Journal of Thrombosis and Haemostasis最新文献

{"title":"A critical role for MALAT1 in gram-negative bacteria-induced coagulation via regulation of caspase-11 signaling","authors":"Chuang Yuan ,&nbsp;Jizhen Cai ,&nbsp;Fangfang Yuan ,&nbsp;Hongli Li ,&nbsp;Cheng Cheng ,&nbsp;Yueqing Cao ,&nbsp;Rui Tan ,&nbsp;Xue Mi ,&nbsp;Tingxuan Hu ,&nbsp;Can Li ,&nbsp;Minyi Zhao ,&nbsp;Mikael C.I. Karlsson ,&nbsp;Jianfeng Wu ,&nbsp;Jing Zhang ,&nbsp;Xinyu Yang","doi":"10.1016/j.jtha.2025.10.037","DOIUrl":"10.1016/j.jtha.2025.10.037","url":null,"abstract":"<div><h3>Background</h3><div>Our previous animal studies suggested the critical role of the type I interferon (IFNβ) and high-mobility group box 1 (HMGB1) axis in coagulation; however, the predictive value of IFNβ/HMGB1 for the clinical onset of septic disseminated intravascular coagulation (DIC) remains unknown.</div></div><div><h3>Objectives</h3><div>This study aimed to further elaborate on the pathogenesis of sepsis-associated DIC and identify potential biomarkers suitable for the early prediction of DIC.</div></div><div><h3>Methods</h3><div>IFNβ/HMGB1 plasma levels were measured in septic patients without DIC at admission. The onset of septic DIC was assessed 48 hours thereafter. We subsequently compared the leukocyte transcriptomes of patients with and without DIC. A series of genetically modified mice, including <em>IFNα/βR1</em>^{<em>−/−</em>}<em>, Tlr4</em>^{<em>−/−</em>}<em>, Malat1</em>^{<em>−/−</em>}, <em>Casp1</em>^{<em>−/−</em>}, and <em>Casp11</em>^{<em>−/−</em>} mice, as well as <em>Malat1</em>^{<em>flox/flox</em>} or <em>Gpx4</em>^{<em>flox/flox</em>} in combination with <em>Cdh5</em>-, <em>Alb</em>-, <em>Vav</em>- and <em>Lyz2</em>-Cre mice, were used to investigate the mechanisms.</div></div><div><h3>Results</h3><div>The plasma level of IFNβ but not HMGB1 in septic patients showed a consistent correlation with the onset of DIC. We identified an HMGB1-bypassing signaling pathway in which IFNβ stimulates macrophages to express high levels of the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in response to gram-negative bacteria. Deletion of <em>Malat1</em> specifically in macrophages restored glutathione exhaustion and enhanced glutathione peroxidase 4 activity by maintaining Yin-Yang 1-mediated Hba-a1 expression, which dampens lipopolysaccharide internalization and caspase-11 activation, and suppressed caspase-11/GSDMD-dependent phosphatidylserine exposure, thereby protecting against bacteria-induced coagulation.</div></div><div><h3>Conclusion</h3><div>Our study unveils a novel immunocoagulation pathway in which MALAT1 fuels caspase-11-dependent coagulation by inhibiting glutathione peroxidase 4 activity, which provides new insights into the coagulation mechanisms in bacterial sepsis.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 1014-1031"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of acute pulmonary embolism: a comparison of international guideline recommendations","authors":"Casper Falster ,&nbsp;Gro Egholm ,&nbsp;Jess Lambrechtsen ,&nbsp;Asger Andersen ,&nbsp;Thomas Agerbo Gaist ,&nbsp;Rupert Bauersach ,&nbsp;Frederikus A. Klok ,&nbsp;Anton Vonk-Noordegraaf","doi":"10.1016/j.jtha.2025.11.021","DOIUrl":"10.1016/j.jtha.2025.11.021","url":null,"abstract":"<div><div>Pulmonary embolism is a common cardiovascular cause of death. Following diagnosis, immediate risk stratification and initiation of treatment are crucial but challenging, as patients may rapidly deteriorate in cases of progressive right heart failure. Multiple approaches to standardized risk stratification and subsequent management have been proposed, including assessment of clinical parameters such as cardiac biomarkers and imaging evidence of right ventricular abnormalities; however, obtaining an overview of the strengths and weaknesses of the multiple proposed approaches to risk stratification and subsequent management might be overwhelming for physicians not routinely involved in the treatment of acute pulmonary embolism. Fourteen international guidelines have been authored by medical societies or expert author groups over the past 20 years, offering recommendations on aspects of the management of pulmonary embolism, some of which are characterized by notable heterogeneity. This review summarizes and compares the main recommendations of each guideline, considers the most recent evidence for each topic, and provides a synthesis of the most common recommendations.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 817-836"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticoagulation Reversal and the Risk of Arterial Thrombosis - A Double-Edged Sword","authors":"Joseph R. Shaw","doi":"10.1016/j.jtha.2025.12.003","DOIUrl":"10.1016/j.jtha.2025.12.003","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 863-865"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survey on current practice in thrombophilia testing: from phenotype to genotype. Communication from the SSC of the ISTH","authors":"Christine Van Laer ,&nbsp;Gary W. Moore ,&nbsp;Rinku Majumder ,&nbsp;Javier Corral ,&nbsp;Kathleen Freson ,&nbsp;Vera Ignjatovic ,&nbsp;Christelle Orlando","doi":"10.1016/j.jtha.2025.10.032","DOIUrl":"10.1016/j.jtha.2025.10.032","url":null,"abstract":"<div><div>Diagnosing inherited thrombophilia as the cause of venous thromboembolism is important for patient management. Deficiencies in antithrombin, protein C, and protein S are usually diagnosed by plasma-based assays. Genetic testing can confirm the congenital nature of these deficiencies. Factor V Leiden can be detected using activated protein C resistance assays, followed by or replaced by molecular confirmation, whereas prothrombin G20210A can only be detected genetically. During the last decade, molecular techniques have evolved from single-gene sequencing to multigene sequencing panels. To understand current thrombophilia testing practices, a questionnaire was designed focusing on thrombophilia testing in coagulation laboratories and how genetic testing is placed in the diagnostic workflow. All International Society on Thrombosis and Haemostasis members and participants in external quality control schemes on thrombophilia testing were invited to complete the survey. Eighty-two unique responses were received. This international survey showed that laboratories perform plasma-based thrombophilia testing, but 42% restrict it to requests from thrombosis/hemostasis specialists, patients without anticoagulant treatment, or those with a strong personal of familial history of venous thrombosis. However, phenotypic testing is not always performed according to published guidelines. More specifically, the transference of reference intervals from manufacturers or literature is often suboptimal. For results interpretation, anticoagulant use and acquired causes were considered the most. Genetic testing is not systematically included in the diagnostic work-up algorithms and is mostly restricted to single-variant testing. Multigene panel testing is only performed by a minority of laboratories. Our results highlight the necessity for recommendations on how and when to perform this kind of testing.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 1171-1180"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A UK-wide analysis of 2265 patients receiving a reversal agent for direct oral anticoagulant–associated bleeding","authors":"","doi":"10.1016/j.jtha.2025.11.003","DOIUrl":"10.1016/j.jtha.2025.11.003","url":null,"abstract":"<div><h3>Background</h3><div>Reversal agents are used in patients taking direct oral anticoagulants (DOACs) to manage bleeding, but evidence for their effectiveness remains limited.</div></div><div><h3>Objectives</h3><div>This study assessed the proportion of patients treated with a reversal agent for DOAC-associated bleeding who had major bleeding and evaluated their outcomes.</div></div><div><h3>Methods</h3><div>This was a retrospective, observational audit across 65 hospitals in the United Kingdom. Adults who received andexanet alfa, idarucizumab, or 4-factor prothrombin complex concentrate (4F-PCC) for DOAC-associated bleeding between October 2020 and June 2023 were included. Data were collected on demographics, medical history, bleed site and severity, reversal agent, thrombosis, and 90-day mortality. A propensity score–matched analysis was performed to estimate the cumulative incidence of thrombosis and death according to reversal agent in gastrointestinal hemorrhage.</div></div><div><h3>Results</h3><div>Of 2265 patients, 875 (38.6%) had gastrointestinal bleeding and 1012 (44.7%) had intracranial hemorrhage. Median age was 81 years. Median time from bleed onset to reversal was 6.5 hours, and that from last anticoagulant dose was 16.0 hours. Of 1253 patients with nonintracranial bleeds, 1001 (79.9%) had major hemorrhage. In a propensity score–matched analysis of 494 patients with gastrointestinal bleeding, there was no significant difference in 90-day-mortality with andexanet alfa compared with that with 4F-PCC (36.4% vs 32.4%), but andexanet alfa was associated with a significantly increased 30-day incidence of stroke (4.5% vs 0%).</div></div><div><h3>Conclusion</h3><div>Reversal agents were generally used in patients with clinical evidence of major bleeding but were administered long after the last anticoagulant dose. In gastrointestinal bleeding, andexanet alfa was associated with a higher thrombotic risk than 4F-PCC.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 900-912"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombotic thrombocytopenic purpura following allogeneic hematopoietic stem cell transplantation: a rare but fatal complication","authors":"Zhixue Li ,&nbsp;Peng Zhao ,&nbsp;Haixia Fu ,&nbsp;Chencong Wang ,&nbsp;Yun He ,&nbsp;Xiaolu Zhu ,&nbsp;Qiusha Huang ,&nbsp;Jin Wu ,&nbsp;Yuanyuan Zhang ,&nbsp;Fengrong Wang ,&nbsp;Wei Han ,&nbsp;Chenhua Yan ,&nbsp;Zhidong Wang ,&nbsp;Jun Kong ,&nbsp;Tingting Han ,&nbsp;Jingzhi Wang ,&nbsp;Yao Chen ,&nbsp;Meng Lv ,&nbsp;Yuqian Sun ,&nbsp;Yuhong Chen ,&nbsp;Xiaohui Zhang","doi":"10.1016/j.jtha.2025.11.015","DOIUrl":"10.1016/j.jtha.2025.11.015","url":null,"abstract":"<div><h3>Background</h3><div>Thrombotic microangiopathy (TMA) is a common and potentially fatal complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thrombotic thrombocytopenic purpura (TTP), a distinct form of TMA caused by severe deficiency of plasma ADAMTS-13 activity, has been reported to be rare in the posttransplant population.</div></div><div><h3>Objectives</h3><div>To investigate the clinical features and outcomes of TTP after allo-HSCT.</div></div><div><h3>Methods</h3><div>This retrospective cohort study used a nested case‒control approach. For each patient with TTP, 3 patients with high-risk transplant-associated TMA (TA-TMA) were matched as controls according to the time of transplantation.</div></div><div><h3>Results</h3><div>A total of 26 patients with TTP were identified and included in the cohort. Compared with patients with high-risk TA-TMA, patients with TTP had greater proportions of central nervous system (50.0% vs 19.2%, <em>P</em> = .002) and gastrointestinal tract involvement (65.4% vs 32.1%, <em>P</em> = .003), with central nervous system dysfunction occurring later (8.0 days vs −1.0 days since the diagnosis of TTP, <em>P =</em> .008). Patients with TTP had a significantly lower overall survival rate than those with high-risk TA-TMA (26.9% vs 48.7%, log-rank <em>P =</em> .026). Age &gt;40 years at the time of TTP diagnosis was identified as an independent predictor of 60-day overall survival.</div></div><div><h3>Conclusion</h3><div>TTP occurring in the setting of HSCT is rare but can be differentiated from TA-TMA and is associated with a worse prognosis.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 1067-1078"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1 gain of function induces a platelet preactivation state","authors":"Christilla Bachelot-Loza ,&nbsp;Aurore Marchelli ,&nbsp;Laurie Ruch ,&nbsp;Divina El Hamaoui ,&nbsp;Julien Demagny ,&nbsp;Bruna Salau Grau ,&nbsp;Clarisse Mouriaux ,&nbsp;Wafa Amara ,&nbsp;Anaïs Mehl ,&nbsp;Emma Ziessel ,&nbsp;Shaymaa Alhabib ,&nbsp;My Ngoc Ha ,&nbsp;Fatima Zemali ,&nbsp;Sophie Gandrille ,&nbsp;Véronique Picard ,&nbsp;Pierre Mangin ,&nbsp;Régis Bobe ,&nbsp;Loïc Garçon ,&nbsp;Catherine Léon ,&nbsp;Pascale Gaussem","doi":"10.1016/j.jtha.2025.11.028","DOIUrl":"10.1016/j.jtha.2025.11.028","url":null,"abstract":"<div><h3>Background</h3><div>Hereditary xerocytosis (HX) is a dominant red blood cell membrane disorder characterized by dehydration and hemolysis. Most HX cases result from gain-of-function (GOF) mutations in the <em>PIEZO1</em> gene, which encodes a mechanosensitive ion channel permeable to calcium when activated. Evolution of HX is characterized by frequent thromboembolic events after splenectomy.</div></div><div><h3>Objectives</h3><div>Given the major role of calcium during platelet activation, we hypothesized that Piezo1 GOF may increase platelet activation and contribute to thrombosis.</div></div><div><h3>Methods</h3><div>Human washed platelets were activated by various agonists in the presence of Yoda1 (a chemical Piezo1 activator). Aggregation was monitored in an aggregometer, secretion by flow cytometry and calpain activation by western blot. Mouse models were the R2482H knock-in, mimicking the human recurrent R2456H GOF mutation of PIEZO1, and the megakaryocyte lineage-specific Piezo1/2 knockout (KO). <em>Ex vivo</em> thrombus formation was performed under flow on a collagen surface. <em>In vivo</em>, tail bleeding time was measured.</div></div><div><h3>Results</h3><div>Yoda1 alone had no effect on human platelets but potentiated agonist-induced platelet aggregation, secretion, and procoagulant activity, involving calpain activation. In <em>ex vivo</em>, GOF mouse platelets aggregated more than wild type, especially in flow conditions. Conversely, blood from KO mice formed smaller thrombi. <em>In vivo</em>, a shorter total tail bleeding time was found in Piezo1 GOF mice, while KO mice had a longer first bleeding time.</div></div><div><h3>Conclusion</h3><div>These results therefore support a correlation between Piezo1 activated status and platelet activation and are consistent with the involvement of platelet Piezo1 GOF in thrombotic events reported in patients with HX.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 1118-1129"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-based risk stratification of patients with acute pulmonary embolism: communication from the ISTH SSC Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease","authors":"Rosa Talerico ,&nbsp;Kerstin de Wit ,&nbsp;Stefano Barco ,&nbsp;Jose Bonorino ,&nbsp;Corstiaan den Uil ,&nbsp;Carlos Elzo Kraemer ,&nbsp;Federico Germini ,&nbsp;Aaron Iding ,&nbsp;Aubrey Jones ,&nbsp;Stavros Konstantinides ,&nbsp;Camila Masias ,&nbsp;Anna L. Parks ,&nbsp;Helia Robert-Ebadi ,&nbsp;Tobias Tritschler ,&nbsp;Maria Cristina Vedovati ,&nbsp;David R. Vinson ,&nbsp;Scott C. Woller ,&nbsp;Frederikus A. Klok","doi":"10.1016/j.jtha.2025.10.036","DOIUrl":"10.1016/j.jtha.2025.10.036","url":null,"abstract":"<div><h3>Background</h3><div>Acute pulmonary embolism (PE) includes clinical presentations with a wide spectrum of severity, making risk stratification essential to guide the decision-making process in daily practice. However, international guidelines differ in their definition of risk classes and consequent treatment recommendations.</div></div><div><h3>Objectives</h3><div>To summarize high-quality evidence supporting 4 key management decisions in acute PE: hospitalization, intensive care unit admission, reperfusion therapy, and discharge.</div></div><div><h3>Methods</h3><div>A multidisciplinary International Society on Thrombosis and Haemostasis task force, composed of international experts, conducted a literature review of randomized controlled trials and prospective management studies reporting hard clinical outcomes and assessed as having a low risk of bias, focusing on any of the 4 management decisions detailed above.</div></div><div><h3>Results</h3><div>Available evidence supports the use of either the Hestia criteria or the (simplified) PE Severity Index, combined with clinical judgment, to select PE patients for outpatient treatment. In contrast, no PE-specific evidence exists to guide intensive care unit admission. Reperfusion therapy in hemodynamically unstable patients is supported by 1 small randomized trial, while currently available high-quality evidence does not support routine reperfusion therapy in hemodynamically stable patients; therefore, hemodynamic instability remains the only established indication for reperfusion therapy to date. The decision to discharge a PE patient may be supported by the use of the (simplified) PE Severity Index, combined with clinical assessment of stability.</div></div><div><h3>Conclusion</h3><div>Overall, substantial evidence gaps persist, underscoring the need for further research to inform clinical practice and future guidelines.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 1181-1189"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is all the approved emicizumab dose essential?","authors":"Michael Makris","doi":"10.1016/j.jtha.2025.12.004","DOIUrl":"10.1016/j.jtha.2025.12.004","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"24 3","pages":"Pages 861-862"},"PeriodicalIF":5.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formation of a ternary polyphosphate-thrombin-fibrin complex attenuates thrombin activity.","authors":"Xintong Yao, James C Fredenburgh, Jeffrey I Weitz","doi":"10.1016/j.jtha.2026.01.017","DOIUrl":"10.1016/j.jtha.2026.01.017","url":null,"abstract":"<p><strong>Background: </strong>Polyphosphate (polyP) released from activated platelets acts as a procoagulant, promoting thrombin generation and fibrin formation. Like heparin, polyP binds to thrombin and fibrin(ogen).</p><p><strong>Objectives: </strong>To determine whether, like heparin, polyP promotes thrombin binding to fibrin, thereby forming a ternary polyP-thrombin-fibrin complex that modulates thrombin activity.</p><p><strong>Methods: </strong>The affinity of fluorescein isothiocyanate-labeled polyP or heparin for fibrin was determined by measuring unbound polyanion in the supernatants of fibrin clots. Likewise, the affinity of thrombin for fibrin in the absence or presence of polyanion was determined by quantifying unbound thrombin by chromogenic assay. Rate constants of thrombin inhibition by antithrombin-heparin were determined in the absence or presence of polyanion and fibrin. Clots formed with polyanions were incubated with labeled fibrinogen to monitor clot accretion.</p><p><strong>Results: </strong>PolyP and heparin bind fibrin with Kd values of 1.7 ± 0.1 μM and 1.1 ± 0.1 μM, respectively. In the presence of polyP or heparin, thrombin binds to fibrin with Kd values of 1.2 ± 0.2 μM or 0.9 ± 0.1 μM, respectively, whereas the Kd is 5.6 ± 0.4 μM in the absence of a polyanion. Thrombin within the ternary polyP-thrombin-fibrin complex is protected from inhibition by the antithrombin-heparin complex but has reduced capacity to induce fibrin accretion.</p><p><strong>Conclusions: </strong>Like heparin, polyP promotes the formation of a ternary polyP-thrombin-fibrin complex, which protects thrombin from inhibition by antithrombin-heparin. However, the ternary complex reduces the ability of clot-bound thrombin to generate fibrin. These findings highlight the interplay among polyP, thrombin, and fibrin in regulating coagulation.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}