Journal of Thrombosis and Haemostasis最新文献

{"title":"The critical role of platelet adenylyl cyclase 6 in haemostasis and thrombosis.","authors":"Beth A Webb, Lih T Cheah, Jawad S Khalil, Matthew S Hindle, Mary McKay, Neil A Turner, Mark T Kearney, Robert A S Ariens, Cedric Duval, Khalid M Naseem","doi":"10.1016/j.jtha.2025.02.045","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.02.045","url":null,"abstract":"<p><strong>Background: </strong>Platelet activation is constrained by endothelial-derived prostacyclin (PGI₂) through cyclic adenosine-5'-monophosphate (cAMP) signalling involving multiple isoforms of adenylyl cyclase (AC). The roles of specific AC isoforms in controlling haemostasis remain unclear and require clarification.</p><p><strong>Objectives: </strong>To understand the specific contribution of AC6 in platelet haemostatic and thrombotic function.</p><p><strong>Methods: </strong>A platelet-specific AC6 knockout (AC6-KO) mouse was generated. Biochemical approaches were used to determine intracellular signalling, with flow cytometry, tail bleeding time assays and in vivo thrombosis by ferric chloride were used to measure the haemostatic and thrombotic importance of platelet AC6.</p><p><strong>Results: </strong>Loss of AC6 resulted in diminished accumulation of platelet cAMP in response to PGI_2, while basal cAMP was unaffected. We found no differences in phosphodiesterase 3A (PDE3A) activity, suggesting the defect was in generation rather than hydrolysis of cAMP. Consistent with this, phosphorylation of PKA substrates, vasodilator-stimulated phosphoprotein and glycogen synthase kinase were diminished but not ablated. Functional studies demonstrated that the inhibition of thrombin-induced fibrinogen binding and P-selectin expression by PGI₂ was severely compromised, while inhibition of GPVI-mediated platelet activation was largely unaffected. Under conditions of flow formed stable thrombi, but in the absence of AC6, thrombi were insensitive to PGI₂. In vivo diminished sensitivity to PGI₂ manifested as significantly reduced tail bleeding and accelerated occlusive arterial thrombus formation in response to vascular injury that were highly unstable and prone to embolisation in AC6-KO mice.</p><p><strong>Conclusions: </strong>These data demonstrate that AC6 is linked directly to PGI₂-mediated platelet inhibition and regulation of haemostasis and thrombosis in vivo.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692666","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":"Discerning Specific Thrombolytic Activities and Blood Clot Degradomes of Diverse Snake Venoms with Untargeted Peptidomics.","authors":"Cara F Smith, Mamadou Alpha Baldé, Stephanie French, Cassandra M Modahl, Lilyrose Bahrabadi, Merilyn Amponsah-Asamoah, Keira Y Larson, Sean P Maroney, David Ceja Galindo, Martin Millimouno, Naby Camara, Jordan Benjamin, Nicklaus P Brandehoff, Maxwell C McCabe, Mitchell J Cohen, Kate Jackson, Cellou Baldé, Todd A Castoe, Stephen P Mackessy, Kirk C Hansen, Anthony J Saviola","doi":"10.1016/j.jtha.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.012","url":null,"abstract":"<p><strong>Background: </strong>Many snake venoms have been shown to possess thrombolytic activity. However, it remains unclear if actions on other clot-stabilizing proteins beyond fibrin chains contribute significantly to venom-induced thrombolysis because the clot-wide targets of venom proteases and the mechanisms responsible for thrombolysis are not well understood.</p><p><strong>Objective: </strong>Here, we utilize a high-throughput time-based thrombolysis assay in combination with untargeted peptidomics to provide comprehensive insight into the effects of venom from five snake species on blood clot degradation.</p><p><strong>Methods: </strong>We compare thrombolytic profiles across venoms with variable levels of proteases and generate venom-specific fingerprints of cleavage specificity. We also compare the specific effects of venoms that possess a range of thrombolytic activity on fibrin chains and other clot-bound proteins involved in clot structure.</p><p><strong>Results: </strong>Protease-rich venom more effectively degraded blood clots. Venoms with higher thrombolytic activity demonstrated an enhanced ability to target multiple sites across fibrin chains critical to clot stability and structure, as well as clot-stabilizing proteins including factor XIII, fibronectin, and vitronectin.</p><p><strong>Conclusions: </strong>Collectively, this study significantly expands our understanding of the thrombolytic and fibrinolytic effects of snake venom by determining the full suite of clot-specific venom targets that are involved in clot formation and stability. This has important implications for the treatment of snake envenomation, the bioprospecting of therapeutically useful molecules, and the development of research tools for investigating hematologic disorders.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692637","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":"Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH: reply","authors":"Jerrold H. Levy ,&nbsp;Joseph R. Shaw ,&nbsp;Jean M. Connors ,&nbsp;James Douketis ,&nbsp;Jeffrey I. Weitz","doi":"10.1016/j.jtha.2025.03.010","DOIUrl":"10.1016/j.jtha.2025.03.010","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 5","pages":"Pages 1727-1729"},"PeriodicalIF":5.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674269","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":"Trends in home treatment and early discharge of patients with low-risk pulmonary embolism.","authors":"Ioannis T Farmakis, Konstantinos C Christodoulou, Lukas Hobohm, George Giannakoulas, Karsten Keller, Philipp Lurz, Luca Valerio, Stefano Barco, Stavros V Konstantinides","doi":"10.1016/j.jtha.2025.03.007","DOIUrl":"10.1016/j.jtha.2025.03.007","url":null,"abstract":"<p><strong>Background: </strong>Recent guidelines recommend a strategy of home treatment or early discharge in low-risk pulmonary embolism (PE). Contemporary rates of the implementation of this approach in everyday clinical practice are unknown.</p><p><strong>Objective: </strong>To determine the proportion of patients with PE who fulfill eligibility criteria for home treatment or early discharge, to investigate in how many of them such a management strategy is actually followed, and to discover differences in early complications between early or later discharge among low-risk patients.</p><p><strong>Methods: </strong>Based on the United States Nationwide Emergency Department Sample and Nationwide Readmission Database, we identified low-risk PE patients (absence of hemodynamic instability, cor pulmonale, tachycardia, dyspnea, hypothermia, altered mental status, and fulfillment of the Hestia criteria). We analyzed the proportion of direct or early (<48 hours) discharge and the association with demographic and clinical variables. We also studied the 90-day occurrence of venous thromboembolism recurrence and major bleeding.</p><p><strong>Results: </strong>From 2016 to 2020, 641 621 (30.6%) of 2 099 390 PE cases in the Nationwide Emergency Department Sample database were low risk. Among low-risk PE, 31.5% received home treatment compared with 15.4% of those not classified as low risk. Home treatment for low-risk patients showed an increasing trend over time. In the Nationwide Readmission Database, 481 321 (24.7%) of 1 950 708 PE hospitalizations were classified as low risk. An early discharge strategy was followed in 22.6% of all cases, increasing to 45.9% for low-risk PE admissions, with a rising trend observed from 2016. Factors associated with home treatment or early discharge among low-risk patients included age, sex, and absence of comorbidities. Ninety-day incidence of venous thromboembolism recurrence and major bleeding was low among low-risk patients with early discharge (1.3% and 1.5%, respectively).</p><p><strong>Conclusion: </strong>There is an increasing adoption of home treatment and early discharge for low-risk PE in routine practice. This approach appears safe, supporting findings from previous trials.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663690","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 risk determined by CREB3L1 variants in a population-based cohort study: linkage disequilibrium with prothrombin mutation.","authors":"Eric Manderstedt, Christer Halldén, Christina Lind-Halldén, Johan Elf, Peter J Svensson, Gunnar Engström, Olle Melander, Aris Baras, Luca A Lotta, Bengt Zöller","doi":"10.1016/j.jtha.2025.02.041","DOIUrl":"10.1016/j.jtha.2025.02.041","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663686","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":"Corticosteroid use to mitigate transaminitis-associated decline in FVIII levels following valoctocogene roxaparvovec gene therapy: clinical practice guidance.","authors":"Barbara A Konkle, Flora Peyvandi, Graham R Foster, Cedric Hermans, Vincenzo La Mura, Andrew D Leavitt, David Lillicrap, Johnny Mahlangu, Margareth C Ozelo, Steven Pipe, Michael Recht, Alok Srivastava, Guy Young, Wolfgang Miesbach","doi":"10.1016/j.jtha.2025.02.042","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.02.042","url":null,"abstract":"<p><p>Valoctocogene roxaparvovec is the only factor VIII (FVIII) gene therapy currently approved for adults with severe hemophilia A in Europe and the USA. Elevated alanine transaminase (transaminitis) has been the most common adverse event observed during valoctocogene roxaparvovec clinical trials. Typically mild and transient, this marker of hepatocyte injury coincides, in some patients, with reduced FVIII levels and is generally managed with a reactive course of corticosteroids. An essential step in optimizing outcomes for patients who receive valoctocogene roxaparvovec is to review the extensive evidence currently available on this topic to determine practices for managing transaminitis, if it occurs. This forum article provides practical guidance based on the available clinical data and expert opinion for evaluating and managing transaminitis with corticosteroids to mitigate potential declines in FVIII activity levels in adults with severe hemophilia A who have received valoctocogene roxaparvovec.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639727","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":"Importance of tubulin detyrosination in platelet biogenesis.","authors":"Sylvie Moog, Léa Mallo, Anita Eckly, Carsten Janke, Aurora Pujol, Pablo Iruzubieta, Adolfo López de Munain, Marie-Jo Moutin, Catherine Strassel, François Lanza, Quentin Kimmerlin","doi":"10.1016/j.jtha.2025.02.043","DOIUrl":"10.1016/j.jtha.2025.02.043","url":null,"abstract":"<p><strong>Background: </strong>The functional diversity of microtubules is regulated through the expression of distinct α- and β-tubulin isotypes together with several posttranslational modifications, a concept known as tubulin code. Tubulin detyrosination is a reversible posttranslational modification that consists of the removal of the genetically encoded C-terminal tyrosine residue of most α-tubulins. While this modification has been observed in the megakaryocyte lineage, its importance remains poorly understood in platelet biogenesis.</p><p><strong>Objectives: </strong>To assess the role of α-tubulin detyrosination in platelet biogenesis.</p><p><strong>Methods: </strong>The responsible enzymes and the relative abundance of detyrosinated α-tubulins were monitored by quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively, in human cultured megakaryocytes and platelets differentiated from CD34⁺ hematopoietic stem and progenitor cells. The function of α-tubulin detyrosination was assessed in human cultured megakaryocytes treated with the VASH-SVBP inhibitor EpoY, and in mice constitutively inactivated for Svbp (which encodes the cofactor of the VASH detyrosinases).</p><p><strong>Results: </strong>Transcriptional analysis identified VASH1-SVBP and MATCAP as the predominant detyrosinases in the megakaryocyte lineage. During megakaryocyte maturation, their transcript levels progressively increased and correlated with the accumulation of detyrosinated α-tubulins. Remarkably, inhibition of VASH1-SVBP by EpoY abolished tubulin detyrosination, establishing VASH1-SVBP as the main functional detyrosinase in megakaryocytes. More importantly, EpoY enhanced proplatelet formation and platelet production in vitro. These in vitro data were confirmed in vivo in SVBP-deficient mice, which exhibited an increase in platelet counts.</p><p><strong>Conclusion: </strong>These findings reveal, for the first time, a role for tubulin detyrosination in proplatelet formation, thereby expanding our understanding of the megakaryocyte tubulin code beyond tubulin isotypes.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639734","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":"The thrombin generation potential increases after feminizing gender-affirming hormone treatment, decreases after masculinizing gender-affirming hormone treatment, and is determined by the hormone treatment regimen.","authors":"Mette Bøgehave, Dorte Glintborg, Louise Lehmann Christensen, Guy T'Sjoen, Jeroen Vervalcke, Chantal Maria Wiepjes, Martin den Heijer, Marianne Skovsager Andersen, Else-Marie Bladbjerg","doi":"10.1016/j.jtha.2025.03.006","DOIUrl":"10.1016/j.jtha.2025.03.006","url":null,"abstract":"<p><strong>Background: </strong>The effects of gender-affirming hormone therapy (GAHT) on the overall coagulation potential are not clarified. The global thrombin generation (TG) assay addresses the combined effect of coagulation factors and inhibitors.</p><p><strong>Objectives: </strong>We aimed to investigate changes in TG after initiation of feminizing or masculinizing GAHT.</p><p><strong>Methods: </strong>We included a cohort of 270 transgender women and 348 transgender men aged >17 years. The primary outcomes were TG variables (endogenous thrombin potential [ETP], peak TG, and TG lag time) measured at baseline and after 12 months of feminizing GAHT (3 groups of oral/transdermal estradiol and cyproterone acetate) or masculinizing GAHT (7 groups of intramuscular/transdermal testosterone).</p><p><strong>Results: </strong>In transgender women, ETP and peak TG increased after oral and transdermal estradiol (P < .001), and the largest increase was after oral estradiol (ΔETP: 113 nmol/L × min, P = .011; Δpeak TG: 28 nmol/L, P = .009). In transgender men, ETP or peak TG decreased after 6 testosterone modalities (P < .05) except transdermal testosterone. The largest 12 months effect was seen in transgender men receiving gestagen at baseline compared with intramuscular testosterone (ΔETP: -199 nmol/L × min, P < .001; Δpeak TG: -38 nmol/L, P = .008) and transdermal testosterone (ΔETP: -216 nmol/L × min, P < .001; Δpeak TG: -40 nmol/L, P = .007). Lag time was prolonged for 6 testosterone modalities (P < .05), except in the subgroup receiving baseline gestagen, with no between-group differences.</p><p><strong>Conclusion: </strong>Feminizing and masculinizing GAHT for 12 months affected coagulation in opposite directions. Feminizing GAHT was procoagulant, whereas masculinizing GAHT was anticoagulant. Of note, transdermal feminizing GAHT had the least pronounced procoagulant effect.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639652","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":"Risks of incident venous thromboembolism, recurrent thromboembolism, and use of antithrombotic therapies among children with congenital heart disease undergoing cardiac surgery: a global multicenter analysis of real-world data.","authors":"Amy L Kiskaddon, Nhue L Do, Ernest K Amankwah, Daniel M Witt, Vera Ignjatovic, Therese M Giglia, Gary M Woods, Hilary B Whitworth, Arabela C Stock, Neil A Goldenberg","doi":"10.1016/j.jtha.2025.03.005","DOIUrl":"10.1016/j.jtha.2025.03.005","url":null,"abstract":"<p><strong>Background: </strong>Data on the characteristics and antithrombotic treatments of venous thromboembolism (VTE) among children with congenital heart disease undergoing cardiac surgery are limited.</p><p><strong>Objectives: </strong>We aimed to evaluate the features and rates of recurrent thromboembolism in real-world experience using a global multicenter dataset.</p><p><strong>Methods: </strong>We queried the TriNetX global electronic health record-derived real-world data research platform for patients <18 years of age who underwent cardiac surgery for congenital heart disease with a diagnosis of VTE within 1 year of surgery. Data on patient and VTE characteristics, antithrombotic therapies, and recurrent thromboembolism were descriptively analyzed.</p><p><strong>Results: </strong>Of 24 879 children, 1475 (5.9%) developed an acute incident VTE within 1 year of surgery. Lower extremity deep venous thrombosis (n = 999, 67.7%) was the most common VTE type, and the Glenn procedure was the most common surgery type (n = 432, 29.3%). Unfractionated heparin was utilized for acute (<7 days after diagnosis) and subacute (≥7 days to 3 months after diagnosis) VTE treatment in 1022 (69.3%) and 895 (60.7%) patients, respectively. The 1-year rate of recurrent thromboembolism was high (n = 372, 25%), most of which were lower extremity deep venous thrombosis (n = 305, 81.9%).</p><p><strong>Conclusion: </strong>Approximately 6% of children undergoing cardiac surgery develop VTE within 1 year. The 1-year risk of thromboembolism recurrence is 25%. Prospective multicenter studies are essential to identify factors associated with the occurrence and recurrence of VTE in children undergoing cardiac surgery. This research will provide valuable insights for future interventional trials focused on preventing incident and recurrent VTE in this vulnerable population.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639742","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":"Unconventional interaction of the zebrafish thrombopoietin receptor with Mapk14a determines thrombocyte development and function.","authors":"Kavan Jagdish Thakkar, Saadia Naseer, Shayeri Chowdhury, Sweta Mondal, Saurabh Shrivastva, Louis Ribeyron, Manoj B Menon, Vaibhav Kapuria, Shilpi Minocha, Anita Roy","doi":"10.1016/j.jtha.2025.03.004","DOIUrl":"10.1016/j.jtha.2025.03.004","url":null,"abstract":"<p><strong>Background: </strong>Thrombopoietin receptor signalling permits the thrombocyte lineage development in human, mice as well as zebrafish. While the sequence, structure, signalling, and function of TpoR is well-conserved in humans and mice, the zebrafish thrombopoietin receptor (zTpoR) remains less understood.</p><p><strong>Objectives: </strong>In this article, we identified the interactome of the cytoplasmic domain of zTpoR.</p><p><strong>Methods: </strong>Using recombinant zTpoR cytoplasmic domain, we designed a pull down assay combined with mass spectrometry to identify possible interactors of the cytoplasmic domain. We further used biochemistry, flow cytometry and zebrafish bleeding time assay to demonstrate the effects of these interactions.</p><p><strong>Results: </strong>We observed a specific interaction of the zTpoR with Mitogen-activated protein kinase14a (Mapk14a), a homolog of the human and mouse p38 Mitogen-activated protein kinaseα (p38-MAPKα). Interestingly, this interaction was not observed with human TpoR, highlighting a unique aspect of zebrafish biology. To understand the physiological consequence of zTpoR-Mapk14a interaction, we used inhibitors of Janus kinase (Jak) (ruxolitinib) and Mapk14a (BIRB 796) in zebrafish. Both ruxolitinib and BIRB 796 reduced the thrombocyte, myeloid and progenitor cell count while increasing the bleeding time. Moreover, combinatorial treatment with BIRB 796 and ruxolitinib showed an additive effect on bleeding time without any further decrease in the myeloid and progenitor cell counts.</p><p><strong>Conclusion: </strong>We thus identified and characterized a specific interaction of zTpoR with Mapk14a that regulates zebrafish thrombopoiesis in both embryonic and adult stages.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634246","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}