دورية أكاديمية
Heterogeneity in the half-life of factor VIII concentrate in patients with hemophilia A is due to variability in the clearance of endogenous von Willebrand factor.
| العنوان: | Heterogeneity in the half-life of factor VIII concentrate in patients with hemophilia A is due to variability in the clearance of endogenous von Willebrand factor. |
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| المؤلفون: | Elsheikh E; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Lavin M; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Heck LA; Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA., Larkin N; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Mullaney B; Haemostasis Molecular Diagnostics Laboratory, National Coagulation Centre, St. James's Hospital, Dublin, Ireland., Doherty D; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland., Kennedy M; Discipline of Physiotherapy, Trinity Centre for Health sciences, Trinity College Dublin, St James's Hospital, Dublin, Ireland., Keenan C; Haemostasis Molecular Diagnostics Laboratory, National Coagulation Centre, St. James's Hospital, Dublin, Ireland., Guest T; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland., O'Mahony B; Irish Haemophilia Society, Dublin, Ireland., Fazavana J; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland., Fallon PG; Inflammation and Immunity Research Group, Trinity Translational Medicine Institute, St James's Hospital, Trinity College Dublin, Dublin, Ireland., Preston RJS; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland., Gormley J; Discipline of Physiotherapy, Trinity Centre for Health sciences, Trinity College Dublin, St James's Hospital, Dublin, Ireland., Ryan K; National Coagulation Centre, St James's Hospital, Dublin, Ireland., O'Connell NM; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Singleton E; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Byrne M; National Coagulation Centre, St James's Hospital, Dublin, Ireland., McGowan M; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Roche S; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Doyle M; National Coagulation Centre, St James's Hospital, Dublin, Ireland., Crowley MP; Department of Haematology, Cork University Hospital, Cork, Ireland., O'Shea SI; Department of Haematology, Cork University Hospital, Cork, Ireland., Reipert BM; IMC University of Applied Sciences Krems, Krems, Austria., Johnsen JM; Bloodworks Northwest Research Institute, Seattle, Washington, USA; Department of Medicine, University of Washington, Seattle, Washington, USA., Pipe SW; Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, Michigan, USA., Di Paola J; Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA., Turecek PL; Baxalta Innovations GmbH, A Member of the Takeda Group of Companies, Vienna, Austria., O'Donnell JS; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; National Coagulation Centre, St James's Hospital, Dublin, Ireland. Electronic address: jamesodonnell@rcsi.ie. |
| مؤلفون مشاركون: | iPATH study group |
| المصدر: | Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2023 May; Vol. 21 (5), pp. 1123-1134. Date of Electronic Publication: 2023 Jan 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 101170508 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7836 (Electronic) Linking ISSN: 15387836 NLM ISO Abbreviation: J Thromb Haemost Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Original Publication: Oxford : Blackwell Pub. |
| مواضيع طبية MeSH: | Hemophilia A*/diagnosis , Hemophilia A*/drug therapy , Hemostatics* , von Willebrand Diseases*, Humans ; Factor VIII/therapeutic use ; Factor VIII/metabolism ; von Willebrand Factor/metabolism ; Half-Life ; ABO Blood-Group System |
| مستخلص: | Background: Previous studies have reported marked interindividual variation in factor VIII (FVIII) clearance in patients with hemophilia (PWH) and proposed a number of factors that influence this heterogeneity. Objectives: To investigate the importance of the clearance rates of endogenous von Willebrand factor (VWF) compared with those of other FVIII half-life modifiers in adult PWH. Methods: The half-life of recombinant FVIII was determined in a cohort of 61 adult PWH. A range of reported modifiers of FVIII clearance was assessed (including plasma VWF:antigen and VWF propeptide levels; VWF-FVIII binding capacity; ABO blood group; and nonneutralizing anti-FVIII antibodies). The FVIII-binding region of the VWF gene was sequenced. Finally, the effects of variation in FVIII half-life on clinical phenotype were investigated. Results: We demonstrated that heterogeneity in the clearance of endogenous plasma VWF is a key determinant of variable FVIII half-life in PWH. Both ABO blood group and age significantly impact FVIII clearance. The effect of ABO blood group on FVIII half-life in PWH is modulated entirely through its effect on the clearance rates of endogenous VWF. In contrast, the age-related effect on FVIII clearance is, at least in part, VWF independent. In contrast to previous studies, no major effects of variation in VWF-FVIII binding affinity on FVIII clearance were observed. Although high-titer immunoglobulin G antibodies (≥1:80) were observed in 26% of PWH, these did not impact FVIII half-life. Importantly, the annual FVIII usage (IU/kg/y) was significantly (p = .0035) increased in patients with an FVIII half-life of <12 hours. Conclusion: Our data demonstrate that heterogeneity in the half-life of FVIII concentrates in patients with hemophilia A is primarily attributable to variability in the clearance of endogenous VWF. Competing Interests: Declaration of competing interests M.L. has served as a consultant for SOBI, CSL Behring, and Band Therapeutics and received indirect funding for the development of educational content from Takeda and speaker’s fees from CSL Behring and Pfizer. N.M.O’C. has acted as a principal investigator on clinical trials sponsored by Baxalta (now Takeda), Freeline, Pfizer, SOBI, and Sanofi; has received research support from SOBI and Takeda; and has received speaker’s fees and/or served on advisory boards for Freeline, Novo Nordisk, Pfizer, Roche, SOBI, Takeda, and uniQure. B.M.R. has served as a consultant for Takeda, Boehringer Ingelheim, and Novo Nordisk. P.L.T. is a full-time employee of Baxalta Innovations GmbH, a member of the Takeda group companies, and a shareholder in Takeda Pharmaceutical Company Limited. J.S.O’D has served on the speaker’s bureau for Baxter, Bayer, Novo Nordisk, SOBI, Boehringer Ingelheim, Leo Pharma, Takeda, and Octapharma; served on the advisory boards of Baxter, SOBI, Bayer, Octapharma, CSL Behring, Daiichi Sankyo, Boehringer Ingelheim, Takeda, and Pfizer; and received research grant funding awards from 3M, Baxter, Bayer, Pfizer, Shire, Takeda, 3M, and Novo Nordisk. The remaining authors declare no conflicts of interest. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ABO blood group; FVIII pharmacokinetics; factor VIII; von Willebrand factor |
| المشرفين على المادة: | 9001-27-8 (Factor VIII) 0 (von Willebrand Factor) 0 (ABO Blood-Group System) 0 (Hemostatics) |
| تواريخ الأحداث: | Date Created: 20230212 Date Completed: 20230502 Latest Revision: 20230525 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.jtha.2023.01.013 |
| PMID: | 36775768 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7836 |
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| DOI: | 10.1016/j.jtha.2023.01.013 |