER death certific...
Pulmonary embolism (PE) is a preventable yet often deadly cardiovascular event. We aimed to investigate PE mortality trends from 1968-2023 and forecast rates through 2040 in the U.S. We analyzed CDC WONDER death certificates for adults ≥ 25 years. Age-adjusted mortality rates (AAMRs), annual percent changes (APCs) were used to analyse trends and Auto-ARIMA/Prophet forecasting models were used for future projections, all stratified by sex, age, race, and contributing cause of death. From 1968-2023, 516,187 PE deaths occurred, with a mean AAMR of 6.06 per 100,000 (AAPC -1.85). Mean AAMRs were 6.76 in men and 5.57 in women. By age, rates averaged 0.98 for adults 25-44 years, 3.96 for 45-64 years, and 21.73 for ≥ 65 years. Black adults had a mean AAMR of 10.87 versus 5.76 in White adults. From 1999-2023, PE death linked to Coronary Artery Disease, COPD, infection, and diabetes declined, while PE death linked to hypertension rose and heart failure related PE plateaued. Forecasts project an overall AAMR of 3.63 by 2040 (2.32 in men, 3.25 in women), with the highest predicted rate of 9.24 among adults ≥ 65 years. Projected racial AAMRs are 3.70 in White and 7.71 in Black individuals. Hypertension and heart failure linked rates are expected to rise further. Despite a sustained decline in PE death since 1968, persistent racial gaps, aging populations, and rising hypertension and heart-failure related PE threaten progress, highlighting the need for targeted prevention and equitable cardiovascular risk management.
Direct oral anticoagulants versus vitamin K antagonists for atrial fibrillation patients on dialysis: A systematic review and meta-analysis of randomized controlled trials and real-world evidence.
Shaheen O, Hamdy M, Afifi IA … +6 more , Hassan AA, Kassar O, Ismail A, Bedwany SS, Elhalawany BAE, Diab RA
J Thromb Thrombolysis · 2026 May · PMID 42177744 · Publisher ↗
Atrial fibrillation (AF) is the most common arrhythmia in end-stage renal disease (ESRD) patients on dialysis. These patients face high risks of both thromboembolism and bleeding. Pivotal randomized controlled trials (RC...
Atrial fibrillation (AF) is the most common arrhythmia in end-stage renal disease (ESRD) patients on dialysis. These patients face high risks of both thromboembolism and bleeding. Pivotal randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) excluded these patients, leaving the optimal anticoagulant choice uncertain. We conducted a systematic review and meta-analysis investigating the efficacy and safety of DOACs versus VKAs in AF patients undergoing dialysis. We searched PubMed, Scopus, Web of Science, and Cochrane Library for RCTs and observational studies. Primary outcomes were ischemic stroke, major bleeding, and all-cause mortality. Secondary outcomes included ischemic stroke or systemic embolism, other bleeding events, hemorrhagic stroke, myocardial infarction, and cardiovascular mortality. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Four RCTs and nine observational studies were included in this study, encompassing 31,238 patients. DOACs were associated with significantly lower risk of major bleeding (RR: 0.68, 95% CI [0.49-0.95], I = 89.0%), gastrointestinal bleeding (RR: 0.74, 95% CI [0.61-0.90], I = 37.1%), and hemorrhagic stroke (RR: 0.23, 95% CI [0.07-0.78], I = 1.5%) compared to VKAs. Both groups showed similar risk of ischemic stroke (RR: 0.59, 95% CI [0.32-1.09], I = 40.8%), all-cause mortality (RR: 0.85, 95% CI [0.68-1.07], I = 73.2%). Other secondary outcomes also showed no significant differences. In AF patients with ESRD receiving dialysis, DOACs provide similar efficacy and lower bleeding risk compared to VKAs. Among DOACs, apixaban appears to offer the greatest net clinical benefit in this population.
Autologous whole blood clot formation with actigraft in patients receiving oral anticoagulant therapy: an ex vivo feasibility study.
Jacobson BF, Schapkaitz E, Cree MM
J Thromb Thrombolysis · 2026 May · PMID 42177743 · Publisher ↗
The clotting characteristics of autologous whole blood clots for chronic wound management in patients on anticoagulant therapy are not well defined. An exploratory ex vivo study was performed using the ActiGraft autologo...
The clotting characteristics of autologous whole blood clots for chronic wound management in patients on anticoagulant therapy are not well defined. An exploratory ex vivo study was performed using the ActiGraft autologous whole blood clot (RedDress Ltd, Haifa, Israel) in patients receiving oral anticoagulant therapy. Twenty-five participants were eligible for inclusion and stratified into three age-matched cohorts: vitamin K antagonist-warfarin (n = 9), factor Xa inhibitor- rivaroxaban (n = 6), and controls not receiving anticoagulation (n = 10). The primary endpoint was clot formation time. Clot formation time was defined as the time point at which no fluid movement was observed. In the study population (median [interquartile range] age 47 [42-52] years), the mean clot formation time was 10.5 ± 2.6 min (reference:8-12 min). Mean clot formation time was significantly different across groups (p < 0.001). Compared with controls (8.4 ± 1.2 min), clot formation time was significantly prolonged in both the warfarin group (11.3 ± 2.3 min; p < 0.002) and the rivaroxaban group (12.7 ± 2.4 min; p < 0.001), with no significant difference between anticoagulant groups (p = 0.297). Nonetheless, complete, stable clots were consistently formed within the expected time frame in all samples across all groups. This illustrates the feasibility of ActiGraft autologous whole blood clot in patients receiving therapeutic anticoagulation. Further studies are indicated in patients with chronic wounds to assess broader safety and efficacy.
Two decades of pulmonary vascular disease and ischemic heart disease mortality in the united states: A longitudinal analysis using CDC WONDER (1999-2020).
Nawaz A, Hafeezullah F, Siddiqui ZA … +8 more , Faheem MSB, Ahmed N, Zahid R, Zubair A, Muhammad BG, Ibrahim J, Jamil MR, Afridi MK
J Thromb Thrombolysis · 2026 May · PMID 42177742 · Publisher ↗
Pulmonary vascular disease (PVD) and ischemic heart disease (IHD) are major contributors to cardiovascular mortality in U.S. adults. This retrospective study aims to examine mortality trends and demographic disparities b...
Pulmonary vascular disease (PVD) and ischemic heart disease (IHD) are major contributors to cardiovascular mortality in U.S. adults. This retrospective study aims to examine mortality trends and demographic disparities between 1999 and 2020. However, both diseases have been studied individually, but their combined temporal trends remain unexplored. The CDC WONDER database was used to obtain data for adults aged ≥ 45 years. AAMRs per 100,000 population and APC were calculated using Joinpoint regression, stratified by demographic, geographic, and urbanization categories. PVD and IHD together reported a total of 184,780 deaths. The overall AAMR increased from 6.9 to 8.9 per 100,000 between 1999 and 2020. Mortality rates were higher in men (8.8) compared to females (6.0) throughout the study period. Black or African American individuals had the highest AAMR (8.9), demonstrating a current surge in 2018. Similarly, non-metropolitan areas consistently experienced greater AAMR (8.5) than metropolitan areas (6.9), with a steep rise after 2018 (APC = 14.72%). Furthermore, mortality was greatest in the South; however, the Midwest region reported the highest AAMRs (8). Additionally, individuals aged 85 + had the highest CMR (44.6). Lastly, Vermont had the highest AMMRs (13.6) among other states. PVD- and IHD-related mortality depicted a recent steep increase despite an initial decline, with considerable differences across demographic and regional groups. This highlights the importance of a direct call to action by expanding preventive care, spreading awareness, and early diagnosis with management to address these inequities and decrease the growing burden.
A qualitative study of warfarin self-management in the United States healthcare system: insights from patient experiences.
Gilbert SJ, Hong H, Jones AE … +4 more , Vazquez SR, Barnes GD, Sylvester KW, Witt DM
J Thromb Thrombolysis · 2026 May · PMID 42176164 · Full text
Evidence-based guidelines recommend patient self-management (PSM) over other warfarin dosing management methods. Despite this, PSM remains virtually nonexistent in the United States (US) healthcare system. We gathered pe...
Evidence-based guidelines recommend patient self-management (PSM) over other warfarin dosing management methods. Despite this, PSM remains virtually nonexistent in the United States (US) healthcare system. We gathered perspectives and opinions about PSM from patients who participated in a PSM implementation study in three US healthcare systems. Interviews were conducted with patients from three different US healthcare systems. Thematic qualitative analysis informed by the Consolidated Framework for Implementation Research (CFIR) was performed on interview transcripts to explore patient-perceived benefits and challenges of PSM in the US. Fifteen patients participated in individual interviews. Six major themes were identified: (1) Patients found PSM easy and empowering, enhancing their autonomy, responsibility, knowledge, and control over warfarin management; (2) Patients emphasized that trust and support from clinicians was crucial to their confidence and success with PSM; (3) Patients felt PSM should be made widely available; (4) Patients felt they needed more support and training for complex or non-routine situations during PSM; (5) Inflexibility from the healthcare system, clinicians, and PSM processes were common challenges to PSM; (6) Most patients found PSM straightforward and relied on their own judgment, rarely using the provided dosing tools. Patients who participated in a PSM implementation study reported many benefits of PSM. Patients viewed PSM as an empowering approach to warfarin management that enhanced their autonomy and confidence - especially when supported by clinicians. Given the reported advantages of PSM, select patients with sufficient experience and training may benefit from being offered PSM in the US.
Anaemia and long-term outcomes after surgical treatment of uterine fibroids: evidence from real-world data.
Essa H, Hapangama DK, Welters I … +1 more , Lip GYH
J Thromb Thrombolysis · 2026 May · PMID 42176163 · Publisher ↗
Uterine leiomyomas are the most common benign gynaecological tumours and a major cause of heavy menstrual bleeding, frequently resulting in iron deficiency anaemia. However, the long-term cardiovascular and thromboemboli...
Uterine leiomyomas are the most common benign gynaecological tumours and a major cause of heavy menstrual bleeding, frequently resulting in iron deficiency anaemia. However, the long-term cardiovascular and thromboembolic consequences of fibroid-related anaemia remain poorly understood. We conducted a retrospective cohort study using the TriNetX health research network (~ 160 million patients). Women with uterine fibroids undergoing surgical management were identified and stratified by the presence or absence of anaemia within three years before surgery. Propensity score matching (1:1) was applied to balance demographics and comorbidities. Twelve-month outcomes included all-cause mortality, myocardial infarction, stroke, atrial fibrillation/flutter, heart failure, and venous thromboembolism. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. From 83,319 eligible patients, 9,581 anaemic and 9,581 non-anaemic women were well matched. At one year, the presence of anaemia was associated with higher risks of mortality (RR 1.93, 95% CI 1.04-3.60, p = 0.03), stroke (RR 1.65, 1.05-2.60, p = 0.02), atrial fibrillation/flutter (RR 1.60, 1.03-2.48, p = 0.03), heart failure (RR 1.97, 1.43-2.70, p < 0.0001), and venous thromboembolism (RR 2.15, 1.67-2.80, p < 0.0001). No significant difference was observed for myocardial infarction (RR 1.44, 0.80-2.60, p = 0.22). The composite cardiovascular outcome was significantly elevated (HR 1.74, 95% CI 1.44-2.09, p < 0.0001). Preoperative anaemia in women undergoing fibroid surgery independently predicts adverse cardiovascular and thromboembolic events and nearly doubled 12-month mortality. Early recognition and optimisation of anaemia may improve clinical outcomes.
Pulmonary embolism associated with CRBN-targeting immunomodulatory drugs: a FAERS-based pharmacovigilance and mechanistic analysis.
Li B, Xu Y, Liu Y … +3 more , Hu M, Liao S, Tu Y
J Thromb Thrombolysis · 2026 May · PMID 42176162 · Publisher ↗
CRBN-targeting immunomodulatory drugs (IMiDs), including lenalidomide and pomalidomide, are widely used in hematologic malignancies but are associated with an elevated risk of venous thromboembolism (VTE). However, real-...
CRBN-targeting immunomodulatory drugs (IMiDs), including lenalidomide and pomalidomide, are widely used in hematologic malignancies but are associated with an elevated risk of venous thromboembolism (VTE). However, real-world risk patterns and the potential biological mechanisms underlying pulmonary embolism (PE) remain incompletely characterized. We conducted a comprehensive pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) from 2004 to Q3 2025. Disproportionality analyses (ROR, PRR, BCPNN, MGPS) and Weibull distribution modeling were employed to assess signal strength and time-to-onset (TTO). Systems biology tools, including network pharmacology and enrichment analyses (GO, KEGG), were used to uncover shared and drug-specific pathogenic pathways. Bibliometric mapping of core literature further validated mechanistic insights and policy relevance. A total of 2,428 and 372 PE cases were identified for lenalidomide and pomalidomide, respectively. Both drugs exhibited an "early failure" risk profile (β < 1), with a shorter median TTO for lenalidomide (81.5 days) compared to pomalidomide (134 days). High-risk subgroups included males, elderly patients (65-85 years), and individuals with obesity (> 100 kg). The PI3K-Akt pathway emerged as a central mechanism for endothelial dysfunction and thrombogenesis. Pomalidomide showed additional enrichment in fluid shear stress and TNF signaling pathways. Literature analysis confirmed alignment with core topics such as thrombotic events, platelet function, and prophylactic anticoagulation. Our findings highlight an urgent need to shift from empirical anticoagulation to precision-based thromboprophylaxis in patients treated with CRBN-targeting IMiDs. Early-onset PE risk is mechanistically linked to vascular endothelial injury and inflammatory signaling, supporting the use of dynamic risk stratification tools (e.g., IMPEDE-VTE score) and early DOAC intervention. Public health policy should integrate molecular insights with real-world surveillance to optimize clinical safety frameworks for oncology patients.
Outcomes of Venous-Arterial Extracorporeal Membrane Oxygenation Therapy in Acute Pulmonary Embolism: A Single-Center Experience.
Chiang CJ, Alhuneafat L, Salama PS … +4 more , Elliott AM, Yannopoulos D, Bartos JA, Gutierrez Bernal A
J Thromb Thrombolysis · 2026 May · PMID 42159966 · Publisher ↗
Outcomes of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy in acute pulmonary embolism. High-risk pulmonary embolism (PE) has a high mortality risk. VA-ECMO provides essential cardiopulmonary suppo...
Outcomes of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy in acute pulmonary embolism. High-risk pulmonary embolism (PE) has a high mortality risk. VA-ECMO provides essential cardiopulmonary support, although data outcomes remain limited. We sought to describe the characteristics and clinical outcomes of patients supported with VA-ECMO for the management of high-risk PE. We retrospectively analyzed outcomes of adult patients treated with VA-ECMO for high-risk PE at the University of Minnesota between January 2015 and May 2024. High-risk PE was defined by the European Society of Cardiology criteria. Clinical, demographic, procedural, and outcome data were analyzed. Mortality predictors were assessed using logistic regression. Of 1350 patients supported by VA-ECMO, 58 (4.3%) presented with high-risk PE (69% cardiac arrest, 31% shock). Mortality was significantly higher among patients cannulated for cardiac arrest than for shock (72.5% vs. 33.3%, P = 0.005). An independent predictor of mortality was out-of-hospital cardiac arrest (OR 6.67, 95% CI 1.15-38.7, P = 0.035). The duration of CPR was shorter among survivors (25.9 vs. 44.2 min, P = 0.02). Neither catheter-directed therapy nor systemic thrombolysis was associated with survival. Major bleeding occurred in 67% of patients and was not significantly associated with mortality. Neurologic injury was the leading cause of death in cardiac arrest patients; multiorgan failure predominated in the shock group. Despite the use of VA-ECMO, mortality in high-risk PE remains elevated, but differed by indication for cannulation. Survival was higher in patients presenting with shock, in-hospital cardiac arrest, shorter CPR duration, and sustained return of spontaneous circulation. Further research is needed to define the role of VA-ECMO and adjunctive therapies across varied clinical presentations.
Association between JAK2 mutations and thoracic aortic aneurysms in myeloproliferative neoplasms.
Dulli MW, Ahmed A, Altermanini M … +5 more , Kaddoura R, Al-Mashdali AF, Abdulgayoom M, Imam Y, Mohamed SF
J Thromb Thrombolysis · 2026 May · PMID 42154105 · Publisher ↗
The Janus kinase 2 (JAK2) V617F mutation is recognized as a defining molecular lesion in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). This mutation was recognized in the context of clonal hematop...
The Janus kinase 2 (JAK2) V617F mutation is recognized as a defining molecular lesion in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). This mutation was recognized in the context of clonal hematopoiesis of indeterminate potential, which has recently been linked with cardiovascular disease. Recent evidence has demonstrated a significant correlation between JAK2 mutations and thoracic aortic aneurysm (TAA) a condition frequently lacking identifiable risk factors. A scoping review, involving MEDLINE, Embase, Web of Science, Google Scholar, and prominent hematology and cardiology conference abstracts (from inception to August 2025) was performed. All studies that indicate a correlation between JAK2 mutations and aortic aneurysms were included. Seven studies with a total of 446,839 participants were found. Among these, 745 (0.17%) tested positive for JAK2. Data consistently indicated an elevated risk of thoracic aortic aneurysm (TAA), but not abdominal aortic aneurysm, in individuals with JAK2 mutations. Proposed mechanisms include inflammatory cytokine signaling, macrophage activation, and degradation of the extracellular matrix. Emerging clinical data indicate a consistent association between JAK2 V617F-mutated clonal hematopoiesis or myeloproliferative neoplasms and thoracic aortic aneurysm, with less consistent findings for abdominal aneurysm. Although experimental studies suggest that JAK2-driven inflammatory signaling and extracellular matrix remodeling may contribute to vascular wall injury, these mechanisms remain largely inferential and do not establish causality. Well-designed prospective investigations incorporating standardized imaging, uniform aneurysm definitions, and stratification by clonal burden and disease context will be necessary to better define risk and determine whether JAK2-associated clonal hematopoiesis has implications for vascular surveillance or prevention strategies.
Multi-step computational identification of small molecules targeting the TLT-1 stalk peptide: structural insights into platelet function and thrombosis.
Alenazy FO
J Thromb Thrombolysis · 2026 May · PMID 42149313 · Publisher ↗
The need for safer and more targeted antithrombotic medications is highlighted by the fact that platelet activation and thrombosis are significant causes of cardiovascular morbidity and mortality. Potential small molecul...
The need for safer and more targeted antithrombotic medications is highlighted by the fact that platelet activation and thrombosis are significant causes of cardiovascular morbidity and mortality. Potential small molecules targeting Triggering Receptor Expressed on Myeloid Cells-Like Transcript-1 (TLT-1), expressed by the TREML1 gene that regulates platelet aggregation and thrombus stabilization, were identified in this study using a thorough in silico approach. Protein-protein interaction analysis, Gene Ontology, KEGG pathway enrichment, and GTEx-based tissue expression were used in network pharmacology of TREML1 to demonstrate its connection to thrombotic processes and platelet activation. Pharmacophore models were created utilizing TLT-1 stalk peptide residues based on the 8CHE crystal structure, and Pharmit was used to screen virtual libraries of synthetic and natural chemicals. AutoDock Vina was used for molecular docking, and compounds with docking scores ≤ - 7.0 kcal/mol were shortlisted, producing 81 synthetic and 27 natural hits. Two natural (ZINC000225509830 and ZINC000015671940) and three synthetic (ZINC000063467474, ZINC000215029558, and ZINC000257255111) candidates were selected after further ADME and toxicity profiling. Interaction profiling revealed that the synthetic compound ZINC000063467474 showed strong hydrogen bonding and π-π stacking interactions with low projected toxicity, whereas the natural compound ZINC000225509830 also showed extensive engagement with TLT-1 stalk-peptide residues. According to molecular dynamics simulations, ZINC000063467474 maintained steady and persistent binding within the TLT-1 pocket for 100 ns, whereas the natural compound exhibited positional drift and decreased stability. These results indicate that ZINC000063467474 may serve as a promising scaffold for targeting the TLT-1 stalk peptide and represents a potential lead for modulating platelet function and thrombosis; however, this requires further experimental validation.
Copeptin in acute ischemic stroke: a surrogate marker of AVP-system activation with temporal dynamics and clinical implications.
Lei M, Huang Y, Xu H … +3 more , Deng Y, Tang L, Zhao C
J Thromb Thrombolysis · 2026 May · PMID 42149312 · Publisher ↗
Copeptin, an inert peptide derived from provasopressin and co-released with arginine vasopressin (AVP), has emerged as a stable circulating indicator of AVP system activation and has attracted growing interest in acute i...
Copeptin, an inert peptide derived from provasopressin and co-released with arginine vasopressin (AVP), has emerged as a stable circulating indicator of AVP system activation and has attracted growing interest in acute ischemic stroke (AIS). Over the past decade, both experimental and clinical investigations have explored its potential clinical relevance. A central challenge, however, is to distinguish the biological role of AVP signaling from the interpretive significance of copeptin as a biomarker. Current evidence indicates that AVP signaling may contribute to key pathological processes, including cerebral edema formation and post-ischemic inflammatory responses. In contrast, copeptin appears to reflect activation of the neuroendocrine stress axis rather than acting as a direct effector within these pathways. Clinically, copeptin levels rise rapidly during the early phase of AIS and are consistently associated with stroke severity and adverse outcomes, supporting its potential utility in early risk stratification and prognostic assessment. The use of copeptin in combination with neuroimaging parameters and other biomarkers has been explored, with some studies suggesting improved performance in early clinical evaluation. However, whether copeptin confers meaningful incremental value beyond established tools remains uncertain. Interpretation of the available evidence is further limited by heterogeneity in study design, variability in sampling strategies, the lack of standardized cutoff values, and the scarcity of large-scale prospective validation. Taken together, copeptin may serve as a useful component within multimarker frameworks for AIS. Its clinical interpretation, however, should remain anchored to its role as a surrogate indicator of AVP pathway activation, rather than being extended to a direct mediator of ischemic injury.
Protein-protein interaction disruption as a next-generation antithrombotic strategy.
Kamel EM, Khadrawy SM, Ali MAM … +5 more , Ahmed NA, Yassin NYS, Alkhedhairi S, Alkhayl FFA, Lamsabhi AM
J Thromb Thrombolysis · 2026 May · PMID 42149311 · Publisher ↗
Thrombosis is built, not merely catalyzed. Across arterial and venous disease, thrombus formation depends on a succession of protein-protein interactions (PPIs) that coordinate platelet capture and activation, thromboinf...
Thrombosis is built, not merely catalyzed. Across arterial and venous disease, thrombus formation depends on a succession of protein-protein interactions (PPIs) that coordinate platelet capture and activation, thromboinflammatory amplification, and assembly of membrane-bound coagulation complexes. Although active-site inhibitors and receptor antagonists have transformed antithrombotic therapy, clinical benefit is often constrained by bleeding because many targets are indispensable for everyday hemostasis when inhibited systemically. This review advances a "thrombus assembly" framework that reframes drug discovery around disrupting interfaces that organize pathologic clot growth in a context-dependent manner shaped by shear, surfaces, local cofactors, and transient complex formation. We highlight translational proof that interface blockade works in humans, focusing on VWF A1-GPIbα inhibition and GPVI-directed strategies as exemplars of lesion- and shear-dependent antiplatelet therapy. We then survey platelet adhesion and activation PPIs (VWF-GPIb, collagen-GPVI, and αIIbβ3-ligand interactions), thromboinflammatory interfaces (including P-selectin-PSGL-1 and CLEC-2-podoplanin), and opportunities to target coagulation complex assembly and thrombin exosites without directly inhibiting catalytic active sites. A modality-focused section links interface class to therapeutic format-antibodies/nanobodies, aptamers with antidotes, peptides and macrocycles, and small-molecule PPI inhibitors-and summarizes trade-offs in reversibility, half-life, manufacturability, and immunogenicity. Finally, we discuss assays that preserve interface biology (whole-blood flow systems, microfluidics, thrombin generation, and clot mechanics) and propose clinical positioning and trial endpoints for context-gated mechanisms. By targeting the contacts that assemble and stabilize thrombi, PPI disruption offers a pragmatic route toward more selective, potentially bleeding-sparing antithrombotic therapy and a roadmap for next-generation pipeline development.
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