Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Beyond hemostasis, the immunomodulatory nature of platelets","authors":"Wanting Wang ,&nbsp;Chaofan Wang ,&nbsp;Jun Deng ,&nbsp;Bahgat Fayed ,&nbsp;Desheng Hu ,&nbsp;Heng Mei ,&nbsp;Yu Hu ,&nbsp;Shanshan Luo","doi":"10.1016/j.rpth.2025.103182","DOIUrl":"10.1016/j.rpth.2025.103182","url":null,"abstract":"<div><div>In addition to playing a key role in hemostasis, platelets are involved in immunomodulatory processes against pathogenic infection. Platelets secrete substances and express membrane proteins that form part of the immune defense environment to effectively remove pathogens. Direct or indirect contact of pathogens with platelets can activate platelets, which subsequently elicit a range of immune responses <em>in vivo</em>, leading to pathogen clearance, evasion, or tissue damage. This review summarizes the immune functions of platelets beyond hemostasis, their interactions with other immune components such as the complement system, neutrophils, and monocytes, and specifically highlights the immune effects exerted by platelets against several microbial infections.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 7","pages":"Article 103182"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total and extracellular vesicle–bound plasma P-selectin as diagnostic biomarkers for acute deep vein thrombosis","authors":"Samantha Xavier ,&nbsp;Vårin Eiriksdatter Wikan ,&nbsp;Casper J.E. Wahlund ,&nbsp;Nadezhda Latysheva ,&nbsp;Øyvind Øverli ,&nbsp;Christopher Antoun ,&nbsp;Thor Ueland ,&nbsp;Gholamreza Jafari Yeganeh ,&nbsp;Sigrid Kufaas Brækkan ,&nbsp;John-Bjarne Hansen ,&nbsp;Ellen Brodin ,&nbsp;Omri Snir","doi":"10.1016/j.rpth.2025.103171","DOIUrl":"10.1016/j.rpth.2025.103171","url":null,"abstract":"<div><h3>Background</h3><div>Plasma P-selectin has shown moderate diagnostic potential for deep vein thrombosis (DVT). In plasma, P-selectin is found in soluble form and bound to extracellular vesicles (EVs). It is unknown whether specific detection of EV-bound P-selectin would improve the diagnostic performance of P-selectin. We aimed to investigate the diagnostic performance of EV-bound and total P-selectin for acute DVT, alone and in combination with D-dimer.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the diagnostic potential of total extracellular vesicle-bound plasma P-selectin as diagnostic biomarkers for acute deep vein thrombosis in a cohort of patients admitted to hospital with suspected DVT.</div></div><div><h3>Methods</h3><div>A bead-based flow cytometric assay was developed for selective detection of EV-bound P-selectin. Total and EV-bound P-selectin was measured in 2 cohorts of patients (<em>n</em> = 168 and <em>n</em> = 200) referred to hospital with suspected DVT. DVT was confirmed or ruled out by compression ultrasound.</div></div><div><h3>Results</h3><div>DVT was confirmed in 53 patients and ruled out in 115 patients (first cohort) and in 54 and 146 patients (replication cohort), respectively. Only 2% of plasma P-selectin was bound to EVs, and EV-bound P-selectin showed poor diagnostic performance with an area under the receiver-operating characteristic curve (AUC) of 0.55 (95% CI, 0.45-0.65). Total plasma P-selectin had an AUC of 0.70 (95% CI, 0.62-0.78) in the first cohort and 0.77 (95% CI, 0.69-0.85) in the replication cohort. Combination of total P-selectin with D-dimer had diagnostic performance (AUC, 0.88; 95% CI, 0.84-0.91) inferior to D-dimer alone (AUC, 0.92; 95% CI, 0.89-0.95).</div></div><div><h3>Conclusion</h3><div>The proportion of P-selectin bound to EVs in plasma was low and could not discriminate between patients with and without acute DVT. The diagnostic performance of total P-selectin, alone or in combination with D-dimer, was inferior to the diagnostic performance of D-dimer alone.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 7","pages":"Article 103171"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High- and intermediate-risk pulmonary embolism in pediatric tertiary care centers in the Netherlands","authors":"C.A.M. (Karlijn) van Balkom ,&nbsp;Irene L.M. Klaassen ,&nbsp;Marije Diender ,&nbsp;Idske Kremer Hovinga ,&nbsp;Marjet A. Stein-Wit ,&nbsp;Frans J.W. Smiers ,&nbsp;C. Heleen van Ommen","doi":"10.1016/j.rpth.2025.102972","DOIUrl":"10.1016/j.rpth.2025.102972","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary embolism (PE) response teams are increasingly used in adult care to improve severe PE management. Understanding the epidemiology, treatment, and outcomes of severe PE in children is crucial to assessing the need for pediatric PE response teams in the Netherlands.</div></div><div><h3>Objectives</h3><div>To evaluate the incidence, management, and short-term outcomes of severe PE in Dutch pediatric patients.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included children (0-18 years) diagnosed with high- and intermediate-risk PE between 2012 and 2022 across 6 pediatric tertiary care centers in the Netherlands.</div></div><div><h3>Results</h3><div>Among 172 PE patients, 17 (10%) had high-risk PE and 19 (11%) had intermediate-risk PE. The annual PE incidence was estimated at 1.0 case per million children, predominantly affecting adolescents. Common symptoms included dyspnea (90%) and tachypnea (75%). Major risk factors were oral contraceptive use (57%) and congenital thrombophilia (39%). In the high-risk group, 100% underwent reperfusion therapy, including systemic thrombolysis (<em>n</em> = 13), surgical thrombectomy (<em>n</em> = 3), and catheter-directed therapy (CDT; <em>n</em> = 1). Four systemic thrombolysis failures required further intervention (3 CDT and 1 surgical thrombectomy). Major bleeding occurred in 2 patients (12%), and 2 (12%) suffered PE-related deaths. Among intermediate-risk patients, 42% received reperfusion therapy (7 systemic thrombolysis and 1 CDT), with major bleeding in 2 (11%) and no deaths. Postdischarge treatment included low-molecular-weight heparin (<em>n</em> = 10), vitamin K antagonists (<em>n</em> = 7), and direct oral anticoagulants (<em>n</em> = 17).</div></div><div><h3>Conclusion</h3><div>Severe PE is rare in Dutch children. The variation in indications and reperfusion strategies highlights the need for national, multidisciplinary care pathways to standardize management and improve outcomes.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 102972"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the interference of fitusiran and antithrombin lowering in plasma on routine coagulation assays","authors":"Ekta Seth Chhabra ,&nbsp;Mingjie Liu","doi":"10.1016/j.rpth.2025.102989","DOIUrl":"10.1016/j.rpth.2025.102989","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 102989"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emicizumab utilization, safety, and outcomes in people with severe hemophilia and no inhibitors: 3-year follow-up. A report from the UK Haemophilia Centre Doctors’ Organisation","authors":"Caroline Wall ,&nbsp;Hua Xiang ,&nbsp;Ben Palmer ,&nbsp;Pratima Chowdary ,&nbsp;Peter W. Collins ,&nbsp;Richard Gorman ,&nbsp;Mary Matthias ,&nbsp;Charles Percy ,&nbsp;Paul Sartain ,&nbsp;Susan Shapiro ,&nbsp;David Stephensen ,&nbsp;Kate Talks ,&nbsp;Charles R.M. Hay ,&nbsp;UK Haemophilia Centre Doctors’ Organisation (UKHCDO)","doi":"10.1016/j.rpth.2025.103164","DOIUrl":"10.1016/j.rpth.2025.103164","url":null,"abstract":"<div><h3>Background</h3><div>Emicizumab prophylaxis is restricted to severe hemophilia A in the UK. Treatment choice and safety remain a matter of debate.</div></div><div><h3>Objectives</h3><div>This study was conducted to investigate factors influencing treatment choice, continued use, safety, and clinical outcomes associated with emicizumab in a national cohort of persons with severe hemophilia A without current inhibitors.</div></div><div><h3>Methods</h3><div>A 3-year study was conducted in 618 persons with severe hemophilia A who switched to emicizumab and 413 who continued factor (F)VIII prophylaxis. Outcome measures included annualized bleed rates (ABRs), the Hemophilia Joint Health Score, and health-related quality of life.</div></div><div><h3>Results</h3><div>Switchers and nonswitchers had a similar median age (26 and 28 years, respectively). Switchers had a significantly higher median (IQR) ABR than those continuing FVIII prophylaxis, but a significantly lower proportion had an inhibitor history (13.6% vs 20.5%; <em>P</em> = .0005). Thirty-one adverse events were reported, including 1 thrombosis (0.2%), 8/84 recurrent inhibitors (9.5%), 1 neutralizing antidrug antibody (0.2%), and 14/618 (2.3%) patients discontinued emicizumab. A higher prestudy median (IQR) ABR was observed in switchers compared with nonswitchers (2.05 [0.43, 6.06] vs 0.68 [0, 2.7]), reducing to a median (IQR) of 0 (0, 0) with emicizumab prophylaxis. The proportion with a zero-treated bleed rate increased from 35% to 71% (<em>P</em> = .001). An 82% reduction in bleeding into target joints was observed in favor of emicizumab. A modest (Δ= −2; <em>P</em> = .02) improvement in the total Hemophilia Joint Health Score was observed.</div></div><div><h3>Conclusions</h3><div>Emicizumab selection was influenced by ABR and inhibitor history but not age. Emicizumab was generally well tolerated, with only 2.3% discontinuing the drug. A significant within-person improvement in all bleeding outcomes was observed with emicizumab.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 103164"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of clopidogrel and ticagrelor in acute coronary syndrome patients with CYP2C19 loss-of-function alleles after percutaneous coronary intervention: based on the Global Registry of Acute Coronary Events score","authors":"Dan Dang ,&nbsp;Jing Li ,&nbsp;Yi Li ,&nbsp;Miaohan Qiu ,&nbsp;Bin Wang ,&nbsp;Bin Qi ,&nbsp;Yaling Han","doi":"10.1016/j.rpth.2025.102997","DOIUrl":"10.1016/j.rpth.2025.102997","url":null,"abstract":"<div><h3>Background</h3><div>The selection of P2Y12 inhibitors for acute coronary syndrome patients after percutaneous coronary intervention (PCI) remains controversial among East Asian patients.</div></div><div><h3>Objectives</h3><div>This study aimed to identify the optimal P2Y12 inhibitor selection for the East Asian population carrying <em>CYP2C19</em> loss-of-function (LOF) alleles based on the Global Registry of Acute Coronary Events (GRACE) score.</div></div><div><h3>Methods</h3><div>Between March 2016 and March 2019, a cohort of 8683 patients diagnosed with acute coronary syndrome who survived PCI were enrolled in this study. All patients carried the LOF allele and could calculate GRACE scores. The primary outcome was ischemic events (cardiac death, nonfatal myocardial infarction, and ischemic stroke) within 12 months. Secondary outcomes included the components of the primary outcome, all-cause mortality, Bleeding Academic Research Consortium (BARC) types 2, 3, and 5 bleeding events, and BARC types 3 and 5 bleeding events. The propensity score matching method was used to balance the baseline characteristics of patients. The Kaplan–Meier/log-rank test was adopted for the result analysis, and Cox regression was employed for adjusting for confounding factors.</div></div><div><h3>Results</h3><div>The low-risk group comprised 5496 patients (63.3%), while the intermediate- to high-risk group included 3187 patients (36.7%) in the study population stratified by GRACE scores. The follow-up results revealed that in patients at low risk, clopidogrel and ticagrelor had comparable effects in preventing ischemic events. However, ticagrelor use was associated with a higher risk of BARC types 2, 3, and 5 bleeding events (hazard ratio [HR], 2.08; 95% CI, 1.43-3.02; <em>P</em> &lt; .001) and BARC types 3 and 5 bleeding events (HR, 2.69; 95% CI, 1.57-4.63; <em>P</em> &lt; .001) compared with clopidogrel use. In patients at intermediate to high risk, ticagrelor treatment was associated with a lower risk of stroke (HR, 0.18; 95% CI, 0.04-0.82; <em>P</em> = .026), while the risk of ischemic events or bleeding was comparable between the 2 treatment groups.</div></div><div><h3>Conclusion</h3><div>These real-world data on East Asian patients with <em>CYP2C19</em> LOF alleles suggest that GRACE risk stratification may help differentiate ischemic and bleeding risks post-PCI.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 102997"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of a new commercial assay for the measurement of tissue factor activity of extracellular vesicles isolated from human plasma","authors":"Ana T.A. Sachetto ,&nbsp;Alan E. Mast ,&nbsp;Nigel Mackman","doi":"10.1016/j.rpth.2025.103007","DOIUrl":"10.1016/j.rpth.2025.103007","url":null,"abstract":"<div><h3>Background</h3><div>Tissue factor (TF)-positive extracellular vesicles (EVs) are released into the circulation and activate coagulation in several diseases, such as sepsis, viral infections, and cancer.</div></div><div><h3>Objectives</h3><div>We compared a new commercial assay, called “CY-QUANT MV-TF” (CY), with an in-house assay (Chapel Hill [CH]) for the measurement of EV TF activity.</div></div><div><h3>Methods</h3><div>TF-positive EVs were generated by stimulating citrated human whole blood from 4 healthy donors with lipopolysaccharide for 5 hours. EVs were isolated from platelet-low plasma by centrifugation at 20,000 × <em>g</em> for 60 minutes at 4 °C.</div></div><div><h3>Results</h3><div>Lower levels of EV TF activity were detected in the samples using the CY assay compared with the CH assay (mean ± SD, 0.54 ± 0.30 pg/mL, <em>n</em> = 4 vs 1.59 ± 0.43 pg/mL, <em>n</em> = 4; <em>P</em> = .01). Interestingly, the CY assay used a lower ratio of plasma to wash buffer compared with the CH assay for EV isolation. This led to higher levels of TF pathway inhibitor (TFPI) in EVs isolated using the CY protocol compared with the CH protocol. Importantly, the addition of an inhibitory anti-TFPI antibody increased EV TF activity in both assays and eliminated the difference in EV TF activity between the 2 assays.</div></div><div><h3>Conclusion</h3><div>In this study, we found that the CY assay detected TF activity in EVs isolated from plasma. However, significant amounts of TFPI were present in the EV preparations using the CY EV isolation protocol, which inhibited TF activity, leading to lower apparent EV TF levels.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 103007"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in quality of vitamin K antagonist treatment and clinical outcomes during Ramadan: a Dutch population-based cohort study","authors":"Eva K. Kempers ,&nbsp;Qingui Chen ,&nbsp;Nienke van Rein ,&nbsp;Ferdows Atiq ,&nbsp;Roger K. Schindhelm ,&nbsp;Nynke M. Wiersma ,&nbsp;Charlotte E.A. Dronkers ,&nbsp;Maarten Beinema ,&nbsp;Arina J. ten Cate-Hoek ,&nbsp;Melchior C. Nierman ,&nbsp;Alexander D.M. Stork ,&nbsp;Patricia Moriarty ,&nbsp;Frederikus A. Klok ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Marieke J.H.A. Kruip","doi":"10.1016/j.rpth.2025.103010","DOIUrl":"10.1016/j.rpth.2025.103010","url":null,"abstract":"<div><h3>Background</h3><div>Ramadan fasting alters the timing and content of food, including dietary vitamin K, and medication intake, potentially affecting stability of vitamin K antagonist (VKA) treatment and clinical outcomes.</div></div><div><h3>Objectives</h3><div>To assess population-level changes in VKA treatment quality and incidence of clinical events, including bleeding and venous and arterial thromboembolism, during Ramadan in the Netherlands.</div></div><div><h3>Methods</h3><div>Data from 17 Dutch anticoagulation clinics were linked to Statistics Netherlands. Prevalent VKA users in 2013-2019 with an immigration background who were likely to fast during Ramadan (ie, the Ramadan cohort) were studied from 2 months preceding Ramadan until 2 months after. During each 30-day interval, VKA treatment quality and risk of clinical events were assessed. A cohort of native Dutch VKA users was studied as negative control.</div></div><div><h3>Results</h3><div>The Ramadan cohort included 3835 VKA users (median age 65.8 years, 55.2% male). Frequency of international normalized ratio (INR) monitoring, INR variability, and time within target range remained similar across Ramadan. However, the proportion of supratherapeutic INRs was slightly higher during (18.9% ± 31.5% [mean ± SD]) and after Ramadan (month +1, 19.9% ± 32.7% and month +2, 19.7% ± 32.8%) compared with before (month –2, 18.1 ± 30.9% and month –1, 17.8 ± 31.5%). Meanwhile, there was a higher proportion of clinically relevant dose reductions during Ramadan (4.7%) than the other months (3.6%-4.3%). These were not observed in the native Dutch cohort (<em>N</em> = 139,207). Monthly risk of the composite of bleeding and thromboembolic events remained unchanged across Ramadan in both cohorts.</div></div><div><h3>Conclusion</h3><div>There were no clinically relevant population-level changes across Ramadan in VKA treatment quality and clinical outcomes, except for a slightly higher proportion of supratherapeutic INRs and dose reductions.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 103010"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired von Willebrand syndrome in children","authors":"Emmanuel J. Favaloro ,&nbsp;Leonardo Pasalic","doi":"10.1016/j.rpth.2025.103169","DOIUrl":"10.1016/j.rpth.2025.103169","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 103169"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative targeted proteomics for occult cancer screening in patients with unprovoked venous thromboembolism: results from the prospective PLATO-VTE study","authors":"Noori A.M. Guman ,&nbsp;Noémie Kraaijpoel ,&nbsp;Frits I. Mulder ,&nbsp;Marc Carrier ,&nbsp;Luis Jara-Palomares ,&nbsp;Marcello Di Nisio ,&nbsp;Walter Ageno ,&nbsp;Jan Beyer-Westendorf ,&nbsp;Frederikus A. Klok ,&nbsp;Thomas Vanassche ,&nbsp;Johannes M.M.B. Otten ,&nbsp;Benilde Cosmi ,&nbsp;Mike J.L. Peters ,&nbsp;Marije ten Wolde ,&nbsp;Aurélien Delluc ,&nbsp;Pieter W. Kamphuisen ,&nbsp;Verónica Sánchez-López ,&nbsp;Ettore Porreca ,&nbsp;Jip Ramaker ,&nbsp;Patrick M.M. Bossuyt ,&nbsp;Yassene Mohammed","doi":"10.1016/j.rpth.2025.103018","DOIUrl":"10.1016/j.rpth.2025.103018","url":null,"abstract":"<div><h3>Background</h3><div>About 5% of patients with unprovoked venous thromboembolism (VTE) have occult cancer. Despite standard cancer screening, 50% of cancers remain undetected.</div></div><div><h3>Objectives</h3><div>We used quantitative targeted proteomics to identify novel cancer biomarkers among patients with unprovoked VTE.</div></div><div><h3>Methods</h3><div>Patients aged ≥40 years with a first unprovoked VTE and without a malignancy in the preceding 5 years were invited to an international prospective cohort study. Plasma samples were collected within 10 days after VTE. The primary outcome was an adjudicated cancer diagnosis during 12-month follow-up. Concentrations of 269 plasma proteins covering coagulation, complement, and cancer-associated pathways were measured using quantitative mass spectrometry-based targeted proteomics. In a nested case-control study, protein profiles of patients with cancer were compared with those of randomly sampled unique control patients (ratio 3:1). Proteins with an unadjusted <em>P</em> value &lt; .05 and fold change ≥15% were combined in a multivariable logistic regression model. To address the variability in the obtained model, the protein selection and model-building approach were replicated in 250 bootstrap samples, and an optimism-adjusted c-statistic was calculated.</div></div><div><h3>Results</h3><div>Of the 476 included participants, 28 (5.9%) were newly diagnosed with cancer. Plasma samples were available for 24 cases, which were compared with those of 75 control patients. Concentrations of P-selectin, β-2 microglobulin, complement component 7, intracellular adhesion molecule 1, and lumican were higher in cases than in controls, whereas coagulation factor (F)VII, FX, and FXII, β-Ala-His dipeptidase, and kalistatin were lower. The optimism-adjusted c-statistic of the multivariable logistic regression model including these proteins was 0.78 (95% CI, 0.70-0.87).</div></div><div><h3>Conclusion</h3><div>Ten differentially abundant proteins were identified in patients with occult cancer, suggesting potential of plasma proteomic tests as novel biomarker for occult cancer in patients with unprovoked VTE.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 6","pages":"Article 103018"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}