Introduction: The one-stage clotting assay is used to measure factor IX (FIX) activity in patients' plasma samples and in FIX products for hemophilia treatment. However, the diversity of reagents and instruments has resulted in significant FIX assay variability.
Methods: The accuracy of the one-stage clotting assay to measure recombinant FIX Fc fusion protein (rFIXFc) activity was evaluated by major Japanese hemophilia treatment centers and commercial laboratories that measure factor IX activity for a majority of hemophilia B patients in Japan. Plasma-derived FIX (pdFIX) and recombinant FIX (rFIX) products were used as comparators. FIX-deficient plasma was spiked with four levels of FIX products based on label potency and measured under blinded conditions by routine one-stage clotting assay procedures in 19 participating laboratories. Interlaboratory coefficient of variation and spike recovery were calculated.
Results: Interlaboratory coefficient of variation of rFIXFc was not significantly different from that of rFIX, but appeared larger than that of pdFIX. Mean spike recovery for rFIXFc was generally comparable to rFIX and pdFIX. However, larger discrepancies between pdFIX and rFIX were observed in three of nine laboratories using ellagic acid-based activated partial thromboplastin time reagents.
Conclusion: Recombinant FIX Fc fusion protein activity was found to be similar to that of rFIX or pdFIX by the one-stage clotting assay. However, minimizing interlaboratory variability is vital for optimizing future patient care.
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| http://dx.doi.org/10.1111/ijlh.13133 | DOI Listing |
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Development and internal validation of a clinical prediction model for individualized dosing of BAY 81-8973, A full-length recombinant factor VIII, in pediatric patients with haemophilia A.
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Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 10045, China. Electronic address:
Background: As the most commonly used coagulation factor VIII (FVIII) concentrate in China, the individualized dosing prediction model of Kovaltry (BAY81-8973) is not fully investigated in pediatric patients. The prophylaxis tailored by population pharmacokinetic (PopPK) model can optimize dosing regimens.
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Gene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B.
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From the Departments of Medicine and of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.C.), and Pfizer, Collegeville (J.F., J.R.) - both in Pennsylvania; the Division of Hematology, Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey (K.K.); the Department of Hematology, Hemophilia Care and Research, Necker Hospital, Institut Imagine, Paris (L.F.); the Center for Rare Disease and Hemophilia, Taichung Veterans General Hospital, Taichung, Taiwan (J.-D.W.); the Department of Translational Medicine, Lund University, Lund, and the Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö - both in Sweden (J.A.); Instituto de Hematologia do Estado do Rio de Janeiro, Rio de Janeiro (M.H.C.), and Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas (M.C.O.) - both in Brazil; the Departments of Health Research Methods, Evidence, and Impact and of Medicine, McMaster University, Hamilton, ON (A. Iorio), and the Division of Hematology, St. Michael's Hospital, University of Toronto, Toronto (J.T.) - both in Canada; the Blood Transfusion Center, National Reference Center for Congenital Bleeding Disorders, Laiko General Hospital, Athens (O.K.-F.); Vivantes Hospital in Friedrichshain, Berlin (R.K.), and the Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, and the Center for Rare Diseases Bonn, University Clinic Bonn, Bonn (J.B.O.) - all in Germany; Indiana Hemophilia and Thrombosis Center, Indianapolis (A.D.S.); the Hemostasis and Thrombosis Unit, Division of Hematology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels (C.H.); the Division of Hematology, National Center for Child Health and Development, Tokyo (A. Ishiguro); the Departments of Medicine and of Laboratory Medicine, University of California, San Francisco, San Francisco (A.D.L.); the Faculty of Medicine and Health, Central Clinical School, and the Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, and the Department of Cell and Molecular Therapies, Royal Prince Alfred Hospital - all in Sydney (J.E.J.R.); Pfizer, New York (A.F.); Pfizer, Groton, CT (J.M.); Pfizer, Rome (F.B.); and Pfizer, Cambridge, MA (P.S.).
Article Synopsis
- Fidanacogene elaparvovec is a genetic therapy for hemophilia B that showed promising results in a phase 1-2a study, maintaining high levels of factor IX activity.* -
- In a phase 3 study involving men aged 18 to 65 with severe hemophilia B, the therapy led to a significant 71% reduction in bleeding episodes over 15 months compared to standard prophylactic treatment.* -
- Despite some participants needing glucocorticoids for side effects, the therapy was generally safe, with no serious adverse infusion events reported.*
Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life.
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Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, I 44121 Ferrara, Italy.
A compartmental pharmacokinetics (PK) analysis of new extended half-life FVIII concentrates has never been performed in a large cohort of hemophilia patients. An improved PK analysis of individual outcomes may help to tailor hemophilia replacement treatment. PK outcomes after the infusion of a standard single dose of Efmoroctocog alfa were collected from 173 patients with severe/moderately severe hemophilia A in 11 Italian hemophilia centers.
View Article and Find Full Text PDFCoagulation factors VIII and factors IX testing practices in China: Results of the 5-year external quality assessment program.
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National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China. Electronic address:
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- Results showed a consistent decrease in the inter-laboratory coefficient of variation (CV) and an increase in pass rates for FVIII and FIX testing, indicating improved testing quality across laboratories.
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Biosci Rep
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Department of Physical Chemistry, Medical University of Bialystok, Poland.
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