Thrombosis Research[JOURNAL]
Sun
200 papers
Venous thrombosis in lung cancer compared with other tumors: results from the TESEO-SEOM registry.
Iglesias-Perez C, Jimenez-Fonseca P, López Robles J … +17 more , García Adrián S, Fernández Pérez I, Martínez Del Prado P, Rubio Pérez J, Martínez de Castro E, Díaz Pedroche C, García de Herreros M, Carmona Campos M, Rupérez Blanco AB, Salgado Fernández M, Quintanar Verdúguez T, Marrupe González D, Covela Rúa M, Santiago Crespo JA, Nieva Muñoz M, Muñoz A, Carmona-Bayonas A
Thromb Res · 2025 Dec · PMID 41237754 · Publisher ↗
BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a major adverse prognostic factor with heterogeneous outcomes across tumor types. We aimed to describe the characteristics of lung cancer patients with VTE, c...
BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a major adverse prognostic factor with heterogeneous outcomes across tumor types. We aimed to describe the characteristics of lung cancer patients with VTE, compare outcomes across malignancies, and assess their association with complications, progression, and survival. METHODS: We analyzed TESEO-SEOM, a prospective multicenter registry including patients with active cancer and VTE. Patients were stratified by tumor site, with lung as reference. Outcomes included recurrent VTE, bleeding, and survival. Analyses were stratified by tumor type and VTE presentation (clinically suspected, symptomatic/asymptomatic incidental). Complications were estimated using competing-risk methods. RESULTS: Among 3855 patients, the most frequent cancers were gastrointestinal (39.4 %), lung (22.2 %), and breast (10.4 %). Pulmonary embolism predominated (55 %), especially in lung cancer (69.8 %). Overall, 48.9 % of events were clinically suspected and 50.9 % incidental; suspected were more common in lung cancer (53.9 %), whereas incidental diagnoses predominated in gastrointestinal tumors (58.8 %). Complications occurred in 17.6 % (10.2 % bleeding, 7.4 % recurrent VTE). Recurrence was highest in gastrointestinal cancers (11.4 %, Gray's p = 0.022), while bleeding did not differ (p = 0.213). VTE-related mortality was low (1 %), while mixed-cause mortality was highest in lung cancer (17.2 %). Median PFS and OS were shortest in lung cancer (4.5 and 7.7 months, p < 0.0001). Incidental asymptomatic events conferred longer survival, particularly in lung cancer (OS 11.5 vs. 7.3 months for symptomatic incidental and 5.6 for suspected, p < 0.001). CONCLUSION: VTE in lung cancer is associated with more severe presentation, higher mixed-cause mortality, and worse survival than in other tumors. Incidental asymptomatic VTE predicts better outcomes, supporting risk stratification by tumor type and presentation.
Validation of the Japanese Association for Acute Medicine-2 disseminated intravascular coagulation criteria to predict critical bleeding in patients with trauma: A nationwide cohort study in Japan.
Takahashi M, Wada T, Tsuchida T … +4 more , Mori H, Umemura Y, Yamakawa K, Okamoto K
Thromb Res · 2025 Dec · PMID 41232203 · Publisher ↗
BACKGROUND: Trauma-induced coagulopathy (TIC) significantly impacts trauma prognosis, necessitating early intervention. The Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) crit...
BACKGROUND: Trauma-induced coagulopathy (TIC) significantly impacts trauma prognosis, necessitating early intervention. The Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria are one of the indicators for TIC, and modified criteria, JAAM-2 DIC criteria, have recently been proposed. We aimed to investigate the predictive ability of the JAAM-2 DIC criteria and its components for critical bleeding during the acute trauma phase. METHODS: This retrospective observational study used a nationwide Japanese database, including 2.7 million patients admitted between 2014 and 2023. We included adult inpatients transported by emergency medical services due to trauma. The JAAM-2 DIC scores on admission were calculated based on platelet count, prothrombin time-international normalized ratio (PT-INR), and fibrinogen/fibrin degradation products (FDP). The primary endpoint was critical bleeding, defined as a composite of death within 24-h or massive transfusion (receiving ≥10 units of red blood cells transfusion within 2 days). We investigated the relationship between the JAAM-2 DIC score, its components, and outcomes using the area under the receiver operating characteristic curve (AUC). RESULTS: Among the 10,834 patients with trauma, 1.7 % had critical bleeding. The JAAM-2 DIC score had an AUC of 0.802, with PT-INR showing the highest AUC of 0.836 among its components. The FDP score distribution was more irregular than the others, weakening the JAAM-2 DIC score's association with prognosis. CONCLUSION: The JAAM-2 DIC criteria can predict critical bleeding in trauma. Identifying and revising FDP scoring issues in JAAM-2 DIC criteria for trauma improved AUC for predicting critical bleeding.
Regenerating islet derived Family Member 4 (REG4) does not influence parameters of hemostasis in colorectal cancer.
Anijs RJS, Nguyen YN, Yanovska M … +7 more , van den Akker R, Laghmani EH, Ünlü B, Cannegieter SC, Buijs JT, Versteeg HH, Rondon AMR
Thromb Res · 2025 Dec · PMID 41232202 · Publisher ↗
BACKGROUND: Colorectal cancer (CRC) patients are at increased risk of developing venous thromboembolism (VTE), leading to high morbidity and mortality. The exact mechanism remains unknown, which complicates risk predicti...
BACKGROUND: Colorectal cancer (CRC) patients are at increased risk of developing venous thromboembolism (VTE), leading to high morbidity and mortality. The exact mechanism remains unknown, which complicates risk prediction and treatment. Previously, using RNA-sequencing, Regenerating islet derived Family Member 4 (REG4) was identified to be upregulated in tumor cells from CRC patients with VTE compared to tumor cells from CRC patients without VTE. OBJECTIVE: Here we aim to functionally validate the role of REG4 in cancer-associated thrombosis (CAT) using different in vitro tests of thrombosis and hemostasis. METHODS: Recombinant purified protein (rREG4), as well as REG4 overexpressing human colorectal cell lines were used to characterize the possible role of REG4. Prothrombin time (pT), activated partial thromboplastin time (aPTT) in normal pooled plasma (NPP) and whole blood and thrombin generation in NPP were determined in the presence of rREG4. In addition, the effect of rREG4 and RKO-REG4 expressing cells on plasma clot turbidity after exposure to human umbilical vein endothelial cell (HUVEC) was assessed by a turbidimetric assay, qPCR and Electric Cell-substrate Impedance Sensing (ECIS). In an organ-on-a-chip-model for cancer-associated hypercoagulability, RKO cells were co-cultured with vessel-forming HUVECs, after which thrombin generation was assessed. RESULTS: rREG4 did not alter pT and aPTT clotting times nor the thrombin generation potential in NPP and whole blood. Conditioned medium of RKO-REG4 secreting cells did not alter the thrombin generation potential, compared to the negative control (mock transfected RKO cells). In addition, no effect was observed on in vitro turbidimetric clot formation or on ECIS after endothelial cell stimulation. In line with this, using a cancer-associated hypercoagulability-on-a-chip model, RKO-REG4 cells did not further influence endothelial barrier integrity, nor thrombin generation potential, compared to control RKO cells. CONCLUSIONS: Extensive in vitro and microfluidic methods showed no effect of REG4 on coagulation parameters in CRC. Further research is needed into the mechanism behind CAT, as its understanding will help in better risk prediction and treatment.
The effects of pseudoserum on thrombin-induced fibrin networks: Potential for clinical insight into coagulation independent of traditional parameters.
Nunes M, Kruger A, Fielding B … +2 more , Kell DB, Pretorius E
Thromb Res · 2025 Dec · PMID 41232201 · Publisher ↗
Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormone...
Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organization, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organised architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. Furthermore, fibrinolysis was significantly reduced in the patient groups, demonstrating the ability of pseudoserum to influence the susceptibility of fibrin networks to plasmin-induced degradation. The ability of pseudoserum to drive these changes, despite the essential absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen's structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII's crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor-depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.
Platelet-related biomarkers and catheter-associated thrombosis in critically ill children: An exploratory study.
Regmi H, Li I, Prozora S … +4 more , Sharda A, Shabanova V, Faustino EVS, CRETE Trial and ATLAS Investigators
Thromb Res · 2025 Dec · PMID 41223722 · Full text
BACKGROUND: Platelets release different substances when activated, such as during critical illness when children are inflamed. We explored the associations of catheter-associated deep venous thrombosis (CADVT), clinicall...
BACKGROUND: Platelets release different substances when activated, such as during critical illness when children are inflamed. We explored the associations of catheter-associated deep venous thrombosis (CADVT), clinically relevant bleeding (CRB) and prophylactic enoxaparin with biomarkers of platelet activation and inflammation in critically ill children. METHODS: We analyzed platelet-poor plasma collected from critically ill children <18 years old with central venous catheter (CVC) enrolled in 2 multicenter studies conducted between 2017 and 2024. Blood was obtained on the day of, day after and 4 days after insertion of the CVC. Children were monitored daily for CRB and systematically surveilled for CADVT using ultrasonography. P-selectin, CD40L, platelet factor 4, RANTES, human thrombospondin 1, IL-1β, IL-2, IL-6, IL-8 and TNF-α were measured using immunosorbent assays. RESULTS: We studied plasma from 126 children (median: 9.6 years; interquartile range: 1.2, 15.3 years), of whom 24 received prophylactic enoxaparin. CADVT developed in 37.6 % and CRB in 31.0 % of children. Among children without prophylactic enoxaparin, CADVT was associated with high P-selectin and IL-6. A biomarker-augmented model with P-selectin and IL-6 seemed to perform better than a clinical model with age group, severity of illness and platelet count in identifying critically ill children with CADVT. CRB was associated with high platelet factor 4, while prophylactic enoxaparin was associated with high TNF-α. CONCLUSIONS: Our findings suggest the role of platelet activation in CADVT in critically ill children. Once confirmed, these biomarkers may be used to identify critically ill children who would benefit from pharmacologic prophylaxis.
αIIbβ3-dependent platelet procoagulant activity promotes pulmonary arterial thrombosis triggered by circulating tissue factor.
Tashbook SE, Kaminski TW, St Croix CM … +3 more , Watkins SC, Sundd P, Brzoska T
Thromb Res · 2025 Dec · PMID 41218268 · Full text
In situ pulmonary arterial thrombosis (iPAT), occurring without concurrent deep vein thrombosis, is a life-threatening complication associated with various pathological conditions. The etiological mechanisms underlying i...
In situ pulmonary arterial thrombosis (iPAT), occurring without concurrent deep vein thrombosis, is a life-threatening complication associated with various pathological conditions. The etiological mechanisms underlying iPAT remain poorly understood. Several studies suggest that circulating tissue factor (cTF) may contribute to the development of thrombotic complications; however, there is no direct in vivo evidence supporting the role of cTF in the pathogenesis of iPAT. Furthermore, although in vitro studies suggest that platelet anionic phospholipids enable cTF-initiated coagulation, how platelets contribute to cTF-dependent iPAT in vivo remains unknown. In the current study, we used quantitative fluorescence intravital lung microscopy to investigate the development of cTF-induced iPAT in live mice following intravascular administration of thromboplastin. To dissect the interplay between coagulation and platelet procoagulant activity, we assessed the effects of coagulation and platelet inhibition on iPAT development in vivo. Additionally, we conducted an in vitro clotting time assay using mouse plasma samples. Thromboplastin triggered iPAT in mice in a dose-dependent manner. IPAT involved the formation of platelet-rich thrombi at the bottle-neck junctions of pulmonary arterioles and capillaries, which was prevented by heparin. Notably, pretreatment of mice with annexin A5 or eptifibatide also completely abrogated thromboplastin-induced iPAT. These intravital microscopy findings were further corroborated by the in vitro clotting time assay. Our study provides in vivo evidence that cTF contributes to the development of iPAT. We demonstrate that the prothrombotic effect of cTF is dependent on platelet-αIIbβ3 signaling, which enhances platelet procoagulant activity, leading to accelerated coagulation and development of iPAT.
Association of anticoagulant therapy with bleeding in patients with chronic liver disease: A case-cross over study using the National Veterans Health Administration database.
Mahmoud A, Sanfilippo KM, Gage BF … +2 more , Luo S, Afzal A
Thromb Res · 2025 Dec · PMID 41218267 · Publisher ↗
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Bone marrow blasts- and modified EASIX-guided risk stratification for coagulopathy and outcomes after CAR-T therapy in relapsed/refractory B-ALL.
Li Y, Liu J, Luo L … +13 more , Zhou L, Wu Z, Sang W, Jiang H, Wang J, Wang X, Li P, Chen Z, Shu J, Luo W, Hu Y, Li Y, Mei H
Thromb Res · 2025 Dec · PMID 41218266 · Publisher ↗
BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While CAR-T-associated coagulopathy (CARAC) remains a...
BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While CAR-T-associated coagulopathy (CARAC) remains a critical complication, significantly increasing the risk of hemorrhage and disseminated intravascular coagulation (DIC). AIMS: To develop an effective CARAC risk stratification and outcome prediction model. METHODS: This multicenter retrospective study enrolled r/r B-ALL patients who received CD19 CAR-T therapy between January 2016 and July 2025. Machine learning, logistic regression and cutoff values were utilized to select key variables and develop predictive models. Model performance and clinical applicability were evaluated by receiver operating characteristic, calibration, and clinical decision curves. Survival analyses evaluated the impact of CARAC severity on overall survival (OS) and progression-free survival (PFS) and to validate the prognostic value of the prediction model. RESULTS: Bone marrow (BM) blasts and the modified endothelial activation and stress index (mEASIX) were independent predictors for CARAC. Patients with mEASIX<4.0 were identified as low-risk CARAC. For patients with mEASIX≥4.0, CARAC was stratified by BM blast percentage (blast%). Blast% between 10 % and 44 % indicated high-risk CARAC-nonDIC, and a blast% ≥ 44 % indicated high-risk CARAC-DIC. Moreover, compared to non-CARAC patients, CARAC patients had inferior OS (hazard ratio [HR]: 2.62, p = 0.002) and PFS (HR: 2.11, p = 0.002). The stratified prediction model revealed progressively worse OS and PFS from low-risk CARAC patients to high-risk CARAC-nonDIC, with high-risk CARAC-DIC patients demonstrating the most unfavorable outcomes. CONCLUSIONS: An effective CARAC risk prediction and stratification model was established. High-risk CARAC patients, particularly CARAC-DIC, were associated with significantly worse outcomes.
In vitro anticoagulant effect of nafamostat mesylate in andexanet-induced heparin resistance.
Okada H, Mishima Y, Bouvette SM … +3 more , Jang MUK, Tanaka KA, Butt AL
Thromb Res · 2025 Dec · PMID 41205397 · Publisher ↗
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A novel F7 mutation (p.Gly217Arg) associated with infantile intracranial hemorrhage successfully managed with rFVIIa.
Ozay M, Gumus U, Ünal E
Thromb Res · 2025 Dec · PMID 41202584 · Publisher ↗
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Three new variants of the fibrinogen-related domain of the fibrinogen Bβ chain.
Kotlín R, Sovová Ž, Sklenářová T … +5 more , Havlíček M, Suttnar J, Chrastinová L, Hrachovinová I, Hlaváčková A
Thromb Res · 2025 Dec · PMID 41176834 · Publisher ↗
INTRODUCTION: Variants in genes coding fibrinogen chains may lead to a quantitative fibrinogen disorder-hypofibrinogenemia. The aim of the study was to determine the cause of congenital hypofibrinogenemia and characteriz...
INTRODUCTION: Variants in genes coding fibrinogen chains may lead to a quantitative fibrinogen disorder-hypofibrinogenemia. The aim of the study was to determine the cause of congenital hypofibrinogenemia and characterize the underlying structure and function of fibrinogen. METHODS: Genetic and proteomic analyses were performed to determine fibrinogen variants and detect their presence in plasma. Scanning electron microscopy was used to study fibrin clot morphology, and polymerization experiments were used to determine its effect on fibrin formation. Bioinformatics and in silico structural biology techniques were used to predict the impact of variant on the protein's stability and function. RESULTS: We identified three previously undescribed variants of the fibrinogen-related domain (FReD) of the fibrinogen Bβ chain-FGB:p.Asp350His, FGB:p.Arg436Lys, and FGB:p.Tyr447Cys. Fibrin structure and fibrin polymerization were very slightly affected in FGB:p.Asp350His and FGB: p.Arg436Lys cases. The FGB:p.Tyr447Cys variant could have physiological manifestations because it destabilizes the binding site of the fibrinogen Bβ chain. The FGB:Arg436Lys variant does not destabilize the protein's structure, but it may disturb fibrin polymerization. High conservation of Arg436 may indicate its importance in fibrinogen biosynthesis or secretion. FGB:p.Asp350His is situated in the N-terminal residue of the third β-strand of the central antiparallel β-sheet of the FReD, forming a hydrogen bond with Asp346, and Asp350 seems to have a negligible effect on the formation of the correct Bβ chain structure. CONCLUSION: The analyzed variants in the FReD of the fibrinogen Bβ chain seems to have an impact on the proper structure of the fibrinogen-related domain of the fibrinogen Bβ chain.
Contemporary reperfusion therapies in patients with intermediate- and high-risk pulmonary embolism.
Shen BH, Shankar DA, Bosch NA … +4 more , Walkey AJ, Piazza G, Klings ES, Law AC
Thromb Res · 2025 Dec · PMID 41175547 · Full text
BACKGROUND: Without clear guidelines, contemporary use of reperfusion therapy for intermediate-risk and high-risk pulmonary embolism (PE) may vary widely. We assessed variation and trends in use of reperfusion therapies...
BACKGROUND: Without clear guidelines, contemporary use of reperfusion therapy for intermediate-risk and high-risk pulmonary embolism (PE) may vary widely. We assessed variation and trends in use of reperfusion therapies (systemic thrombolysis, catheter-directed thrombolysis, mechanical thrombectomy) and how practices change when hospitals adopt mechanical thrombectomy. METHODS: Using the national Premier Inc. AI Database (2016-2022), we identified adults with intermediate-risk or high-risk PE. For each reperfusion therapy, our primary outcome was intraclass correlation coefficient (ICC, representing between-hospital variation unexplained by patient/hospital characteristics; a priori, ICC > 15 % deemed "high" variation) and proportion trends over time with hierarchical regression models and assessed trends in use. Among hospitals that adopted mechanical thrombectomy, we conducted interrupted time series analysis to assess changes in use of systemic thrombolysis, catheter-directed thrombolysis, and any reperfusion therapy. RESULTS: We assessed 13,777 patients (11,846 intermediate-risk; 1931 high-risk PE) admitted in the US between 2016 and 2022. High variation was observed in catheter-directed thrombolysis (intermediate-risk: ICC 23.1 %; high-risk: ICC 23.8 %) and thrombectomy use (intermediate-risk: ICC 35.4 %; high-risk: ICC 25.1 %). Mechanical thrombectomy use increased from 0.6 % to 14.3 % between 2016 and 2022 (p < 0.001). Hospital adoption of mechanical thrombectomy was associated with a deceleration in growth of catheter-directed thrombolysis rates. CONCLUSIONS: Among patients with intermediate-risk and high-risk PE in the US, reperfusion therapy use varies widely, and the use of mechanical thrombectomy increased between 2016 and 2022. At hospitals adopting mechanical thrombectomy, thrombectomy supplants catheter-directed thrombolysis without increasing total use of reperfusion therapy. These results raise questions about standardization of care, optimal resource allocation, and impact on patient outcomes.
Systematic review of a machine learning model for prediction of venous thromboembolism risk.
Ge WJ, Zhu TF, Ge WJ … +2 more , Zhu XY, Chu AQ
Thromb Res · 2025 Dec · PMID 41175546 · Publisher ↗
OBJECTIVE: This systematic review aims to evaluate the methodological quality, performance, and clinical applicability of machine learning (ML) models for predicting the risk of venous thromboembolism (VTE) in hospitaliz...
OBJECTIVE: This systematic review aims to evaluate the methodological quality, performance, and clinical applicability of machine learning (ML) models for predicting the risk of venous thromboembolism (VTE) in hospitalized patients. Specifically, we aim to assess the methodological quality and reporting transparency of the included studies, with a focus on their risk of bias and adherence to reporting guidelines. METHODS: A systematic review by use of the databases Cochrane Library, Web of Science, Embase, PubMed, CNKI, VIP Journal Database, Wanfang Database, and the Chinese Biomedical Literature Database. The study was registered at PROSPERO before data collection and PRISMA guidelines were followed. The search was conducted to identify all relevant studies published from the inception of database up to August 1, 2024. Two independent researchers screened the literature and extracted data. Model quality was assessed using the PROBAST appraisal tool and a modified TRIPOD+AI framework, alongside reported model performance metrics. RESULTS: A total of seventeen studies were included, comprising 65 VTE ML models with sample sizes ranging from 120 to 9213. All models demonstrated an area under the curve (AUC) >0.7. Twenty-three ML algorithms were employed, with logistic regression (LR) being the most frequently used (n = 11), followed by XGBoost (n = 10) and random forests (RF) (n = 9). Thirteen studies utilized various stochastic algorithms. Most studies used Bootstrap or 10-fold cross-validation for internal validation, but lacked external validation, leading to a high overall risk of bias. Key predictors in these models included D-dimer, history of thrombosis, history of hypertension, age, and complications. CONCLUSIONS: Existing evidence suggests that ML models can effectively predict VTE outcomes. However, most models suffer from poor methodological quality, lack of external validation, and limited generalizability. Future research should focus on large-scale, multi-center prospective studies that are based on clinical practice, improve external validation, and develop optimized local VTE risk assessment and decision support tools for better integration into clinical practice.
Predictive value of the systemic immuane-inflammation index for deep vein thrombosis: A meta-analysis.
Chen X, Mao Y, Ge Y … +1 more , Ju D
Thromb Res · 2025 Dec · PMID 41172591 · Publisher ↗
OBJECTIVE: The systemic immune-inflammation index (SII), a new inflammatory marker, is considered a predictive indicator for multiple malignant tumors and inflammatory illnesses. Its relationship with deep vein thrombosi...
OBJECTIVE: The systemic immune-inflammation index (SII), a new inflammatory marker, is considered a predictive indicator for multiple malignant tumors and inflammatory illnesses. Its relationship with deep vein thrombosis (DVT) has garnered growing attention. This research seeks to systematically examine the relationship between SII and DVT. METHODS: Embase, Web of Science, Cochrane Library, and PubMed were searched up to January 6, 2025, for observational studies examining the link between SII and DVT. Two reviewers separately screened the retrieved articles, extracted data, and appraised the quality of the enrolled studies. MetaDisc version 1.4 and StataMP 15 were utilized to carry out statistical analyses. RESULTS: 14 studies involving 13,655 individuals were included. The meta-analysis demonstrated that individuals with DVT exhibited elevated SII in comparison to those without DVT (WMD = 938.60; 95 % CI: 466.55-1410.64; p < 0.001). Moreover, individuals with elevated SII had a 4.73-fold greater risk of DVT than those with low SII (95 % CI: 2.19-10.19; p < 0.001). The pooled diagnostic performance revealed a specificity of 78 % (95 % CI: 71 %-84 %), sensitivity of 69 % (95 % CI: 56 %-79 %), negative likelihood ratio of 0.40 (95 % CI: 0.26-0.60), positive likelihood ratio of 3.18 (95 % CI: 2.12-4.76), and diagnostic odds ratio of 7.96 (95 % CI: 3.66-17.30). The area under the receiver operating characteristic curve was 0.81 (95 % CI: 0.77-0.84). Sensitivity analyses were carried out by sequentially excluding individual studies, and no substantial changes were observed in the mean differences, odds ratios, or diagnostic estimates, indicating the stability of the results. No substantial publication bias was detected in the analyses of mean differences, odds ratios, or diagnostic measures. CONCLUSION: Elevated SII is related to a higher likelihood of DVT, suggesting its potential as a valuable predictor of DVT risk.
The role of platelets in the regulation of myeloid-derived suppressor cells in immune thrombocytopenia.
Moghaddasnejad MR, Sherafat NS, Saki N
Thromb Res · 2025 Dec · PMID 41138350 · Publisher ↗
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune regulatory cells that play crucial roles in suppressing immune responses and promoting immune tolerance in autoimmune diseases. Platelets, hist...
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune regulatory cells that play crucial roles in suppressing immune responses and promoting immune tolerance in autoimmune diseases. Platelets, historically recognized for their role in hemostasis, have recently attracted significant attention for their immune regulatory functions, mainly through their interactions with immune cells, including MDSCs. In patients with immune thrombocytopenia (ITP), both the quantity and suppressive function of MDSCs are decreased. However, following treatment and subsequent elevation of platelet counts, the mean level and suppressive capacity of MDSCs increase. Studies have indicated that platelet-derived products can increase the suppressive capacity of MDSCs in ITP, thereby promoting immune tolerance and reducing inflammation. Conversely, specific platelet-secreted molecules such as TGF-β and histamine play complex roles and are capable of both augmenting and inhibiting MDSC activity, depending on the context. Understanding these interactions reveals potential targets in platelet-MDSC signaling pathways as novel approaches for ITP management. Future research could investigate targeted therapies that modulate MDSC function by enhancing or inhibiting specific platelet-derived mediators, leading to the development of innovative treatments for autoimmune diseases such as ITP.
Management of venous thromboembolism in stroke: A deep appraisal exposing discordance in guideline quality and recommendations.
Li HY, Wang HS, Wang J … +3 more , Wang YH, Jiang SL, Wang LH
Thromb Res · 2025 Dec · PMID 41135230 · Publisher ↗
BACKGROUND: This study assessed clinical practice guidelines (CPGs) for venous thromboembolism (VTE) prophylaxis and treatment in patients with stroke to provide evidence-based reference for clinicians. METHODS: We syste...
BACKGROUND: This study assessed clinical practice guidelines (CPGs) for venous thromboembolism (VTE) prophylaxis and treatment in patients with stroke to provide evidence-based reference for clinicians. METHODS: We systematically identified CPGs published between January 1, 2020 and January 1, 2025. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) and the Appraisal of Guidelines for Research and Evaluation-Recommendation Excellence (AGREE-REX) instruments were utilized to evaluate the quality of methodology and recommendations, respectively. Prophylaxis and treatment recommendations for VTE were extracted and compared for consistency and divergence. RESULTS: 12 CPGs were included. The median (interquartile range [IQR]) scores for AGREE II six domains were: scope and purpose, 85.4 % (9.0 %); stakeholder involvement, 63.2 % (29.9 %); rigour of development, 65.4 % (18.5 %); clarity of presentation, 84.7 % (4.9 %); applicability, 49.5 % (33.3 %); and editorial independence, 76.0 % (41.7 %). The AGREE-REX assessment results were as follows: clinical applicability, 68.8 % (25.4 %); values and preferences, 19.3 % (20.6 %); and implementability, 36.5 % (9.4 %). Analysis of 64 key recommendations showed consistent support for intermittent pneumatic compression but not graduated compression stockings. Pharmacological prophylaxis remains controversial across both ischemic and hemorrhagic stroke. CONCLUSION: Current stroke VTE guidelines demonstrate strengths in scope and clarity, but critical limitations in applicability and values and preferences. Although consensus on mechanical prophylaxis is clear, evidence for pharmacological prevention remains controversial. Future guideline development must enhance methodological rigour and address these critical evidence gaps through targeted primary research. This study provides a foundational synthesis of evidence-based insights to inform both clinical decision-making and the development of more applicable, trustworthy guidelines.
Assessing the risk of venous thromboembolism in trans masculine persons on gender-affirming hormone therapy: A literature review.
Hugueny J, de Ricolfis A, Johnson N … +2 more , Chabbert-Buffet N, Cristofari S
Thromb Res · 2025 Dec · PMID 41135229 · Publisher ↗
OBJECTIVE: This review aimed to synthesize recent data on venous thromboembolism (VTE) risk in the context of masculinizing hormone therapy with testosterone. METHODS: An electronic search was performed in MEDLINE/PubMed...
OBJECTIVE: This review aimed to synthesize recent data on venous thromboembolism (VTE) risk in the context of masculinizing hormone therapy with testosterone. METHODS: An electronic search was performed in MEDLINE/PubMed without date restrictions. Eligible articles were peer-reviewed observational and interventional studies and had to be written in English. Results are presented by theme of analysis. RESULTS: Most recent large-scale studies investigating trans masculine populations have not found a statistically significant change in the risk of VTE. However, most of the available data relate to younger individuals with minimal cardiovascular risk factors. For patients with a personal or family history of VTE, the introduction of testosterone therapy should be discussed within a multidisciplinary team specializing in transgender health, balancing the risk-benefit ratio in a population where the risk of suicide is high and is largely reduced by gender-affirming hormone therapy. CONCLUSIONS: Most of the studies did not found a significant change in the risk of venous thromboembolism in trans masculine persons taking testosterone. However, data are limited, and further robust studies are warranted to clarify these data and to generalize these results to higher veinous thromboembolic risk groups.
Prothrombotic profiles in myelofibrosis: Fibrinogen oxidation and the beneficial effects of ruxolitinib.
Nencini F, La Spina E, Borghi S … +11 more , Giurranna E, Argento FR, Fini E, Giallongo C, Duminuco A, Volti GL, Palumbo GA, Taddei N, Fiorillo C, Tibullo D, Becatti M
Thromb Res · 2025 Dec · PMID 41135228 · Publisher ↗
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, bone marrow fibrosis, extramedullary hematopoiesis and aberrant inflammation. About 90 % of MF patients ca...
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, bone marrow fibrosis, extramedullary hematopoiesis and aberrant inflammation. About 90 % of MF patients carry mutations in JAK2, CALR, or MPL, with JAK2 mutations promoting cytokine independence, STAT proteins activation and enhances reactive oxygen species (ROS) production. Inflammation and oxidative stress are key contributors to thrombotic risk, a major cause of morbidity and mortality in MF. Fibrinogen, a key factor in coagulation and inflammation, may play a central role due to its susceptibility to oxidative modifications. In particular, in MPN patients, impaired fibrinolysis associated with endothelial cell dysfunction, increased ROS and proinflammatory cytokines production have been reported. This study investigates the role of oxidation-induced structural and functional changes in fibrinogen in MF patients compared to healthy controls, also analyzing the effects of ruxolitinib, a first-in-class JAK inhibitor. Plasma samples from 15 untreated MF patients, 39 ruxolitinib-treated MF patients, and 40 matched healthy controls were analyzed for redox status and fibrinogen properties. MF patients showed elevated plasma lipid peroxidation and nitrate/nitrite levels, reduced antioxidant capacity, and lower free thiol content. These changes were associated with significant fibrinogen oxidation, leading to structural alterations and impaired function, including reduced fibrin polymerization and decreased plasmin-mediated fibrinolysis. Strong correlations were observed between oxidative stress markers and fibrinogen dysfunction. Treatment with ruxolitinib improved redox balance and restored fibrinogen structure and function. These findings provide the first evidence of a prothrombotic profile in MF patients, driven by structural and functional fibrinogen modifications.
MicroRNA dynamics and their link to platelet function following acute ST-segment elevation myocardial infarction.
Pedersen OB, Grove EL, Kristensen SD … +3 more , Pasalic L, Hvas AM, Nissen PH
Thromb Res · 2025 Dec · PMID 41129894 · Publisher ↗
BACKGROUND: Reduced effect of antiplatelet therapy has been observed in patients with ST-segment elevation myocardial infarction (STEMI). MicroRNA (miR) expression may serve as biomarkers for platelet function and the ef...
BACKGROUND: Reduced effect of antiplatelet therapy has been observed in patients with ST-segment elevation myocardial infarction (STEMI). MicroRNA (miR) expression may serve as biomarkers for platelet function and the effect of antiplatelet therapy. AIM: In acute STEMI patients, we investigated changes in miR expression from the acute event to a more stable phase, and evaluated their association with platelet function at both time points to assess their potential as biomarkers of antiplatelet therapy efficacy. METHODS: Patients admitted with acute STEMI for primary percutaneous coronary intervention were included and treated according to guidelines. Samples were collected within 24 h after admission and at 2-3 months after enrolment. Expression of candidate miRs, platelet reactivity markers evaluated by flow cytometry, platelet impedance aggregometry and serum thromboxane B were measured at both time points. RESULTS: Samples were obtained in 44 STEMI patients. Two miRs (miR-15a-5p and miR-21-5p) showed lower, whereas five (miR-26b-5p, miR-126-3p, miR-150-5p, miR-223-3p and miR-423-5p) showed higher expression at follow-up than at baseline. At baseline, miR-26b-5p expression consistently correlated with the expression of the fibrinogen receptor on activated platelets, across different agonists (rho: from 0.29 to 0.32, p < 0.05). At follow-up, miR-93-5p expression was associated with platelet aggregation using various agonists (rho: from -0.39 to -0.47, p < 0.02). CONCLUSIONS: Seven miRs were differentially expressed at follow-up compared to baseline. Several miRs were linked to platelet function at baseline and follow-up, suggesting that a single miR may not be sufficient as a biomarker for platelet function and the effect of antiplatelet therapy.
Reduced-dose versus full-dose apixaban for extended treatment of cancer-associated venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.
Crichi B, Delrue M, Alsuliman T … +2 more , Le Jeune S, Frere C
Thromb Res · 2025 Dec · PMID 41110368 · Publisher ↗
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