{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:09:32Z","timestamp":1773047372846,"version":"3.50.1"},"reference-count":42,"publisher":"Georg Thieme Verlag KG","issue":"10","funder":[{"name":"2021 annual research grants of Swiss Hemophilia Network"},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["SNF 320030\u2013197392"],"award-info":[{"award-number":["SNF 320030\u2013197392"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:p>\n            Background\u2003Emicizumab is a bispecific antibody mimicking coagulation factor VIII (FVIII) employed to treat patients with hemophilia A (PwHA) regardless of FVIII inhibitor status. The identification of biological markers reflecting the hemostatic competence of patients under emicizumab therapy would have a great clinical value. Unfortunately, emicizumab over-corrects standard coagulation assays, precluding their use for evaluating the hemostatic correction achieved in vivo. Here, we investigated whether global coagulation assays (GCA) would allow monitoring the biological response to non-factor replacement therapy with emicizumab.<\/jats:p><jats:p>\n            Materials and Methods\u2003Six adults PwHA received a weekly dose of emicizumab of 3 mg\/kg during weeks (W) 1\u20034 and 1.5 mg\/kg from W5 onwards. Response to treatment was monitored weekly by emicizumab plasma concentration, thrombin generation (TG), and fibrin clot formation (FCF) and structure. TG and FCF results were compared to patient baseline, FVIII replacement, and healthy donors.<\/jats:p><jats:p>\n            Results\u2003TG and FCF significantly increased in PwHA after the loading period, reaching a plateau that lasted until the end of monitoring. Similarly, fibrin clot network became denser with thinner fibrin fibers. However, TG contrary to FCF remained at the lower limits of reference values. Remarkably, despite having similar plateau concentrations of emicizumab some patients showed markedly different degrees of TG and FCF improvement.<\/jats:p><jats:p>\n            Conclusion\u2003Our study enriches the knowledge on the use of GCA to monitor non-factor replacement therapy, indicating that TG and FCF could act as direct markers of emicizumab biological activity. GCA allow to capture and visualize the individually variable response to emicizumab, leading a step forward to the personalization of patient treatment.<\/jats:p>","DOI":"10.1055\/s-0043-1769788","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T23:08:40Z","timestamp":1687216120000},"page":"955-965","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacodynamics Monitoring of Emicizumab in Patients with Hemophilia A"],"prefix":"10.1055","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-4974","authenticated-orcid":false,"given":"Debora","family":"Bertaggia Calderara","sequence":"additional","affiliation":[{"name":"Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8258-9319","authenticated-orcid":false,"given":"Rita","family":"Marchi Cappelletti","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9806-5758","authenticated-orcid":false,"given":"Ana Patricia","family":"Batista Mesquita Sauvage","sequence":"additional","affiliation":[{"name":"Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9772-8406","authenticated-orcid":false,"given":"St\u00e9phane","family":"Durual","sequence":"additional","affiliation":[{"name":"Biomaterials Laboratory, University Clinics of Dental Medicine, University of Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8816-037X","authenticated-orcid":false,"given":"Francisco J.","family":"Gomez","sequence":"additional","affiliation":[{"name":"Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9298-8268","authenticated-orcid":false,"given":"Maxime G.","family":"Zermatten","sequence":"additional","affiliation":[{"name":"Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9382-138X","authenticated-orcid":false,"given":"Alessandro","family":"Aliotta","sequence":"additional","affiliation":[{"name":"Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7910-933X","authenticated-orcid":false,"given":"Alessandro","family":"Casini","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Geneva, Geneva, Switzerland"},{"name":"Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9686-9920","authenticated-orcid":false,"given":"Lorenzo","family":"Alberio","sequence":"additional","affiliation":[{"name":"Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,6,19]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/17474086.2018.1419862","article-title":"A contemporary look at FVIII inhibitor development: still a great influence on the evolution of hemophilia therapies","volume":"11","author":"E Santagostino","year":"2018","journal-title":"Expert Rev Hematol"},{"issue":"10","key":"ref3","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/nm.2942","article-title":"A bispecific antibody to 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Mahlangu","year":"2018","journal-title":"N Engl J Med"},{"issue":"06","key":"ref7","doi-asserted-by":"crossref","first-page":"e295","DOI":"10.1016\/S2352-3026(19)30054-7","article-title":"Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study","volume":"6","author":"S W Pipe","year":"2019","journal-title":"Lancet Haematol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2147\/JBM.S175952","article-title":"Spotlight on emicizumab in the management of hemophilia A: patient selection and special considerations","volume":"10","author":"K Yada","year":"2019","journal-title":"J Blood Med"},{"issue":"19","key":"ref9","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.3390\/jcm10194303","article-title":"Real-world data on bleeding patterns of hemophilia A patients treated with emicizumab","volume":"10","author":"S 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Dargaud","year":"2018","journal-title":"Haematologica"},{"issue":"02","key":"ref19","doi-asserted-by":"crossref","first-page":"e121","DOI":"10.1111\/hae.13689","article-title":"Use of global assays to monitor emicizumab prophylactic therapy in patients with haemophilia A with inhibitors","volume":"25","author":"D F Brophy","year":"2019","journal-title":"Haemophilia"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/hae.14318","article-title":"Emicizumab prophylaxis: prospective longitudinal real-world follow-up and monitoring","volume":"27","author":"A A Barg","year":"2021","journal-title":"Haemophilia"},{"issue":"02","key":"ref21","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/bjh.16964","article-title":"Emicizumab treatment and monitoring in a paediatric cohort: real-world data","volume":"191","author":"A A Barg","year":"2020","journal-title":"Br J 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Fibrinolysis"},{"issue":"05","key":"ref31","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/jth.13656","article-title":"Development of Shiny app tools to simplify and standardize the analysis of hemostasis assay data: communication from the SSC of the ISTH","volume":"15","author":"C Longstaff","year":"2017","journal-title":"J Thromb Haemost"},{"issue":"10","key":"ref32","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1111\/j.1538-7836.2012.04883.x","article-title":"An international study on the standardization of fibrin clot permeability measurement: methodological considerations and implications for healthy control values","volume":"10","author":"M Pieters","year":"2012","journal-title":"J Thromb Haemost"},{"issue":"21","key":"ref34","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1056\/NEJMoa1511769","article-title":"Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A","volume":"374","author":"M Shima","year":"2016","journal-title":"N Engl J Med"},{"issue":"09","key":"ref35","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1007\/s40262-017-0616-3","article-title":"A pharmacometric approach to substitute for a conventional dose-finding study in rare diseases: example of phase III dose selection for emicizumab in hemophilia A","volume":"57","author":"K Yoneyama","year":"2018","journal-title":"Clin Pharmacokinet"},{"issue":"05","key":"ref36","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/hae.14359","article-title":"Determining the approximate factor VIII level of patients with severe haemophilia A on emicizumab using in vivo global haemostasis assays","volume":"27","author":"H Kizilocak","year":"2021","journal-title":"Haemophilia"},{"issue":"23","key":"ref37","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1182\/blood-2017-08-801662","article-title":"Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII?","volume":"130","author":"P J Lenting","year":"2017","journal-title":"Blood"},{"issue":"03","key":"ref38","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1055\/s-0040-1717114","article-title":"Pharmacokinetics and pharmacodynamics of emicizumab in persons with hemophilia A with factor VIII inhibitors: HAVEN 1 study","volume":"121","author":"C Schmitt","year":"2021","journal-title":"Thromb Haemost"},{"issue":"07","key":"ref39","doi-asserted-by":"crossref","first-page":"e29731","DOI":"10.1002\/pbc.29731","article-title":"Heterogeneous coagulant potential of emicizumab in neonatal factor VIII-deficient plasma","volume":"69","author":"M Takeyama","year":"2022","journal-title":"Pediatr Blood Cancer"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/hae.14524","article-title":"Emicizumab state-of-the-art update","volume":"28","author":"J Mahlangu","year":"2022","journal-title":"Haemophilia"},{"issue":"22","key":"ref41","first-page":"2194","article-title":"Emicizumab prophylaxis in hemophilia A with inhibitors","volume":"377","author":"J Oldenburg","year":"2017","journal-title":"N Engl J Med"},{"issue":"07","key":"ref42","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/jth.14430","article-title":"Intrinsic differences between FVIIIa mimetic bispecific antibodies and FVIII prevent assignment of FVIII-equivalence","volume":"17","author":"N C Leksa","year":"2019","journal-title":"J Thromb Haemost"},{"issue":"08","key":"ref43","doi-asserted-by":"crossref","first-page":"e380","DOI":"10.3324\/haematol.2018.215129","article-title":"Rescue factor VIII replacement to secure hemostasis in a patient with hemophilia A and inhibitors on emicizumab prophylaxis undergoing hip replacement","volume":"104","author":"E Santagostino","year":"2019","journal-title":"Haematologica"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1111\/jth.14203","article-title":"In vitro studies show synergistic effects of a procoagulant bispecific antibody and bypassing agents","volume":"16","author":"R Hartmann","year":"2018","journal-title":"J Thromb Haemost"}],"container-title":["Thrombosis and 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