Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Tissue factor detection in mouse tissues by western blotting using commercial antibodies","authors":"Megan V. Perkins ,&nbsp;Sierra J. Archibald ,&nbsp;Ana T.A. Sachetto ,&nbsp;Nigel Mackman","doi":"10.1016/j.rpth.2025.103336","DOIUrl":"10.1016/j.rpth.2025.103336","url":null,"abstract":"<div><h3>Background</h3><div>Tissue factor (TF) is a receptor for factor (F)VII/FVIIa and is essential for hemostasis. TF is expressed in a tissue-specific manner, with differing TF levels across tissues. TF expression is increased in a variety of diseases, so accurate measurement of TF protein levels is important.</div></div><div><h3>Objectives</h3><div>The goal of this study was to evaluate the ability of 4 commercial antibodies to measure TF in various mouse tissues using western blotting.</div></div><div><h3>Methods</h3><div>We used the goat anti-mouse TF polyclonal antibody AF3178 (R&amp;D Systems), the rabbit anti-mouse TF monoclonal antibody ab189483 (Abcam), the rabbit anti-mouse TF monoclonal antibody 44861 (Cell Signaling Technology), and the mouse anti-mouse TF monoclonal antibody H9 (Santa Cruz Biotechnology) to measure TF in the mouse pancreatic cancer cell line KPC2 wild-type and KPC2 TF knockout cell lysates, as well as various tissues from wild-type and low TF mice (no mouse TF expression) using western blotting.</div></div><div><h3>Results</h3><div>All 4 antibodies detected TF in KPC2 wild-type cells but not in KPC2 TF knockout cells. All 4 antibodies detected TF in the brain, lung, heart, kidney, and spleen. The relative amounts of TF in these tissues were consistent with the tissue distribution of TF mRNA reported in previous studies. Nonspecific bands were detected in various tissues with the different antibodies.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that the Abcam and Cell Signaling Technology anti-mouse TF monoclonal antibodies gave the strongest signal for TF in mouse tissues. However, researchers should be aware that all 4 antibodies also detect nonspecific bands in some tissues.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103336"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022851","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":"PAR for the course – protease-activated receptor 4 protects the brain from hemorrhage","authors":"Izabella Andrianova ,&nbsp;Frederik Denorme","doi":"10.1016/j.rpth.2025.103337","DOIUrl":"10.1016/j.rpth.2025.103337","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103337"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022847","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":"Venous thromboembolism and 20-year cancer risk: a Danish population-based cohort study","authors":"Søren K. Martiny ,&nbsp;Vincent Lanting ,&nbsp;Dóra K. Farkas ,&nbsp;Nick van Es ,&nbsp;Henrik T. Sørensen","doi":"10.1016/j.rpth.2025.103318","DOIUrl":"10.1016/j.rpth.2025.103318","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is associated with an elevated short-term cancer risk, but data on the long-term risk are conflicting. The mechanisms linking patients with VTE to elevated long-term cancer risk remain largely unknown.</div></div><div><h3>Objectives</h3><div>To investigate long-term cancer risk after VTE and whether this risk pertained predominantly to cancers sharing risk factors with VTE.</div></div><div><h3>Methods</h3><div>Using nationwide Danish registries, we followed patients with first-time VTE (1996-2022) until cancer diagnosis, death, emigration, or December 31, 2022, whichever occurred first. We used the Aalen–Johansen estimator to compute cumulative cancer incidence, treating death as a competing event. Standardized incidence ratios (SIRs) compared observed events with expected events based on general population rates. We analyzed cancer incidence overall and by site-specific and etiology groups for smoking-, obesity-, alcohol-, hormone-, and infection-related cancers, and “all other” cancers.</div></div><div><h3>Results</h3><div>We followed 138,049 patients for a median of 5.5 years. The 1-year cancer risk was 4.0%. The 1-year SIR was 3.45 (95% CI, 3.36-3.55), then ranged from 1.09 to 1.16 over 20 years of follow-up, reaching 1.00 (95% CI, 0.90-1.11) thereafter. SIR was elevated in all cancer groups within 1 year and afterward, but was driven by site-specific cancers often related to smoking, obesity, and alcohol (lung, pharynx, larynx, esophagus, stomach, liver, pancreas, and colon), as well as hematological cancers.</div></div><div><h3>Conclusion</h3><div>Compared with the general population, patients with VTE had an increased cancer risk for up to 20 years. Shared risk factors, such as lifestyle-related factors and genetic predisposition, may contribute to this increased risk.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103318"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078267","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":"Comparison of changes in blood cells and hemostatic biomarkers in mouse xenograft models of acute myeloid leukemia and acute promyelocytic leukemia","authors":"Sierra J. Archibald ,&nbsp;Ana T.A. Sachetto ,&nbsp;Xingru Zhu ,&nbsp;Radhika Gangaraju ,&nbsp;Nigel Mackman ,&nbsp;Yohei Hisada","doi":"10.1016/j.rpth.2025.103319","DOIUrl":"10.1016/j.rpth.2025.103319","url":null,"abstract":"<div><h3>Background</h3><div>Leukemia patients have an increased risk of both thrombosis and bleeding due to a dysregulated hemostatic system. Levels of coagulation and fibrinolysis activation markers are increased, whereas levels of platelets and fibrinogen are decreased in leukemia patients. Mouse models can be used to study the pathways that contribute to coagulopathy in leukemia.</div></div><div><h3>Objectives</h3><div>To measure blood cells and hemostatic biomarkers in a mouse xenograft model of acute myeloid leukemia (AML) and compare them with a mouse xenograft model of acute promyelocytic leukemia (APL).</div></div><div><h3>Methods</h3><div>We established a mouse xenograft model of AML by injecting HL-60-Luc2 cells into NOD.Cg-<em>Prkdc</em>^{<em>scid</em>} <em>Il2rg</em>^{<em>tm1Wjl</em>}/SzJ mice and monitored the growth of leukemic cells by measuring luciferase expression. Levels of blood cells and hemostatic biomarkers were measured in leukemic mice. The parameters of the AML model were compared with those of the APL model using NB4-Luc cells.</div></div><div><h3>Results</h3><div>AML mice exhibited an increase in white blood cells, an increase in a marker of coagulation activation (thrombin-antithrombin complexes), an increase in a marker of fibrinolysis activation (plasmin-antiplasmin complexes), and a decrease in platelets and fibrinogen compared with control mice. No increase in white blood cell counts was observed in APL mice. APL mice had significantly higher levels of thrombin-antithrombin complexes compared with AML mice.</div></div><div><h3>Conclusion</h3><div>These leukemia mouse models can be used to understand how the hemostatic system is dysregulated in leukemia.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103319"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978123","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":"Factor VII deficiency is more prevalent than previously reported","authors":"Lukas Löwing Svensson ,&nbsp;Elisabeth Aardal ,&nbsp;Margareta Holmström","doi":"10.1016/j.rpth.2025.103284","DOIUrl":"10.1016/j.rpth.2025.103284","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of factor (F)VII deficiency is estimated at approximately 1 of 500,000 individuals. However, low FVII activity (FVII:C) is frequently observed in a population of &lt;500,000 in the region of Östergötland, Sweden.</div></div><div><h3>Objectives</h3><div>To estimate the prevalence and bleeding tendency of adult FVII-deficient patients in Östergötland, Sweden.</div></div><div><h3>Methods</h3><div>In this retrospective cross-sectional study, the laboratory information system was used to identify adult patients with at least one FVII:C result ≤ 0.50 kilo International Units per Liter (kIU/L) between January 1, 2017, and December 31, 2022. The most likely cause was established, and in patients with a FVII deficiency, as defined by the Nordic Hemophilia Council (FVII:C &lt; 0.35 kIU/L) or low FVII level (0.35-0.50 kIU/L), the bleeding tendency was evaluated.</div></div><div><h3>Results</h3><div>FVII:C ≤ 0.50 kIU/L was identified in 97 patients residing in Östergötland. Of these, 21 had FVII deficiency, and 39 had low FVII level, corresponding to a prevalence of at least 1 of 17,800 and 1 of 9600 in the adult population in Östergötland, respectively. Patients with FVII deficiency differed significantly from patients with low FVII level in bleeding symptoms (<em>P</em> = .01). Of the FVII-deficient patients, 38% were asymptomatic, while 19% and 24% had experienced minor and major spontaneous bleedings, respectively.</div></div><div><h3>Conclusion</h3><div>The prevalence of FVII deficiency was estimated to be at least 1 of 17,800 adults, which is 28 times higher than the internationally claimed prevalence. Spontaneous bleeding occurred in 43% of these individuals.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103284"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885068","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":"Joint tissue plasticity in hemophilia: insights from the Joint Activity and Damage Exam ultrasound protocol","authors":"Parthiv Sheth ,&nbsp;Khang Tong ,&nbsp;Bilgimol Chumappumkal Joseph ,&nbsp;Tina Manon-Jensen ,&nbsp;Michael Glenzer ,&nbsp;Isaac Nwi-Mozu ,&nbsp;Peter Aguero ,&nbsp;Bruno Steiner ,&nbsp;Cindy Bailey ,&nbsp;Doris V. Quon ,&nbsp;Rebecca Kruse-Jarres ,&nbsp;Euyhyun Lee ,&nbsp;Morten Asser Karsdal ,&nbsp;Lin Liu ,&nbsp;Annette von Drygalski","doi":"10.1016/j.rpth.2025.103290","DOIUrl":"10.1016/j.rpth.2025.103290","url":null,"abstract":"<div><h3>Background</h3><div>Progressive arthropathy is a debilitating condition that affects hemophilic joints as a consequence of hemarthroses. However, our understanding of the trajectory of potentially destructive processes at the tissue level remains limited and requires longitudinal imaging studies.</div></div><div><h3>Objectives</h3><div>To longitudinally characterize ultrasonographic joint tissue changes in adults with hemophilia using the Joint Activity and Damage Exam (JADE) protocol, and to examine their relationships with joint health status, hemarthrosis, and serum biomarkers of tissue turnover.</div></div><div><h3>Methods</h3><div>We prospectively studied adults with hemophilia (A or B) of any severity and associated arthropathy at 3 North American sites. We assessed joint health using the Hemophilia Joint Health Score (HJHS) and musculoskeletal ultrasound, as well as the Joint Activity and Damage Exam protocol for direct measurements of osteochondral alterations, cartilage, and soft tissue in the elbows, ankles, and knees at study entry and at ∼12 to 18 and ∼24 to 36 months thereafter. Reported hemarthrosis between study visits was verified by musculoskeletal ultrasound. We analyzed tissue rate changes in healthy (HJHS 0-3) and unhealthy (HJHS ≥ 4) joints, as well as in joints with and without hemarthrosis. Associations between tissue measurements and serially obtained serum biomarkers (C4M, PRO-C4, and C3M) were explored using logistic regression.</div></div><div><h3>Results</h3><div>The median age (<em>N</em> = 44) was 36.5 years. Joints (133 healthy and 131 unhealthy at baseline) were evaluated serially. Only 16 joints experienced at least 1 hemarthrosis. At baseline, unhealthy joints had significantly thinner cartilage and increased osteochondral alterations and soft tissue swelling (all <em>P</em> values &lt; .001). While individual joint tissues followed either a positive or negative trajectory of expansion or contraction over the ensuing 2 to 3 years, mean rate changes were not significantly different between healthy and unhealthy joints. Hemarthrosis resulted in a predilection for cartilage thinning and positive rate changes in PRO-C4 (<em>P</em> = .006).</div></div><div><h3>Conclusion</h3><div>Ultrasonographic tissue measurements discriminated between healthy and unhealthy joints at baseline. Measurements revealed a dynamic pattern of tissue plasticity not only in healthy but also in unhealthy and bleeding joints, suggesting potential for reversibility of often-assumed irreversible intra-articular damage in hemophilic joints.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103290"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885113","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":"Predicting venous thromboembolism risk from endogenous thrombin potential-based normalized activated protein C sensitivity ratio assay: toward early assessment of combined oral contraceptives","authors":"Laure Morimont ,&nbsp;Mitchell D. Creinin ,&nbsp;Ulysse Gaspard ,&nbsp;Jean-Michel Foidart ,&nbsp;Jonathan Douxfils","doi":"10.1016/j.rpth.2025.103285","DOIUrl":"10.1016/j.rpth.2025.103285","url":null,"abstract":"<div><h3>Background</h3><div>Combined oral contraceptives (COCs) increase venous thromboembolism (VTE) risk, depending on estrogen type, dose, and progestin. While epidemiological studies provide insight into these risks, they require years to complete. The normalized activated protein C sensitivity ratio (nAPCsr), a standardized assay of acquired activated protein C resistance, has emerged as a potential biomarker of COC-induced VTE risk.</div></div><div><h3>Objectives</h3><div>To develop a population-based <em>in silico</em> model predicting VTE risk associated with various COC formulations based on their mean nAPCsr values.</div></div><div><h3>Methods</h3><div>We analyzed 200 plasma samples from non-COC users and 257 from users of 9 different COCs. We constructed an exponential model to correlate the mean nAPCsr of 5 COCs with their available population-based VTE relative risk, as extracted from <em>a published</em> meta-analysis. We assessed model performance using <em>R</em>², Spearman’s rank correlation coefficient, and the root mean square error, and performed a sensitivity analysis by excluding COC nonusers. We then estimated population-based VTE risks for the 4 COCs not used in model construction.</div></div><div><h3>Results</h3><div>The model demonstrated high predictive accuracy (R² = .96; root mean square error = 0.21; Spearman correlation coefficient = 1) and remained robust despite group size imbalance. Predicted VTE risks for ethinylestradiol 30 μg with dienogest 2 mg, ethinylestradiol 20 μg with drospirenone 3 mg, estradiol 1.5 mg with nomegestrol acetate 2.5 mg, and estetrol 15 mg with drospirenone 3 mg were 4.36, 3.43, 1.50, and 1.45, respectively, consistent with or complementary to existing epidemiological evidence.</div></div><div><h3>Conclusion</h3><div>Our model, based on mean nAPCsr, provides a reliable, biomarker-based approach for predicting population-based COC-related VTE risk. This strategy could help shorten the time between product launch and population-based risk assessment.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103285"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978124","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":"Response to: “DOACs for Left Ventricular Thrombus: Persistent Equipoise Despite New Observational and Randomized Data”","authors":"Hossam Elbenawi ,&nbsp;Kirsten Lipps ,&nbsp;Samuel Heller Jr. ,&nbsp;David A. Liedl ,&nbsp;Raymond C. Shields ,&nbsp;Ana I. Casanegra ,&nbsp;Stanislav Henkin ,&nbsp;Thom W. Rooke ,&nbsp;Paul W. Wennberg ,&nbsp;Waldemar E. Wysokinski ,&nbsp;Robert D. McBane ,&nbsp;Damon E. Houghton","doi":"10.1016/j.rpth.2025.103340","DOIUrl":"10.1016/j.rpth.2025.103340","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103340"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078268","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":"Comparing survival with vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants in patients with cancer—a systematic review and meta-analysis","authors":"Vasiliki Xirou ,&nbsp;Anika Patel ,&nbsp;Maria Fernanda Albuja Altamirano ,&nbsp;Rishabh Singh ,&nbsp;Jason Gusdorf ,&nbsp;Kevin Barnum ,&nbsp;Megan McNichol ,&nbsp;Justine Ryu ,&nbsp;Jeffrey I. Zwicker ,&nbsp;Thita Chiasakul ,&nbsp;Rushad Patell","doi":"10.1016/j.rpth.2025.103268","DOIUrl":"10.1016/j.rpth.2025.103268","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is a frequent complication in malignancy. Low-molecular-weight heparins and direct oral anticoagulants have replaced vitamin K antagonists (VKAs) as the standard of care for cancer-associated VTE. Nonetheless, clinical trials have not established a survival benefit of these agents compared with VKA.</div></div><div><h3>Objectives</h3><div>We conducted a systematic review and meta-analysis to compare survival in cancer patients receiving VKA vs other anticoagulants.</div></div><div><h3>Methods</h3><div>We searched Embase, Web of Science, PubMed, <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, and Cochrane from inception until April 10, 2025, focusing on the use of VKA and non-VKA in cancer patients. Primary outcome was mortality and secondary outcomes included thromboembolism and bleeding.</div></div><div><h3>Results</h3><div>Of 11,198 studies screened, 14 studies (70,025 patients) were included. VKA were associated with lower mortality than non-VKA in observational studies (odds ratio [OR], 0.84; 95% CI, 0.78-0.91; <em>I</em>² = 81%; <em>n</em> = 6 studies) but not in randomized controlled trials (OR, 0.99; 95% CI, 0.86-1.13; <em>I</em>² = 0%; <em>n</em> = 8 studies). In subgroup analysis, follow-up period of &gt;6 months (OR, 0.85; 95% CI, 0.79-0.92; <em>I</em>² = 75%), solid malignancies (OR, 0.81; 95% CI, 0.75-0.88; <em>I</em>² = 78%), and indication of VTE only (OR, 0.89; 95% CI, 0.83-0.96; <em>I</em>² = 42%) demonstrated improved survival with VKA.</div></div><div><h3>Conclusion</h3><div>The use of VKA was associated with lower mortality than non-VKA anticoagulation in patients with cancer in observational studies but not in randomized trials. The analysis was limited by high heterogeneity, which must be considered when interpreting results.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103268"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927162","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":"Monitoring ADAMTS-13 conformation in immune-mediated thrombotic thrombocytopenic purpura: toward personalized management","authors":"Bérangère S. Joly ,&nbsp;Elien Roose ,&nbsp;Charlotte Dekimpe ,&nbsp;Karen Vanhoorelbeke ,&nbsp;Agnès Veyradier ,&nbsp;Paul Coppo","doi":"10.1016/j.rpth.2025.103288","DOIUrl":"10.1016/j.rpth.2025.103288","url":null,"abstract":"<div><h3>Background</h3><div>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy caused by an autoimmune-driven deficiency of ADAMTS-13. Despite remission, relapses remain a major concern for patients and are currently predicted by monitoring ADAMTS-13 activity.</div></div><div><h3>Objectives</h3><div>This study evaluated the association between ADAMTS-13 conformation and relapse risk in patients with iTTP during follow-up.</div></div><div><h3>Methods</h3><div>We conducted a retrospective monocentric study involving patients with iTTP with ADAMTS-13 monitoring from 2008 to 2020. ADAMTS-13 antigen and conformation were assessed in plasma samples using our 3H9-ELISA and 1C4-ELISA, respectively.</div></div><div><h3>Results</h3><div>Fifteen patients with iTTP were monitored for a median of 7 years (IQR, 6-11) with a total of 479 plasma samples. Based on annual relapse rate (RR; median, 0.5), they were categorized as low (group 1; RR, &lt;0.50, <em>n</em> = 8) or high relapsers (group 2; RR, ≥0.50, <em>n</em> = 7). ADAMTS-13 activity normalized between iTTP relapses in all patients. However, the time from normalization with an open conformation to relapse was shorter in group 2 (5 vs 21 months; <em>P</em> &lt; .001). Median annual ADAMTS-13 activity differ significantly between groups (54.1% vs 50.0%; <em>P</em> = .1893). A trend suggested greater time spent in an open conformation in group 2 (0.6 vs 0.2; <em>P</em> = .1427). Rituximab was effective in group 1, while group 2 patients often required alternative therapies.</div></div><div><h3>Conclusion</h3><div>Persistent open ADAMTS-13 conformation in remission samples was observed more frequently in patients with higher relapse risk and could potentially serve as a biomarker for detecting low levels of circulating autoantibodies. This potential biomarker requires prospective validation before it can be used to guide individualized iTTP management.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103288"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927164","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}