{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T17:44:25Z","timestamp":1740159865338,"version":"3.37.3"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"SYMPHONY","award":["NWA.1160.18.038"],"award-info":[{"award-number":["NWA.1160.18.038"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Drug Metab Pharmacokinet"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1007\/s13318-024-00876-6","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T09:02:05Z","timestamp":1708160525000},"page":"191-205","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic\u2013Pharmacodynamic Modelling in Hemophilia A: Relating Thrombin and Plasmin Generation to Factor VIII Activity After Administration of a VWF\/FVIII Concentrate"],"prefix":"10.1007","volume":"49","author":[{"given":"Lars L. F. G.","family":"Valke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2810-1570","authenticated-orcid":false,"given":"Michael E.","family":"Cloesmeijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Mansouritorghabeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wideke","family":"Barteling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole M. A.","family":"Blijlevens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjon H.","family":"Cnossen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron A. A.","family":"Math\u00f4t","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia E. M.","family":"Schols","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waander L.","family":"van Heerde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"issue":"23","key":"876_CR1","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1056\/NEJM200106073442307","volume":"344","author":"PM Mannucci","year":"2001","unstructured":"Mannucci PM, Tuddenham EG. The hemophilias\u2014from royal genes to gene therapy. N Engl J Med. 2001;344(23):1773\u20139.","journal-title":"N Engl J Med"},{"issue":"13","key":"876_CR2","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1182\/blood-2015-01-528414","volume":"125","author":"J Oldenburg","year":"2015","unstructured":"Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood. 2015;125(13):2038\u201344.","journal-title":"Blood"},{"issue":"Suppl 6","key":"876_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/hae.14046","volume":"26","author":"A Srivastava","year":"2020","unstructured":"Srivastava A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1\u2013158.","journal-title":"Haemophilia"},{"issue":"9","key":"876_CR4","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/NEJMoa1703068","volume":"377","author":"J Oldenburg","year":"2017","unstructured":"Oldenburg J, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809\u201318.","journal-title":"N Engl J Med"},{"issue":"4","key":"876_CR5","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.blre.2013.06.002","volume":"27","author":"M Franchini","year":"2013","unstructured":"Franchini M, Mannucci PM. Hemophilia A in the third millennium. Blood Rev. 2013;27(4):179\u201384.","journal-title":"Blood Rev"},{"issue":"1","key":"876_CR6","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1182\/asheducation-2017.1.595","volume":"2017","author":"A Iorio","year":"2017","unstructured":"Iorio A. Using pharmacokinetics to individualize hemophilia therapy. Hematol Am Soc Hematol Educ Program. 2017;2017(1):595\u2013604.","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"3","key":"876_CR7","doi-asserted-by":"publisher","first-page":"e170","DOI":"10.1111\/hae.13215","volume":"23","author":"A Iorio","year":"2017","unstructured":"Iorio A, et al. Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement. Haemophilia. 2017;23(3):e170\u20139.","journal-title":"Haemophilia"},{"issue":"4","key":"876_CR8","doi-asserted-by":"publisher","DOI":"10.2196\/resprot.6558","volume":"5","author":"A Iorio","year":"2016","unstructured":"Iorio A, et al. Development of a web-accessible population pharmacokinetic service-hemophilia (WAPPS-Hemo): study protocol. JMIR Res Protoc. 2016;5(4): e239.","journal-title":"JMIR Res Protoc"},{"issue":"3","key":"876_CR9","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1055\/s-0039-1677700","volume":"119","author":"M Stemberger","year":"2019","unstructured":"Stemberger M, et al. Impact of adopting population pharmacokinetics for tailoring prophylaxis in haemophilia A patients: a historically controlled observational study. Thromb Haemost. 2019;119(3):368\u201376.","journal-title":"Thromb Haemost"},{"issue":"3","key":"876_CR10","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1002\/rth2.12204","volume":"3","author":"JK Yu","year":"2019","unstructured":"Yu JK, et al. Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: a scoping review. Res Pract Thromb Haemost. 2019;3(3):528\u201341.","journal-title":"Res Pract Thromb Haemost"},{"key":"876_CR11","doi-asserted-by":"publisher","first-page":"107602961986205","DOI":"10.1177\/1076029619862052","volume":"25","author":"JY Zhou","year":"2019","unstructured":"Zhou JY, et al. Joint bleeding tendencies in adult patients with hemophilia: it\u2019s not all pharmacokinetics. Clin Appl Thromb Hemost. 2019;25:1076029619862052.","journal-title":"Clin Appl Thromb Hemost"},{"issue":"6","key":"876_CR12","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.thromres.2011.12.006","volume":"129","author":"M van Geffen","year":"2012","unstructured":"van Geffen M, van Heerde WL. Global haemostasis assays, from bench to bedside. Thromb Res. 2012;129(6):681\u20137.","journal-title":"Thromb Res"},{"issue":"3","key":"876_CR13","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1160\/TH04-10-0706","volume":"93","author":"Y Dargaud","year":"2005","unstructured":"Dargaud Y, et al. Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B. Thromb Haemost. 2005;93(3):475\u201380.","journal-title":"Thromb Haemost"},{"issue":"4","key":"876_CR14","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1111\/hae.13493","volume":"24","author":"Y Dargaud","year":"2018","unstructured":"Dargaud Y, et al. Individual thrombin generation and spontaneous bleeding rate during personalized prophylaxis with Nuwiq((R)) (human-cl rhFVIII) in previously treated patients with severe haemophilia A. Haemophilia. 2018;24(4):619\u201327.","journal-title":"Haemophilia"},{"issue":"4","key":"876_CR15","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1111\/j.1365-2516.2005.01107.x","volume":"11","author":"CP Beltran-Miranda","year":"2005","unstructured":"Beltran-Miranda CP, et al. Thrombin generation and phenotypic correlation in haemophilia A. Haemophilia. 2005;11(4):326\u201334.","journal-title":"Haemophilia"},{"issue":"6","key":"876_CR16","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1111\/bcp.15185","volume":"88","author":"LH Bukkems","year":"2022","unstructured":"Bukkems LH, et al. Combining factor VIII levels and thrombin\/plasmin generation: a population pharmacokinetic\u2013pharmacodynamic model for patients with haemophilia A. Br J Clin Pharmacol. 2022;88(6):2757\u201368.","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"876_CR17","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/hae.13935","volume":"26","author":"X Delavenne","year":"2020","unstructured":"Delavenne X, et al. A new paradigm for personalized prophylaxis for patients with severe haemophilia A. Haemophilia. 2020;26(2):228\u201335.","journal-title":"Haemophilia"},{"issue":"6","key":"876_CR18","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1179\/102453311X13085644680348","volume":"16","author":"M van Geffen","year":"2011","unstructured":"van Geffen M, et al. A novel hemostasis assay for the simultaneous measurement of coagulation and fibrinolysis. Hematology. 2011;16(6):327\u201336.","journal-title":"Hematology"},{"issue":"12","key":"876_CR19","doi-asserted-by":"publisher","first-page":"3222","DOI":"10.1111\/jth.15106","volume":"18","author":"L Valke","year":"2020","unstructured":"Valke L, et al. Pharmacodynamic monitoring of factor VIII replacement therapy in hemophilia A: combining thrombin and plasmin generation. J Thromb Haemost. 2020;18(12):3222\u201331.","journal-title":"J Thromb Haemost"},{"issue":"2","key":"876_CR20","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1055\/s-0038-1653759","volume":"73","author":"B Verbruggen","year":"1995","unstructured":"Verbruggen B, et al. The Nijmegen modification of the Bethesda assay for factor VIII: C inhibitors: improved specificity and reliability. Thromb Haemost. 1995;73(2):247\u201351.","journal-title":"Thromb Haemost"},{"issue":"8","key":"876_CR21","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12799","volume":"6","author":"C Ketteler","year":"2022","unstructured":"Ketteler C, et al. Impact of different factor VIII inhibitor kinetic profiles on the inhibitor titer quantification using the modified Nijmegen-Bethesda assay. Res Pract Thromb Haemost. 2022;6(8): e12799.","journal-title":"Res Pract Thromb Haemost"},{"issue":"4","key":"876_CR22","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1111\/j.1538-7836.2012.04645.x","volume":"10","author":"M Dardikh","year":"2012","unstructured":"Dardikh M, et al. Low-titre inhibitors, undetectable by the Nijmegen assay, reduce factor VIII half-life after immune tolerance induction. J Thromb Haemost. 2012;10(4):706\u20138.","journal-title":"J Thromb Haemost"},{"issue":"4","key":"876_CR23","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/BF01060893","volume":"9","author":"LB Sheiner","year":"1981","unstructured":"Sheiner LB, Beal SL. Some suggestions for measuring predictive performance. J Pharmacokinet Biopharm. 1981;9(4):503\u201312.","journal-title":"J Pharmacokinet Biopharm"},{"issue":"2","key":"876_CR24","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1002\/psp4.12161","volume":"6","author":"TH Nguyen","year":"2017","unstructured":"Nguyen TH, et al. Model evaluation of continuous data pharmacometric models: metrics and graphics. CPT Pharmacometrics Syst Pharmacol. 2017;6(2):87\u2013109.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"5","key":"876_CR25","doi-asserted-by":"publisher","first-page":"e474","DOI":"10.1111\/hae.13052","volume":"22","author":"M Takeyama","year":"2016","unstructured":"Takeyama M, Nogami K, Shima M. A new parameter in the thrombin generation assay, mean velocity to peak thrombin, reflects factor VIII activity in patients with haemophilia A. Haemophilia. 2016;22(5):e474\u20137.","journal-title":"Haemophilia"},{"issue":"8","key":"876_CR26","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1111\/jth.13743","volume":"15","author":"Y Dargaud","year":"2017","unstructured":"Dargaud Y, et al. Proposal for standardized preanalytical and analytical conditions for measuring thrombin generation in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2017;15(8):1704\u20137.","journal-title":"J Thromb Haemost"},{"issue":"10","key":"876_CR27","doi-asserted-by":"publisher","first-page":"3815","DOI":"10.1182\/blood.V88.10.3815.bloodjournal88103815","volume":"88","author":"GJ Broze Jr","year":"1996","unstructured":"Broze GJ Jr, Higuchi DA. Coagulation-dependent inhibition of fibrinolysis: role of carboxypeptidase-U and the premature lysis of clots from hemophilic plasma. Blood. 1996;88(10):3815\u201323.","journal-title":"Blood"},{"issue":"4","key":"876_CR28","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1055\/s-0037-1616530","volume":"86","author":"LO Mosnier","year":"2001","unstructured":"Mosnier LO, et al. The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration. Thromb Haemost. 2001;86(4):1035\u20139.","journal-title":"Thromb Haemost"},{"issue":"4","key":"876_CR29","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.thromres.2010.12.011","volume":"127","author":"ML Simpson","year":"2011","unstructured":"Simpson ML, et al. Simultaneous thrombin and plasmin generation capacities in normal and abnormal states of coagulation and fibrinolysis in children and adults. Thromb Res. 2011;127(4):317\u201323.","journal-title":"Thromb Res"},{"issue":"4","key":"876_CR30","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1160\/TH13-04-0345","volume":"110","author":"T Matsumoto","year":"2013","unstructured":"Matsumoto T, Nogami K, Shima M. Simultaneous measurement of thrombin and plasmin generation to assess the interplay between coagulation and fibrinolysis. Thromb Haemost. 2013;110(4):761\u20138.","journal-title":"Thromb Haemost"},{"key":"876_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173764","volume":"891","author":"S Atsou","year":"2021","unstructured":"Atsou S, et al. Pharmacodynamics of eftrenonacog-alfa (rFIX-Fc) in severe hemophilia B patients: a real-life study. Eur J Pharmacol. 2021;891: 173764.","journal-title":"Eur J Pharmacol"},{"issue":"4","key":"876_CR32","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1111\/jth.15640","volume":"20","author":"MJA Verhagen","year":"2022","unstructured":"Verhagen MJA, Valke L, Schols SEM. Thrombin generation for monitoring hemostatic therapy in hemophilia A: a narrative review. J Thromb Haemost. 2022;20(4):794\u2013805.","journal-title":"J Thromb Haemost"},{"issue":"2","key":"876_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.100062","volume":"7","author":"MJA Verhagen","year":"2023","unstructured":"Verhagen MJA, et al. In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype. Res Pract Thromb Haemost. 2023;7(2): 100062.","journal-title":"Res Pract Thromb Haemost"}],"container-title":["European Journal of Drug Metabolism and Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-024-00876-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13318-024-00876-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13318-024-00876-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T14:18:34Z","timestamp":1709216314000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13318-024-00876-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,17]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["876"],"URL":"https:\/\/doi.org\/10.1007\/s13318-024-00876-6","relation":{},"ISSN":["0378-7966","2107-0180"],"issn-type":[{"type":"print","value":"0378-7966"},{"type":"electronic","value":"2107-0180"}],"subject":[],"published":{"date-parts":[[2024,2,17]]},"assertion":[{"value":"16 January 2024","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2024","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"MC was funded by a grant from the Netherlands Organisation for Scientific Research (NWO) in the framework of the NWA-ORC Call grant agreement NWA.1160.18.038. MHC has received grants outside the submitted work from governmental research institutes such as NWO: ZonMW and NWO-NWA and the Innovation Fund, and an unrestricted investigator initiated research grants as well as educational and travel funding from the following companies over the years: Pfizer, Baxter\/Baxalta\/Shire, Bayer Schering Pharma, CSL Behring, Sobi Biogen, Novo Nordisk, Novartis, and Nordic Pharma, and has served as a member on steering boards of Roche, Bayer, and Octapharma. All grants, awards, and fees are always collected by the institution. RM has received grants from governmental and societal research institutes such as NWO, ZonMW, and Innovation fund and unrestricted investigator research grants from Baxter, Baxalta, Shire, Takeda, Bayer, CSL Behring, and Sobi. He has served as advisor for Bayer, CSL Behring, Merck Sharp & Dohme, Baxter, Baxalta, Shire, and Takeda. All grants and fees were paid to the institution. WvH received unrestricted grants from Bayer, Takeda, Novo Nordisk, and CSL Behring. WvH is the co-founder and CSO of Enzyre BV, a Radboudumc spinoff company. LV, MC, WB, HM, NB, and SS have no conflicts of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This project was a sub-study of the IMPALA study (registered at the Dutch Trial Register, no. NL2808) and was approved by the Medical Ethics Committee of the Radboud University Medical Center on 21 July 2011 and by the regional ethics committee of Mashhad University of Medical Sciences on 9 November 2016 (no. 89-88215).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients gave written informed consent, and the study was conducted in accordance with the Declaration of Helsinki.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}