Journal of Thrombosis and Haemostasis最新文献

{"title":"Examining downstream effects of concizumab in hemophilia A with a mathematical modeling approach","authors":"Kenji Miyazawa ,&nbsp;Alan E. Mast ,&nbsp;Adam R. Wufsus ,&nbsp;Michael Dockal ,&nbsp;Marianne Kjalke ,&nbsp;Karin Leiderman","doi":"10.1016/j.jtha.2024.10.028","DOIUrl":"10.1016/j.jtha.2024.10.028","url":null,"abstract":"<div><h3>Background</h3><div>Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits factor (F)Xa, the TF-FVIIa-FXa complex, and early forms of the prothrombinase complex. Concizumab is a monoclonal antibody that blocks FXa inhibition by TFPI and reduces bleeding in hemophilia.</div></div><div><h3>Objectives</h3><div>To examine how concizumab impacts various reactions of TFPI to restore thrombin generation in hemophilia A using mathematical models.</div></div><div><h3>Methods</h3><div>A compartment model was used to estimate plasma concentrations of free concizumab and its complexes with TFPIα and TFPIβ. Concizumab was integrated into a flow-mediated mathematical model of coagulation, and a small injury was simulated under hemophilia A conditions. Simulations were then analyzed to determine how concizumab’s blockade of TFPI anticoagulant activities, specifically the inhibition of FXa in plasma and on platelets, inhibition of TF:FVIIa at the subendothelium, and prior sequestration of plasma TFPIα to the endothelium via TFPIβ, altered thrombin generation.</div></div><div><h3>Results</h3><div>Concizumab improved simulated thrombin generation in hemophilia A by simultaneously altering all 3 mechanisms of the TFPI anticoagulant blockade examined. Concizumab sequestered ∼75% of plasma TFPIα through the formation of ternary TFPIα-concizumab-TFPIβ-complexes. For all TF levels, reducing the TFPIα plasma concentration had the largest impact on the lag time, followed by blocking TFPIα inhibition of TF:FVIIa:FXa and subsequently by blocking TFPIα inhibition of FXa in plasma and on the platelet surface.</div></div><div><h3>Conclusion</h3><div>The effectiveness of concizumab is mediated through the blockade of TFPI anticoagulant activities in plasma and on multiple physiological surfaces. An important and previously unrecognized function of concizumab was the sequestration of plasma TFPIα to the endothelium.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 480-491"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemostatic derangements associated with cardiopulmonary bypass predict outcomes in pediatric patients undergoing corrective heart surgery","authors":"Kevin Todd ,&nbsp;Spencer J. Hogue ,&nbsp;James S. Tweddell ,&nbsp;James A. Reagor ,&nbsp;Eric Mullins ,&nbsp;Mary G. Block ,&nbsp;Leah Rosenfeldt ,&nbsp;Brenton Francisco ,&nbsp;Sonata Jodele ,&nbsp;Bal Krishan Sharma ,&nbsp;Adam Lane ,&nbsp;Craig Slusher ,&nbsp;Mousa Kharnaf ,&nbsp;David L.S. Morales ,&nbsp;Joseph S. Palumbo","doi":"10.1016/j.jtha.2024.10.029","DOIUrl":"10.1016/j.jtha.2024.10.029","url":null,"abstract":"<div><h3>Background</h3><div>Understanding of the hemostatic and complement alterations associated with cardiopulmonary bypass (CPB) in pediatric patients and the impact of these alterations on outcome is limited.</div></div><div><h3>Objectives</h3><div>The present study prospectively characterized these alterations and their association with postoperative outcomes in pediatric CPB.</div></div><div><h3>Methods</h3><div>All patients aged &lt;21 years undergoing CPB at the authors’ institution between 2020 and 2021 who weighed &gt;3 kg, were &gt;36 weeks gestational age, and had no known prothrombotic or hemorrhagic disorders were eligible. Blood samples were analyzed for multiple hemostatic and complement biomarkers pre-, intra-, and 24 hours post-CPB. Biomarker levels were compared to clinical outcomes, including chest tube output (CTO).</div></div><div><h3>Results</h3><div>Fifty consecutive patients were enrolled. CPB resulted in multiple significant alterations in hemostatic and complement components. Lower platelet counts (&lt;80 × 10⁹ platelets/L) at CPB termination were associated with increased postoperative CTO (<em>P</em> = .003). Lower factor (F)VIII levels (&lt;60 IU/dL) at the end of CPB were associated with a longer hospital stay (<em>P</em> &lt; .001) and increased postoperative CTO (<em>P</em> &lt; .001). Patients undergoing staged single ventricle reconstruction were more likely to have lower platelet counts at CPB termination (<em>P</em> = .009) and higher CTO postoperatively (<em>P</em> = .001) than patients undergoing other types of surgical repair. These differences were not due to different preoperative platelet counts, increased incidences of circulatory arrest, or longer CPB times.</div></div><div><h3>Conclusion</h3><div>These data suggest that intraoperative alterations in hemostatic system components may predict postoperative outcomes in pediatric CPB. Further study is needed to determine if interventions targeting platelets or FVIII could improve outcomes in pediatric CPB.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 492-503"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622771","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":"Corrigendum to ‘Extending Venous Thromboembolism Secondary Prevention with Apixaban in Cancer Patients. The EVE Trial’","authors":"Robert D. McBane II ,&nbsp;Charles L. Loprinzi ,&nbsp;Tyler Zemla ,&nbsp;Alfonso Tafur ,&nbsp;Kristen Sanfilippo ,&nbsp;Jane Jijun Liu ,&nbsp;David A. Garcia ,&nbsp;James Heun ,&nbsp;Krishna Gundabolu ,&nbsp;Adedayo A. Onitilo ,&nbsp;Usha Perepu ,&nbsp;Monic R. Drescher ,&nbsp;Stanislav Henkin ,&nbsp;Damon Houghton ,&nbsp;Aneel Ashrani ,&nbsp;Henny Billett ,&nbsp;Micah J. Mooberry ,&nbsp;Shaylene A. McCue ,&nbsp;Minji K. Lee ,&nbsp;Jennifer G. Le-Rademacher ,&nbsp;Waldemar E. Wysokinski","doi":"10.1016/j.jtha.2024.12.011","DOIUrl":"10.1016/j.jtha.2024.12.011","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Page 756"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872468","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":"Annoucements","authors":"","doi":"10.1016/S1538-7836(25)00041-8","DOIUrl":"10.1016/S1538-7836(25)00041-8","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Page 757"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143179417","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":"Pazopanib in treatment of hereditary hemorrhagic telangiectasia-related epistaxis and gastrointestinal bleeding","authors":"Magdalena D. Lewandowska,&nbsp;Shelby Gordon,&nbsp;Anthony Betbadal,&nbsp;Amy D. Shapiro","doi":"10.1016/j.jtha.2024.10.014","DOIUrl":"10.1016/j.jtha.2024.10.014","url":null,"abstract":"<div><h3>Background</h3><div>Hereditary hemorrhagic telangiectasia (HHT) is a bleeding disorder characterized by arteriovenous malformations, commonly presenting with epistaxis and gastrointestinal (GI) bleeding. Bleeding symptoms may be difficult to manage and may become life-threatening, with many patients developing dependence on parenteral iron and/or blood transfusion. There is a growing body of evidence that antiangiogenic therapies may be effective in management of bleeding symptoms, presumably targeting pathogenic HHT pathways such as vascular endothelial growth factor receptor.</div></div><div><h3>Objectives</h3><div>To report single-center, retrospective real-world use of pazopanib, an orally administered tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptors, in 6 patients with HHT-associated epistaxis and/or GI bleeding.</div></div><div><h3>Methods</h3><div>A retrospective observational analysis was performed to assess the safety/efficacy of pazopanib use in patients with confirmed HHT-associated epistaxis and/or GI bleeding between January 1, 2019, and June 14, 2023. The Indiana Hemophilia and Thrombosis institutional electronic medical record was queried for HHT patients who were treated with pazopanib for ≥3 months. Patient data were obtained from patient documentation, physician/nursing notes, and on-call documentation. Institutional review board approval was obtained for data pull as an exempt study.</div></div><div><h3>Results</h3><div>Our observations on the real-world use of pazopanib in 6 HHT patients with moderate-to-severe bleeding showed improvement in hemoglobin levels, with reduction in iron infusions and red blood cell transfusion requirement.</div></div><div><h3>Conclusion</h3><div>Pazopanib may be a reasonable option for patients with HHT with epistaxis or gastrointestinal bleeding that are refractory to standard treatment.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 525-530"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent splenic-derived IgMs preferentially recognize factor VIII A2 and C2 domain epitopes but do not alter antibody production","authors":"Elizabeth S. York ,&nbsp;Benjamin D. Dratch ,&nbsp;Jasmine Ito ,&nbsp;Samantha M. Horwitz ,&nbsp;Sahand Emamian ,&nbsp;Joseph A. Ambarian ,&nbsp;Surinder Gill ,&nbsp;Jayre Jones ,&nbsp;Satheesh Chonat ,&nbsp;Pete Lollar ,&nbsp;Shannon L. Meeks ,&nbsp;Katherine M. Davis ,&nbsp;Glaivy Batsuli","doi":"10.1016/j.jtha.2024.10.017","DOIUrl":"10.1016/j.jtha.2024.10.017","url":null,"abstract":"<div><h3>Background</h3><div>The most significant treatment complication for patients with hemophilia A is the development of neutralizing immunoglobins (Igs) G, termed inhibitors, against factor VIII (FVIII), which prevent FVIII replacement therapy. Low titers of FVIII-specific IgMs have been identified in hemophilia A patients with and without inhibitors, as well as in healthy individuals. However, the duration and influence of IgMs on the immune response to FVIII remains unclear.</div></div><div><h3>Objectives</h3><div>To characterize the binding interactions of persistently secreted FVIII-specific IgMs in hemophilia A mice and assess their effect on IgG antibody development.</div></div><div><h3>Methods</h3><div>Splenic-derived monoclonal antibodies (mAbs) from immunized FVIII knockout mice were isolated and purified using hybridoma technology. Binding interactions were assessed utilizing a novel fluid-phase enzyme-linked immunosorbent assay and computational modeling with High Ambiguity-Driven protein-protein DOCKing to account for weak IgM binding.</div></div><div><h3>Results</h3><div>Sixteen porcine cross-reactive and noninhibitory FVIII-specific IgM mAbs were identified. RNA sequencing of FVIII-specific IgMs revealed 13 unique variable, diversity, and joining (VDJ)/variable and joining (VJ) sequences indicating derivation from 13 unique B cell clones. The IgMs demonstrated polyclonal and polyreactive binding to FVIII <em>in vitro</em> and <em>in silico</em>. Molecular docking studies with reconstructed IgM variable, diversity, and joining/variable and joining regions identified frequent IgM interactions with amino acid residues K376, T381, K437, R2215, or K2249 within the FVIII A2 and C2 domains. Injections of individual IgMs prior to FVIII exposure and co-injection of FVIII/IgM immune complexes did not affect <em>de novo</em> FVIII antibody production.</div></div><div><h3>Conclusion</h3><div>Persistent FVIII-specific IgMs are polyclonal but preferentially bind the A2 and C2 domains. FVIII/IgM immune complex formation does not significantly alter inhibitor development.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 440-457"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546158","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":"Validating International Classification of Diseases Code 10th Revision algorithms for accurate identification of pulmonary embolism","authors":"Behnood Bikdeli ,&nbsp;Candrika D. Khairani ,&nbsp;Antoine Bejjani ,&nbsp;Ying-Chih Lo ,&nbsp;Shiwani Mahajan ,&nbsp;César Caraballo ,&nbsp;Jose Victor Jimenez ,&nbsp;Darsiya Krishnathasan ,&nbsp;Mehrdad Zarghami ,&nbsp;Sina Rashedi ,&nbsp;David Jimenez ,&nbsp;Stefano Barco ,&nbsp;Eric A. Secemsky ,&nbsp;Frederikus A. Klok ,&nbsp;Andetta R. Hunsaker ,&nbsp;Ayaz Aghayev ,&nbsp;Alfonso Muriel ,&nbsp;Mohamad A. Hussain ,&nbsp;Abena Appah-Sampong ,&nbsp;Yuan Lu ,&nbsp;Harlan M. Krumholz","doi":"10.1016/j.jtha.2024.10.013","DOIUrl":"10.1016/j.jtha.2024.10.013","url":null,"abstract":"<div><h3>Background</h3><div>Many research investigations for pulmonary embolism (PE) rely on the International Classification of Diseases 10th Revision (ICD-10) codes for analyses of electronic databases. The validity of ICD-10 codes in identifying PE remains uncertain.</div></div><div><h3>Objectives</h3><div>The objective of this study was to validate an algorithm to efficiently identify pulmonary embolism using ICD-10 codes.</div></div><div><h3>Methods</h3><div>Using a prespecified protocol, patients in the Mass General-Brigham hospitals (2016-2021) with ICD-10 principal discharge codes for PE, those with secondary codes for PE, and those without PE codes were identified (<em>n</em> = 578 from each group). Weighting was applied to represent each group proportionate to their true prevalence. The accuracy of ICD-10 codes for identifying PE was compared with adjudication by independent physicians. The F1 score, which incorporates sensitivity and positive predictive value (PPV), was assessed. Subset validation was performed at Yale-New Haven Health System.</div></div><div><h3>Results</h3><div>A total of 1712 patients were included (age: 60.6 years; 52.3% female). ICD-10 PE codes in the principal discharge position had sensitivity and PPV of 58.3% and 92.1%, respectively. Adding secondary discharge codes to the principal discharge codes improved the sensitivity to 83.2%, but the PPV was reduced to 79.1%. Using a combination of ICD-10 PE principal discharge codes or secondary codes plus imaging codes for PE led to sensitivity and PPV of 81.6% and 84.7%, respectively, and the highest F1 score (83.1%; <em>P &lt;</em> .001 compared with other methods). Validation yielded largely similar results.</div></div><div><h3>Conclusion</h3><div>Although the principal discharge codes for PE show excellent PPV, they miss 40% of acute PEs. A combination of principal discharge codes and secondary codes plus PE imaging codes led to improved sensitivity without severe reduction in PPV.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 556-564"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591030","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":"Catheter-related thrombosis in adults with cancer: a secondary analysis of a prospective randomized controlled trial","authors":"Greg Hapgood ,&nbsp;Kate Hill ,&nbsp;Satomi Okano ,&nbsp;Emad Abro ,&nbsp;David Looke ,&nbsp;Glen Kennedy ,&nbsp;Gilbert Pavilion ,&nbsp;Rosita Van Kuilenburg ,&nbsp;Alanna Geary ,&nbsp;Warren Joubert ,&nbsp;Melissa Eastgate ,&nbsp;Mark Jones ,&nbsp;Peter Mollee","doi":"10.1016/j.jtha.2024.11.002","DOIUrl":"10.1016/j.jtha.2024.11.002","url":null,"abstract":"<div><h3>Background</h3><div>Catheter-related thrombosis (CRT) is a complication of central venous access devices (CVADs). Evidence is variable regarding the significance of the side of catheter insertion. The role of the patient’s hand dominance in predisposition to CRT remains uncertain.</div></div><div><h3>Objectives</h3><div>In a prospective randomized controlled trial, adult cancer patients were randomly allocated to either dominant or nondominant side CVAD insertion. The primary endpoint of this trial examined the incidence of catheter-associated bloodstream infection. Here, we report the secondary endpoint of the incidence of CRT.</div></div><div><h3>Methods</h3><div>Six hundred forty CVADs were randomized to the dominant (<em>n</em> = 322) or nondominant (<em>n</em> = 318) side of insertion. Only symptomatic patients underwent ultrasound imaging to evaluate for CRT.</div></div><div><h3>Results</h3><div>The median patient age was 58 years, 60% of patients had hematologic malignancies and 40% had solid tumors. CVADs used were peripherally-inserted central catheter line (67%), tunneled CVAD (23%), or nontunneled CVAD (10%). The CRT incidence rate was 0.65 versus 0.82 per 1000 line days in the dominant versus nondominant group (hazard ratio [HR], 1.2; 95% CI, 0.58-2.48; <em>P</em> = .63). There was no significant difference in CRT incidence rate between left- and right-sided insertions (HR, 0.63; 95% CI, 0.30-1.32; <em>P</em> = .22). The CRT incidence rate was lower in right-handed versus left-handed line inserters (HR, 0.29; 95% CI, 0.12-0.71; <em>P</em> = .007).</div></div><div><h3>Conclusion</h3><div>The rate of CRT was not associated with whether CVAD insertion was on the patient’s dominant or nondominant side or the side of insertion. The role of inserter hand dominance requires further investigation.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 627-634"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644063","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":"Long-term FXa inhibition attenuates thromboinflammation after acute myocardial infarction and stroke by platelet proteome alteration","authors":"Amin Polzin ,&nbsp;Marcel Benkhoff ,&nbsp;Manuela Thienel ,&nbsp;Maike Barcik ,&nbsp;Philipp Mourikis ,&nbsp;Khrystyna Shchurovska ,&nbsp;Carolin Helten ,&nbsp;Vincent Ehreiser ,&nbsp;Zhang Zhe ,&nbsp;Franziska von Wulffen ,&nbsp;Alexander Theiss ,&nbsp;Sameera Peri ,&nbsp;Sophie Cremer ,&nbsp;Samantha Ahlbrecht ,&nbsp;Saif Zako ,&nbsp;Laura Wildeis ,&nbsp;Gabrielle Al-Kassis ,&nbsp;Daniel Metzen ,&nbsp;Amelie Utz ,&nbsp;Hao Hu ,&nbsp;Tobias Petzold","doi":"10.1016/j.jtha.2024.10.025","DOIUrl":"10.1016/j.jtha.2024.10.025","url":null,"abstract":"<div><h3>Background</h3><div>Immediate activated factor (F)X (FXa) inhibition exerts direct antiplatelet effects in the context of arterial thrombosis but little is known about the impact of long-term therapy on platelet function in ischemic cardiovascular diseases.</div></div><div><h3>Objectives</h3><div>Therefore, we analyzed platelet-derived effects of long-term FXa inhibition in the setting of acute myocardial infarction (AMI) and stroke.</div></div><div><h3>Methods</h3><div>We evaluated the effect of acute versus chronic FXa inhibition on thromboinflammation following AMI and stroke in mice <em>in vivo</em>. Mechanistically, we identified changes in platelet gene expression and proteome under chronic FXa nonvitamin K antagonist oral anticoagulant treatment and characterized its functional consequence on platelet physiology. In a prospectively recruited cohort of patients with AMI, we determined cardiovascular magnetic resonance based cardiac endpoints under FXa nonvitamin K antagonist oral anticoagulant effects on clinical endpoints in a cohort of patients with AMI.</div></div><div><h3>Results</h3><div>Chronic but not acute FXa inhibition reduced cerebral and myocardial infarct size and improved cardiac function 24 hours after AMI in mice. Mechanistically, we identified an attenuated thromboinflammatory response with reduced neutrophil extracellular trap formation in mice and patient samples. Proteome and RNA expression analysis of FXa inhibitor treated patients revealed a reduction of key regulators within the membrane trafficking and secretion machinery hampering platelet α and dense granule release. Subsequent, thromboinflammatory neutrophil extracellular trap density in thrombi isolated from stroke and myocardial infarction patients was reduced. Patients with AMI treated with FXa inhibitors showed decreased infarct size after myocardial infarction compared to patients without anticoagulation treatment.</div></div><div><h3>Conclusion</h3><div>Long-term FXa inhibition induces antithromboinflammatory proteome signatures in platelets, improving infarct size after myocardial infarction and stroke.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 668-683"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world safety and efficacy of rADAMTS13 in the treatment of congenital thrombotic thrombocytopenic purpura in pediatric patients in Poland","authors":"Pawel Laguna ,&nbsp;Maria Szczepanska ,&nbsp;Magdalena Wojdalska ,&nbsp;Halina Bobrowska ,&nbsp;Joanna Kulik ,&nbsp;Danuta Pietrys ,&nbsp;Walentyna Balwierz ,&nbsp;Elzbieta Trembecka-Dubel ,&nbsp;Wojciech Mlynarski ,&nbsp;Aleksandra Laguna","doi":"10.1016/j.jtha.2024.11.008","DOIUrl":"10.1016/j.jtha.2024.11.008","url":null,"abstract":"<div><h3>Background</h3><div>Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultrarare microvascular disease caused by the deficiency of the metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motifs 13). Approximately half of all cases remain undiagnosed until a triggering event in adulthood; therefore, the prevalence rates may be underestimated. The current standard of care is based on regular transfusions of fresh frozen plasma, which often lead to allergic reactions in patients. Recombinant ADAMTS13 (rADAMTS13) is a novel treatment for cTTP, which has been approved for use in the USA, Europe, and Japan.</div></div><div><h3>Objectives</h3><div>The primary objective of this real-world data collection was to comprehensively analyze the clinical data of pediatric patients with cTTP and to provide real-world evidence of the effectiveness of rADAMTS13 treatment in the pediatric population.</div></div><div><h3>Methods</h3><div>Nine pediatric patients with cTTP were treated with an intravenous infusion of rADAMTS13 every 2 weeks.</div></div><div><h3>Results</h3><div>The results showed an increase in platelet count and a decrease in lactate dehydrogenase levels compared with baseline. None of the patients experienced any adverse events or complications as a result of treatment. Patients reported an improved quality of life due to fewer hospital visits and a reduced number of recurrent episodes of cTTP.</div></div><div><h3>Conclusion</h3><div>Treatment with rADAMTS13 resulted in the normalization of laboratory parameters in all pediatric patients with cTTP.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 635-640"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}