Thrombosis Research[JOURNAL]
Sun
200 papers
Apoptotic versus procoagulant platelets: similar "necrotic" phenotype and procoagulant activity in vitro, but distinct adhesive protein composition.
Podoplelova NA, Obydennyi SI, Ignatova AA … +12 more , Soloveva PA, Chabin IA, Dasgupta AKG, Filkova AA, Starostin NN, Sokolov AV, Kireev II, Balashova EN, Trakhtman PE, Novichkova GA, Sveshnikova AN, Panteleev MA
Thromb Res · 2026 Jun · PMID 42391998 · Publisher ↗
Platelets can undergo at least two distinct types of regulated cell death, apoptosis and mPTP-driven necrosis. Apoptosis is believed to be responsible for platelet clearance, while strong platelet activation by physiolog...
Platelets can undergo at least two distinct types of regulated cell death, apoptosis and mPTP-driven necrosis. Apoptosis is believed to be responsible for platelet clearance, while strong platelet activation by physiological agonists leads to necrosis, producing procoagulant platelet remnants that are essential for blood coagulation during thrombosis and hemostasis. To thoroughly compare morphological and functional features of apoptotic and necrotic-like procoagulant platelets in vitro, their procoagulant activity, ability to bind coagulation proteins, and adhesive protein composition were evaluated. Confocal and electron microscopy were used to analyze morphology. Both apoptotic and necrotic-like procoagulant platelets had balloon-shaped morphology with phosphatidylserine-enriched "caps", as well as similar abilities to bind blood coagulation factors and participate in procoagulant reactions. However, apoptotic platelets did not release their alpha-granules and, consequently, did not have the "coat" of alpha-granular proteins such as P-selectin, fibrin(ogen), and von Willebrand factor on their surface, which was characteristic for the necrotic-like procoagulant ones. They were completely unable to bind external fibrinogen. They were completely unable to bind external fibrinogen. During storage of platelet concentrates, PS-positive platelets of both apoptotic (PS/CD62P) and necrotic-like procoagulant (PS/CD62P) phenotypes were observed to accumulate.
Heatstroke-induced coagulopathy: A scoping review of therapeutic strategies and outcome reporting.
Yasuda T, Satoh K, Imai K … +4 more , Maeno K, Okuyama M, Koami H, Nakae H
Thromb Res · 2026 Jun · PMID 42379077 · Publisher ↗
Heatstroke-induced coagulopathy (HSIC) is a life-threatening complication of heatstroke that often progresses to disseminated intravascular coagulation. Despite its prognostic significance, standardized treatment strateg...
Heatstroke-induced coagulopathy (HSIC) is a life-threatening complication of heatstroke that often progresses to disseminated intravascular coagulation. Despite its prognostic significance, standardized treatment strategies have not yet been established. This scoping review aimed to systematically map existing treatment approaches and outcome measures for HSIC in both clinical and experimental research. We conducted a scoping review in accordance with PRISMA-ScR and the Joanna Briggs Institute methodology. Literature searches were conducted in MEDLINE, Web of Science, and Scopus on June 2, 2025. To enhance relevance to contemporary clinical practice, inclusion was limited to studies published from January 2010 onward. Eligible studies included clinical and basic research evaluating treatment interventions for HSIC. A total of 61 studies were included, comprising clinical studies, case reports/series, reviews, editorials, and basic research. Only two clinical studies evaluated treatments using control groups. Anticoagulants such as antithrombin and recombinant thrombomodulin were evaluated, but clinical evidence remained limited. Case reports and case series frequently described transfusion therapies, particularly platelet and fresh frozen plasma administration. However, standardized treatment protocols were lacking, and outcome assessments were mostly descriptive. Basic research explored multiple therapeutic candidates targeting inflammation and coagulation pathways, but clinical application remained limited. These findings suggest that progress in HSIC therapeutics is hampered not only by a lack of controlled trials, but also by the absence of standardized diagnostic criteria, assessment timepoints, and outcome measures across studies. A consensus framework for standardizing diagnostic and outcome reporting in HSIC, alongside multicenter registries and translational research, is an urgent priority for the field.
Mapping thrombus habitat: Non-contrast MRI radiomics and pixel-tile histomics approach to track venous thrombosis evolution in mice.
Yao S, Wu X, Liu Y … +5 more , Zhang X, Liu Q, Xing Y, Di X, Chen Y
Thromb Res · 2026 Jun · PMID 42372540 · Publisher ↗
BACKGROUND: Determining the age and composition of deep vein thrombosis (DVT) is essential for optimizing thrombus removal strategies, yet clinical decision-making remains restrained by the subjectivity of symptom-based...
BACKGROUND: Determining the age and composition of deep vein thrombosis (DVT) is essential for optimizing thrombus removal strategies, yet clinical decision-making remains restrained by the subjectivity of symptom-based assessment. We applied non-contrast T1/T2 weighted MRI radiomics with habitat clustering to quantify thrombus evolution, validating MRI habitats against histopathology with translational clinical potential. METHODS: Venous thrombosis was induced in BALB/c mice using a refined inferior vena cava ligation model to ensure consistent thrombus development. Longitudinal and cross-sectional cohorts were imaged at 7 T MRI with T1- and T2-weighted sequences on post-ligation days 2, 7, and 14. Thrombus regions were delineated using a hybrid approach and voxel-level radiomic features were extracted. Unsupervised K-Means clustering defined MRI-based habitats. Imaging signatures were correlated with an artificial neural network pixel classifier and tile-based histomics clustering to quantify red blood cells (RBC), fibrin, and collagen. RESULTS: Radiomic analysis showed a decline in Energy and TotalEnergy and a similar trend in GrayLevelNonUniformity, reflecting a transition from acute to more uniform chronic thrombi. A two habitats strategy could differentiate acute RBC-rich regions from fibrotic components. Histology confirmed RBC-rich areas fell from 88.22% to 6.52% over 14 days, while collagen-rich areas rose from 0.16% to 79.67%. MRI habitat proportions correlated strongly with histological tile clusters (Spearman r = 0.74, p = 0.0005). CONCLUSION: Multiparametric MRI radiomics combined with habitat analysis captures thrombus composition and temporal evolution, with unsupervised histomics providing biological validation. These findings support the translational potential of MRI habitat analysis as a non-invasive biomarker of thrombus heterogeneity.
A study protocol for a randomised controlled trial evaluating the safety and efficiency of the YEARS algorithm versus computed tomography pulmonary angiography only for suspected acute pulmonary embolism in patients with cancer: the Hydra Study.
Martens ESL, Akerboom B, Baumgartner C … +34 more , Brouwer RE, Cavallaro C, Coppens M, Costantino G, Couturaud F, D'Errico A, van Dooren YPA, Gianni F, van der Griend R, Grootenboers MJJH, Hugli O, van der Hulle T, Jaderi Z, Jiménez D, Kamphuisen PW, Lanting VR, Leentjens J, Maas ML, Mahé I, van Meer OA, van Mens TE, Out M, Pola R, Pulver D, Raskin J, Righini M, Sprenger RA, Stals MAM, Talerico R, Tritschler T, Ten Wolde M, Klok FA, Huisman MV, HYDRA study group. Electronic address: research_interne@lumc.nl
Thromb Res · 2026 Jun · PMID 42365759 · Publisher ↗
BACKGROUND: Pulmonary embolism (PE) is frequently suspected in patients with cancer due to non-specific symptoms suggestive of PE and their inherent risk of venous thromboembolism (VTE). Commonly used clinical decision r...
BACKGROUND: Pulmonary embolism (PE) is frequently suspected in patients with cancer due to non-specific symptoms suggestive of PE and their inherent risk of venous thromboembolism (VTE). Commonly used clinical decision rules (CDRs) and D-dimer testing may be less reliable in this specific population. Due to the lack of guideline recommendations on the optimal diagnostic approach and the perceived futility of D-dimer in patients with cancer, clinicians often use computed tomography pulmonary angiography (CTPA) as a sole diagnostic test. This practice exposes patients to potentially unnecessary radiation and harm, and contributes to a significant burden on healthcare systems through inefficient resource allocation. The YEARS algorithm is an easy-to-use CDR that has been shown to safely exclude PE without the need for CTPA in a diverse population of patients with suspected PE. OBJECTIVE: To compare the safety and efficiency of the YEARS algorithm to the safety and efficiency of CTPA only in the diagnostic management of acute PE in cancer patients. DESIGN AND INTERVENTIONS: The Hydra study (ClinicalTrials.govNCT04657120) is an investigator-initiated, multicentre, multinational open-label, randomised, non-inferiority trial with blinded adjudication of outcome events, comparing the YEARS algorithm with CTPA only in the diagnostic work-up of cancer patients with clinically suspected acute PE. Participants are randomised in a 1:1 ratio to each diagnostic strategy via a web-based system. The trial anticipates to include 1566 patients. PARTICIPANTS: Consecutive patients with active cancer who are hospitalised or present to the emergency department, outpatient clinic, or thrombosis clinic with clinically suspected PE and who are not receiving therapeutic anticoagulation or have an indication for anticoagulation therapy other than PE. STUDY OUTCOMES: The primary safety outcome is the proportion of symptomatic and objectively proven fatal or non-fatal VTE (i.e., PE or deep vein thrombosis in the upper or lower extremities) or death with undetermined cause where acute PE could not be ruled out as contributing factor during three months follow-up in patients in whom PE was ruled out at initial testing. The primary efficiency outcome is the proportion of negative CTPA scans for PE, relative to the total number of CTPA scans performed at initial testing. IMPLICATION: This trial will provide pivotal data on the optimal diagnostic approach for suspected acute PE in patients with cancer.
Associating the phenotypic expression of platelets with disease type through image-based single-cell profiling.
Wang H, Nishikawa M, Zhou Y … +9 more , Yang R, Chen J, Zhang H, Ibayashi Y, Kanno H, Kurano M, Morishita E, Yatomi Y, Goda K
Thromb Res · 2026 Jun · PMID 42365758 · Publisher ↗
BACKGROUND: Platelets are central to hemostasis and thrombosis and contribute to diverse diseases, including cardiovascular disorders, infections, and cancer. Although platelet activation and dysfunction in disease have...
BACKGROUND: Platelets are central to hemostasis and thrombosis and contribute to diverse diseases, including cardiovascular disorders, infections, and cancer. Although platelet activation and dysfunction in disease have been studied extensively, disease-associated platelet phenotypes remain poorly defined, largely because phenotypic changes are subtle, transient, and difficult to capture at single-cell resolution. METHODS: We acquired bright-field images of numerous circulating platelets in whole-blood samples anticoagulated with 3.2% sodium citrate that were collected from patients (n = 65) and healthy volunteers (n = 10) at the University of Tokyo Hospital, using optofluidic imaging with an optical frequency-division-multiplexed (FDM) microscope integrated with a microfluidic chip. Convolutional neural network (CNN) models were trained to classify platelet phenotypes across disease categories. Feature-importance analysis was performed to identify image-derived parameters driving the deep-learning-based characterization. RESULTS: We developed three CNN models to classify platelet images by disease category, achieving accuracies of up to 81.3%, indicating measurable associations between platelet phenotypic expression and disease type. Longitudinal analysis of platelet images further showed that the CNN models could predict thrombotic progression up to 7 days before clinical thrombus detection. Feature-importance analysis highlighted texture-related descriptors as the dominant contributors, accounting for 54.5% of overall importance. CONCLUSIONS: Image-based analysis of circulating platelets can capture disease-associated phenotypic signatures and may complement existing clinical workflows for prediagnosis and early assessment of thrombotic risk.
The mechanisms of contractile dysfunction following chronic limited platelet activation in (pro)thrombotic conditions.
Khabirova AI, Khismatullin RR, Saliakhutdinova SM … +2 more , Litvinov RI, Weisel JW
Thromb Res · 2026 Jun · PMID 42364348 · Publisher ↗
BACKGROUND: Patients with (pro)thrombotic conditions often exhibit a combination of platelet activation and dysfunction, including impaired contractility, which may contribute to thrombosis progression. AIMS: To study th...
BACKGROUND: Patients with (pro)thrombotic conditions often exhibit a combination of platelet activation and dysfunction, including impaired contractility, which may contribute to thrombosis progression. AIMS: To study the mechanisms of secondary platelet dysfunction developed during prolonged limited activation in vitro. METHODS: Platelet-rich plasma from healthy subjects was incubated with 10 μM thrombin receptor-activating peptide (PAR1-receptor agonist) for 6 h at 37 °C to simulate continuous incomplete platelet activation. The dynamic functional and morphological state of platelets was assessed at specific time points by the rate and degree of thrombin-induced clot contraction, the mitochondrial membrane potential, intracellular ATP content, expression of phosphatidylserine, P-selectin and active integrin αIIbβ3 (before and after hyper-stimulation), platelet aggregation, as well as by scanning electron microscopy. RESULTS: In long-term activated platelets, a significant decrease in contractility was observed, while in control untreated plasma samples the contractility remained relatively stable throughout the 6-h observation period. Continuing platelet activation was accompanied by a decrease in the mitochondrial membrane potential and intracellular ATP level. An increase in expression of phosphatidylserine and P-selectin was steady, while the expression of active integrin αIIbβ3 was initially elevated, but dropped eventually, which disrupts platelet aggregation and mechanotransmission from contracting platelets to fibrin. Morphologically, the activated platelets initially formed aggregates followed by disaggregation along with progressive platelet inactivation and fragmentation. CONCLUSIONS: The reduced platelet contractility in (pro)thrombotic conditions results from continuing limited activation of circulating platelets, leading to multiple functional and structural impairments, altogether underlying 'activation-induced platelet dysfunction', a particular and common type of acquired thrombocytopathy.
Molecular basis of the E69Q and R383W heterozygous F2 variants identified in the proband associated with severe hemostatic defects.
Lin L, Li Y, Chen C … +6 more , Yuan J, Wu X, Wu W, Wang X, Ding Q, Dai J
Thromb Res · 2026 Jun · PMID 42361492 · Publisher ↗
BACKGROUND: Functional studies of F2 variants causing congenital prothrombin deficiency are few. OBJECTIVES: To investigate the molecular basis of dysprothrombinemia in a proband with severe bleeding manifestations and r...
BACKGROUND: Functional studies of F2 variants causing congenital prothrombin deficiency are few. OBJECTIVES: To investigate the molecular basis of dysprothrombinemia in a proband with severe bleeding manifestations and reduced prothrombin activity (5.7%) and antigen levels (28.5%). METHODS: Genetic analysis was performed using the targeted gene panel sequencing. Variant prothrombins were expressed and characterized in kinetic assays. The binding capacity of the variant prothrombin to phospholipid membranes was analyzed using surface plasmon resonance. RESULTS: Two heterozygous F2 variants (E69Q and R383W) were identified in the proband. The secretion of R383W prothrombin was severely impaired (5% of WT). The activation of FVIII by the R383W thrombin was severely impaired, resulting from reduced catalytic rate toward FVIII (k ∼ 10-fold). Interaction with soluble thrombomodulin (sTM) was significantly weakened (K ∼ 8-fold), resulting in impaired protein C activation in the presence of sTM. The E69Q prothrombin exhibited a markedly weaker phospholipid binding capacity (K ∼ 100-fold), and the activation of the variant by the prothrombinase complex was severely impaired (∼600-fold). CONCLUSIONS: The impaired catalytic rate toward FVIII of the R383W variant indicated that the R383 residue, located in exosite I, played a role in regulation of the active-pocket function of thrombin. Thus the variant disrupted the timely amplification of thrombin generation. The E69Q prothrombin exhibited a profound defect of zymogen activation, the E69 residue was critical for calcium-dependent phospholipid binding and procoagulant activity. These findings highlight that comprehensive functional evaluations are essential for elucidating the mechanisms of F2 variants underlying bleeding phenotypes.
Direct oral anticoagulants versus vitamin K antagonists for the treatment of cerebral venous thrombosis: A systematic review and meta-analysis of randomized clinical trials.
Delrue M, Crichi B, Crassard I … +2 more , Le Jeune S, Frere C
Thromb Res · 2026 Jun · PMID 42361491 · Publisher ↗
BACKGROUND: Current guidelines consider direct oral anticoagulants (DOACs) a reasonable treatment option for cerebral venous thrombosis (CVT), but randomized evidence comparing DOACs vs. vitamin K antagonists (VKAs) rema...
BACKGROUND: Current guidelines consider direct oral anticoagulants (DOACs) a reasonable treatment option for cerebral venous thrombosis (CVT), but randomized evidence comparing DOACs vs. vitamin K antagonists (VKAs) remain limited. OBJECTIVE: To compare the efficacy and safety of DOACs vs. VKAs for CVT treatment. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing DOACs with VKAs in adults with CVT. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through January 2026. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Peto method. Primary outcomes included recurrent venous thromboembolism (VTE) and intracranial hemorrhage (ICH). Secondary outcomes comprised complete venous recanalization, major bleeding, clinically relevant non-major bleeding (CRNMB), any bleeding, and all-cause mortality. RESULTS: Of 267 records screened (23 full texts assessed), 6 RCTs (428 patients: DOAC n = 213, VKA n = 215) were included. All studies had some risk of bias. Anticoagulant treatment duration ranged from 3 to 12 months, and follow-up ranged from 6 to 12 months. For recurrent VTE, the OR was 3.14 (95% CI 0.95-10.37). No significant differences between groups emerged for ICH (OR 1.37, 95% CI 0.31-6.16), recanalization, major bleeding, CRNMB, or mortality. Any bleeding risk was significantly lower with DOACs (OR 0.54, 95% CI 0.29-1.00). GRADE certainty was low across all outcomes due to imprecision. CONCLUSION: These findings suggest comparable efficacy and safety between DOACs and VKAs for CVT but require considerable caution given the small sample size, rare events, wide CIs, and low certainty evidence.
Prospective comparison of viscoelastic coagulation monitor (VCM) and rotational thromboelastometry (ROTEM) in the assessment of cirrhosis coagulopathy.
Pinto E, Zanetto A, Campello E … +7 more , Bulato C, Gerli F, Ferdinande K, Russo FP, Burra P, Senzolo M, Simioni P
Thromb Res · 2026 Jun · PMID 42349305 · Publisher ↗
BACKGROUND: Rotational thromboelastometry (ROTEM) provides comprehensive hemostasis assessment in cirrhosis but relies on exogenous activators, potentially limiting its reflection of in vivo conditions. The Viscoelastic...
BACKGROUND: Rotational thromboelastometry (ROTEM) provides comprehensive hemostasis assessment in cirrhosis but relies on exogenous activators, potentially limiting its reflection of in vivo conditions. The Viscoelastic Coagulation Monitor (VCM) is a new, activator-free device to assess whole-blood coagulation dynamics. OBJECTIVES: To investigate the concordance between VCM and ROTEM and to explore their association with clinical outcomes in cirrhosis. METHODS: We prospectively included 110 patients with cirrhosis admitted to our service. VCM and ROTEM were performed at hospitalization. All patients were followed up for bleeding, thrombosis, hepatic decompensation and liver-related mortality. RESULTS: Patients were mostly male (68.2%) with a median age of 61 years (53-68). Alcohol-related liver disease was the most common etiology (44.5%). 16.4% of patients were Child-Pugh A, 39.1% B, and 32.7% C. Inter-test analysis showed that parameters of VCM and ROTEM had moderate to strong correlation (ρ = 0.37-0.84, p < 0.0001). We observed progressive, significant alterations of VCM in parallel with disease severity (Child-Pugh C > B > A). In contrast, ROTEM was comparable between Child-Pugh A and B patients, being altered only in Child-Pugh C cirrhosis. The median follow-up was 11 months (7-13). No patient experienced bleeding or thrombosis. Incidence of hepatic decompensation and liver-related death was 27.2% and 14.5%, respectively. No VCM parameter was associated with decompensation/death. CONCLUSIONS: In a prospective cohort of hospitalized cirrhosis patients, VCM showed more gradual hemostatic changes across disease severity stages than ROTEM. However, neither test predicted decompensation or liver-related death, indicating that viscoelastic assessment alone is insufficient for prognosis. Further studies are needed to define VCM's role in cirrhosis management.
Comparative effectiveness and safety of rituximab and caplacizumab for immuno-mediated Thrombotic Thrombocytopenic Purpura: an overview of systematic reviews.
Carvalho-Ribeiro M, Peña C, Nóbrega TDR … +2 more , Visacri MB, Orsi FA
Thromb Res · 2026 Jun · PMID 42349304 · Publisher ↗
BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disorder caused by anti-ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) antibodies...
BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disorder caused by anti-ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) antibodies. Although therapeutic plasma exchange (TPE) and corticotherapy have long been the standard of care (SOC), rituximab and caplacizumab are increasingly incorporated into clinical practice. Given that these drugs significantly increase the costs of iTTP treatment, synthesizing the available evidence is important for coverage decisions in resource-limited settings. OBJECTIVES: To summarize and critically appraise systematic reviews with meta-analyses (SRMAs) evaluating effectiveness and safety of rituximab and caplacizumab for iTTP treatment. METHODS: PubMed, EMBASE, the Cochrane Library, and LILACS were searched up to August 2025. Two reviewers screened citations, with disagreements resolved by a third reviewer. Data extraction was performed by one reviewer and verified by another. Findings were synthesized narratively. RESULTS: Seven SRMAs were included: two evaluated rituximab and five caplacizumab. SRMAs of rituximab included non-randomized studies and reported reductions in mortality and relapse when added to SOC, although exacerbation and safety were not assessed. SRMAs of caplacizumab included two randomized and nine non-randomized studies. Mortality reduction with caplacizumab was not demonstrated in randomized trials, although real-world data suggested a survival benefit. Randomized trials showed reduced risk of exacerbation and increased risk of bleeding, but no consistent effect on relapse. All SRMAs were rated as critically low methodological quality. CONCLUSION: Although SRMAs suggest rituximab and caplacizumab may improve clinical response and survival, with more consistent evidence favoring rituximab, their critically low methodological quality highlights limitations in the current evidence base.
Altered IGF-1R, p70S6K, and GSK-3β expression in PBMCs of immune thrombocytopenia patients and clinical associations.
Zhou X, Shi Y, Liu Y … +3 more , Jiang Y, Liu S, Shan N
Thromb Res · 2026 Jun · PMID 42349303 · Publisher ↗
OBJECTIVE: To investigate the expression profiles of insulin-like growth factor-1 receptor (IGF-1R), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in peripheral blood mononuclear cells (PBMCs) of adults...
OBJECTIVE: To investigate the expression profiles of insulin-like growth factor-1 receptor (IGF-1R), p70S6 kinase (p70S6K), and glycogen synthase kinase-3β (GSK-3β) in peripheral blood mononuclear cells (PBMCs) of adults with newly diagnosed primary immune thrombocytopenia (ITP), and to evaluate their associations with clinical hematologic parameters. METHODS: A case-control study was conducted enrolling 30 adults with newly diagnosed primary ITP and 28 healthy volunteers. PBMCs were isolated from peripheral venous blood. The expression levels of Akt/mTOR pathway-related proteins were quantified using a high-throughput multiplex Luminex xMAP platform. Statistical analyses were performed to compare protein levels between the ITP and control groups and to assess the correlations between these signaling molecules and peripheral blood indices, specifically platelet counts. In addition, a small cohort of patients with chemotherapy-induced thrombocytopenia (CTIT) was included in the RT-qPCR validation analysis to further explore disease specificity. RESULTS: Compared with healthy controls, patients with ITP showed significantly elevated protein levels of IGF-1R and GSK-3β in PBMCs after FDR correction, whereas p70S6K showed only a nominal increase that did not remain significant after multiple-testing correction. RT-qPCR validation further showed significant upregulation of p70S6K and GSK-3β mRNA levels, with a concordant but non-significant increasing trend in IGF-1R mRNA. No significant differences were observed in other pathway components (e.g., Akt, mTOR, PTEN) or across different age and gender subgroups within the patient cohort. Notably, the expression levels of IGF-1R and p70S6K showed a significant negative correlation with peripheral platelet counts (P < 0.05), whereas no significant associations were found with red blood cell counts, hemoglobin, or white blood cell counts. In the validation analysis, comparison with the chemotherapy-induced thrombocytopenia cohort suggested that these alterations were more pronounced in ITP rather than representing a nonspecific consequence of thrombocytopenia. CONCLUSION: The altered expression of IGF-1R and GSK-3β, together with the potential involvement of p70S6K supported by transcriptional validation, may be associated with thrombocytopenia severity in newly diagnosed ITP, suggesting dysregulation of immunometabolic signaling in PBMCs.
Prevalence and clinical outcomes associated with proximal deep vein thrombosis at hospital admission detected by bedside ultrasound in patients hospitalized in a medical oncology ward: An exploratory prospective study.
Teigell Muñoz FJ, García-Ferrón M, Mateos-González M … +5 more , Bernal Hertfelder E, Sánchez de Torre A, Paredes Ruiz D, Sevo Spahiu S, Bueno Muiño C
Thromb Res · 2026 Jun · PMID 42341495 · Publisher ↗
BACKGROUND: Venous thromboembolism (VTE) is a frequent and serious complication in patients with cancer. Although lifetime VTE risk is well established, data on the prevalence of proximal deep vein thrombosis (pDVT) at h...
BACKGROUND: Venous thromboembolism (VTE) is a frequent and serious complication in patients with cancer. Although lifetime VTE risk is well established, data on the prevalence of proximal deep vein thrombosis (pDVT) at hospital admission are lacking, particularly in medical oncology wards. OBJECTIVES: To explore the prevalence of pDVT at hospital admission in patients with cancer using systematic bedside ultrasound screening, and to explore associated clinical factors and outcomes. METHODS: We conducted a prospective, single-center prevalence study including adult patients with solid tumors admitted to a medical oncology ward. Bilateral lower-extremity point-of-care ultrasound using a simplified compression technique was performed within 72 h of admission. Clinical, laboratory, and oncologic variables were recorded. Associations with pDVT were analyzed using univariable and multivariable logistic regression. RESULTS: A total of 203 patients were included. pDVT was detected in 16 patients (7.9%). The prevalence of pDVT increased with worsening functional status. In multivariable analysis, an ECOG performance status ≥2 and a Khorana score ≥2 were independently associated with pDVT at admission. Patients with pDVT had higher in-hospital mortality (31.3% vs 8.0%) and significantly shorter overall survival (median 36 vs 176 days; p < 0.001). No in-hospital deaths were directly attributable to VTE. CONCLUSIONS: Bedside ultrasound screening identified a clinically relevant prevalence of previously unrecognized pDVT at hospital admission among patients with cancer. pDVT was associated with poorer functional status, higher thrombotic risk, and worse prognosis. While the clinical benefit of routine screening remains uncertain, further studies are needed before screening strategies can be recommended in this setting.
Infection site modifies the prognostic impact of disseminated intravascular coagulation in sepsis.
Takayama W, Tomita N, Matsuo Y … +1 more , Morishita K
Thromb Res · 2026 Jun · PMID 42335529 · Publisher ↗
BACKGROUND: Disseminated intravascular coagulation (DIC) is a common, life-threatening sepsis complication. Although DIC severity is widely used for risk stratification, whether its prognostic impact varies by infection...
BACKGROUND: Disseminated intravascular coagulation (DIC) is a common, life-threatening sepsis complication. Although DIC severity is widely used for risk stratification, whether its prognostic impact varies by infection site remains unclear. METHODS: We conducted a retrospective cohort study of adults with sepsis admitted to a tertiary critical care center between 2015 and 2025. DIC was defined as a Japanese Association for Acute Medicine score of ≥4 on hospital days 1-3. Patients were grouped by infection site. The primary outcome was in-hospital mortality, and secondary outcomes were ventilator-free days (VFD) and intensive care unit-free days (IFD). Multivariable regression models adjusted for age and sex were used to evaluate the association between DIC and outcomes, including interaction analysis by infection site. RESULTS: Among 933 patients, 568 (60.9%) developed DIC. DIC was associated with higher mortality and fewer VFD and IFD, with the strongest mortality association in pulmonary (aOR 4.5, 95% confidence interval [CI] 2.2-8.3) and urinary tract infections (aOR 3.2, 95% CI 1.4-9.4) (P for interaction = 0.02). DIC most commonly became apparent on hospital day 2. CONCLUSIONS: The prognostic impact of DIC in sepsis varies by infection site. Sepsis-associated DIC may not represent a uniform entity across infection phenotypes. Further studies are needed to clarify site-specific risks and mechanisms to optimize treatment strategies.
The perils of extrapolation: Lessons from a prospective registry of catheter-related thrombosis in patients with cancer.
Pfeferman M, Piazza G
Thromb Res · 2026 Jun · PMID 42331685 · Publisher ↗
Abstract loading — click title to view on PubMed.
Postoperative thrombosis in patients with hemophilia and malignancy: Mechanisms and perioperative prevention and management - A scoping review.
Zhao L, Xie Y, Yan Z
Thromb Res · 2026 Jun · PMID 42322918 · Publisher ↗
Hemophilia is traditionally viewed as a hypocoagulable disorder, but the occurrence of postoperative venous thromboembolism (VTE) in these patients, particularly when malignancy is present, challenges this paradigm. Canc...
Hemophilia is traditionally viewed as a hypocoagulable disorder, but the occurrence of postoperative venous thromboembolism (VTE) in these patients, particularly when malignancy is present, challenges this paradigm. Cancer-related and surgery-induced prothrombotic factors, when combined with perioperative factor replacement, bypassing agents, or non-factor therapies, may transiently shift the patient from a hypocoagulable state to a prothrombotic one, creating a narrow therapeutic window where both bleeding and thrombosis are clinically significant. This review aims to synthesize the existing mechanistic and clinical evidence on postoperative thrombosis in hemophilia patients with malignancy and to identify where evidence is direct, indirect, or extrapolated. We outline a pragmatic, multidisciplinary team (MDT)-based framework for risk assessment, diagnosis, prophylaxis, and treatment, recognizing that the framework has not been validated in this rare population. A comprehensive scoping review was conducted using MEDLINE (PubMed), Embase, Web of Science, and the Cochrane Library, covering publications from 2000 to 2025. We also hand-searched major society guidelines and consensus documents. Direct evidence addressing postoperative VTE in patients with both hemophilia and malignancy was scarce; therefore, we separated direct hemophilia perioperative evidence from indirect cancer-surgery and mechanistic evidence used for contextual interpretation. Available hemophilia perioperative data are derived mainly from orthopedic cohorts and cannot define the incidence of postoperative VTE after cancer surgery in hemophilia. Reported thrombotic phenotypes include deep vein thrombosis (DVT), pulmonary embolism (PE), catheter-related thrombosis, and less commonly arterial events. Risk assessment should therefore integrate patient factors, cancer biology, surgical context, hemostatic treatment intensity, and FVIII/FIX peak and trough monitoring. Routine laboratory tests such as aPTT and D-dimer are frequently unreliable, supporting an imaging-first diagnostic strategy when VTE is clinically suspected. We present a four-tier VTE risk framework as a practical organizing tool rather than a validated prediction model. Pharmacologic thromboprophylaxis or therapeutic anticoagulation may be considered only after individualized bleeding-thrombosis assessment, stable surgical hemostasis, adequate factor coverage, and continuous MDT communication from preoperative planning to post-discharge care. Future research should focus on prospective registries, the development of standardized outcome definitions, and the validation of global coagulation assays to improve recommendations and management strategies in this evolving therapeutic landscape.
Outcome of catheter associated upper extremity deep vein thrombosis in cancer: A two year prospective study with enoxaparin.
Sartori M, Trentini A, Cavara S … +4 more , Favaretto E, Borgese L, Soldati M, Cosmi B
Thromb Res · 2026 Jun · PMID 42322917 · Publisher ↗
BACKGROUND: Current guidelines suggest three month anticoagulation for the treatment of catheter-related upper extremity deep vein thrombosis (CRT), but few data are available on outcome beyond three months in cancer pat...
BACKGROUND: Current guidelines suggest three month anticoagulation for the treatment of catheter-related upper extremity deep vein thrombosis (CRT), but few data are available on outcome beyond three months in cancer patients. METHODS: This was a prospective, single center study to ascertain the long term venous thromboembolism (VTE) recurrences for CRT in cancer patients. We enrolled 233 participants (age: 56.8 ± 16.6y, female: 58.4%) who received enoxaparin for 3 months. The follow-up was 24 months and the primary outcome was the composite measure of recurrent VTE. FINDINGS: 182 (78.1%) patients received therapeutic enoxaparin for 3 months whereas 51 (21.9%) patients continued therapeutic enoxaparin for 6 months. During the follow-up, the primary outcome occurred in 32 (13.7%) patients for a cumulative incidence rate of 9.2/100 patient years (95%CI: 6.6-12.7).There were: 28 (12.0%) CRT recurrences for a cumulative incident rate of 8.1/100 patient years, 3 (1.3%) pulmonary embolisms (0.9/100 patient years), and one (0.4%) cerebral venous sinus thrombosis (0.3/100 patient years). No patients in cancer remission had VTE recurrences. In multivariable modeling, insertion of a new vascular device (SHR 3.00, 95%CI: 1.14-7.88; p = 0.026) and the use prophylactic enoxaparin (SHR 0.05, 95%CI: 0.01-0.20; p < 0.001) were associated with the primary outcome, whereas the duration of therapeutic enoxaparin was not. INTERPRETATION: Recurrent VTE was not infrequent in subgroups of patients with CRT; these data may lead to improved risk stratification and to tailored management strategies.
A short history of anticoagulant therapy.
Chan NC, Imiela AM, Carlin S … +1 more , Hirsh J
Thromb Res · 2026 Jun · PMID 42322916 · Publisher ↗
Anticoagulant therapy has undergone a remarkable evolution over the past century, transforming the prevention and treatment of thromboembolic disease. The accidental discovery of vitamin K antagonists (VKAs) in the 1940s...
Anticoagulant therapy has undergone a remarkable evolution over the past century, transforming the prevention and treatment of thromboembolic disease. The accidental discovery of vitamin K antagonists (VKAs) in the 1940s, following investigations of fatal bleeding in cattle fed spoiled sweet clover, led to the identification of dicoumarol and the development of warfarin. Despite limitations in study design, studies from the 1960s onward established the foundations of modern anticoagulation. Subsequent advances refined the dosing and monitoring of heparin and VKAs, while the introduction of weight-based subcutaneous dosing of low molecular weight heparins (LMWH) represented a breakthrough by enabling more predictable, safer, and more convenient parenteral anticoagulation, particularly in the outpatient setting. More recently, direct oral anticoagulants (DOACs) have revolutionized clinical practice as they can be used in fixed doses without routine laboratory monitoring, thereby simplifying oral anticoagulation and are now preferred over VKAs for many indications. Unlike existing anticoagulants which suppress thrombin generation or inhibit factor Xa or thrombin, novel anticoagulants in development selectively target coagulation proteins within the contact activation pathway (such as Factor XI). These novel anticoagulants offer the potential to uncouple bleeding risk from antithrombotic efficacy and may also be effective for conditions in which clotting is driven by the contact activation pathway such as mechanical heart valves, for which DOACs are inadequate. However, their role and clinical indications remain to be defined in ongoing phase III trials.
A stepwise laboratory-based approach for early risk assessment of disseminated intravascular coagulation.
Zhou D, Wang J, Sun C … +2 more , Zhao Q, Chen L
Thromb Res · 2026 May · PMID 42320248 · Publisher ↗
BACKGROUND: Disseminated intravascular coagulation (DIC) is a life-threatening condition in which early identification is essential for timely clinical management. However, existing diagnostic approaches are often comple...
BACKGROUND: Disseminated intravascular coagulation (DIC) is a life-threatening condition in which early identification is essential for timely clinical management. However, existing diagnostic approaches are often complex. This study aimed to develop and validate a laboratory-based prediction model for early DIC risk assessment, while additionally evaluating different D-dimer interpretation strategies in relation to current diagnostic recommendations. METHODS: This single-center retrospective observational study consecutively included adult patients with overt disseminated intravascular coagulation (DIC) diagnosed between January 2015 and December 2024, together with individuals without DIC. An independent cohort from January to December 2025 was used for external validation. Ten routinely available coagulation and platelet-related biomarkers measured within 24 h prior to DIC diagnosis were analyzed. The diagnostic performance of D-dimer alone was evaluated using both the Chinese expert consensus cut-off strategy and the 2025 International Society on Thrombosis and Haemostasis (ISTH) upper limit of normal (ULN)-based classification. A multivariable prediction model was subsequently developed using routinely available laboratory parameters. RESULTS: A total of 2750 participants were included in the main cohort, with an additional 363 individuals in the external validation cohort. D-dimer interpreted using the ISTH ULN-based classification demonstrated better overall diagnostic performance than fixed cut-off strategies, with the >3 × ULN threshold providing the most balanced sensitivity and specificity. The final model incorporated four laboratory parameters-prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, and mean platelet volume (MPV)-and demonstrated strong discrimination, with areas under the receiver operating characteristic curve (AUCs) of 0.908 in the training cohort, 0.894 in the validation cohort, and 0.971 in the external validation cohort. Predicted risk showed a clear stepwise increase in DIC prevalence across risk strata. CONCLUSIONS: This four-parameter laboratory-based model provides an interpretable and externally validated tool for early DIC risk assessment using routinely available laboratory tests. The model may support preliminary risk stratification and facilitate timely clinical evaluation in patients at risk for DIC.
LY96-CCNT1-IFI44L core molecular features characterize VTE-associated inflammatory prothrombotic risk in elderly cancer patients.
Wu J, Hu B, Shao L … +5 more , Wang J, Wang Y, Wang L, Ju Y, Guo J
Thromb Res · 2026 Jun · PMID 42320247 · Publisher ↗
BACKGROUND: Venous thromboembolism (VTE) is an important complication in elderly patients with cancer, yet traditional clinical scoring systems insufficiently capture its molecular heterogeneity. This study aimed to cons...
BACKGROUND: Venous thromboembolism (VTE) is an important complication in elderly patients with cancer, yet traditional clinical scoring systems insufficiently capture its molecular heterogeneity. This study aimed to construct a VTE-related molecular risk stratification framework for elderly cancer patients, identify molecular features that remain stable across datasets, and clarify the potential inflammation-coagulation interaction mechanisms underlying high-risk states. METHODS: The peripheral-blood discovery cohort GSE19151 and the validation cohort GSE48000 from the Gene Expression Omnibus (GEO) database were integrated to identify stably differentially expressed genes (SDEGs). In The Cancer Genome Atlas (TCGA) elderly pan-cancer cohort, SDEGs and related pathway features were then used to construct a VTE-related molecular risk stratification framework. LASSO and random forest recursive feature elimination were applied for feature selection, multiple machine-learning models were compared, and SHAP analysis was used to evaluate feature contributions. GO/KEGG enrichment analysis, GSVA and weighted gene co-expression network analysis (WGCNA) were performed to characterize the biological basis of the high molecular-risk state. Kaplan-Meier analysis, time-dependent ROC curves and Cox regression were used to assess associations between the molecular risk score and prognosis. RESULTS: A total of 427 VTE-related differentially expressed genes were identified in the GSE19151 discovery cohort, and 38 SDEGs were retained after cross-cohort validation in GSE48000. Machine-learning analysis further identified 11 robust core features. Among them, LY96, CCNT1 and IFI44L showed dominant contributions in feature importance ranking, SHAP analysis and interaction analysis. Model comparison indicated that XGBoost and random forest achieved favorable classification performance. Functional enrichment analysis showed that SDEGs were mainly enriched in innate immunity, inflammatory responses, cytokine signaling and complement-coagulation-related processes. GSVA and WGCNA further revealed significant activation of complement-coagulation cascades, IL-6/JAK/STAT signaling and immune-inflammatory networks in the high VTE molecular-risk group. Survival analysis showed that the high-risk group had significantly poorer overall survival and progression-free interval, and the VTE molecular risk score retained independent prognostic value in multivariable Cox models. CONCLUSIONS: This study identified elderly cancer VTE-related core molecular features represented by LY96-CCNT1-IFI44L and established an interpretable molecular risk stratification framework. The framework highlights the coordinated activation of immune inflammation and coagulation pathways in high-risk states and provides a basis for evaluating VTE-related molecular heterogeneity and prognosis in elderly cancer patients.
Catheter-related thrombosis in oncology: A retrospective analysis of 803 long-term central venous catheters.
Pascoal M, Bernardo M, Caiado A … +5 more , Cabral F, Carvalhal S, Barroca R, Abecasis N, Oom R
Thromb Res · 2026 Jun · PMID 42320246 · Publisher ↗
Abstract loading — click title to view on PubMed.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe