Considerations on activity assay discrepancies in factor VIII and factor IX products.
factor IX
factor VIII
hemophilia A
hemophilia B
hemostasis
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
28
05
2021
received:
25
01
2021
accepted:
15
06
2021
pubmed:
20
6
2021
medline:
26
10
2021
entrez:
19
6
2021
Statut:
ppublish
Résumé
New modified coagulation factor VIII (FVIII) and factor IX (FIX) products have been designed to improve the treatment of individuals with hemophilia A and B by increasing the interval between dosing. Although these FVIII and FIX molecules have been structurally modified to improve the circulation time, the changes have also influenced their behavior in functional assays in comparison with traditional plasma-derived or recombinant coagulation factors. The assignment of potencies for these products can be problematic because discordance in factor activity values between the commonly used one-stage clotting and chromogenic substrate assays is often observed. Discrepancies in potency assay values also exist when different assay kits and reagents are used in the same assay type. Ideally, all FVIII and FIX products should be calibrated against the World Health Organization (WHO) International Standards (IS) because the assignment of potencies in international units (IU) helps maintain treatment tradition and meaningful references for manufacturers, patients, and clinicians. The discrepant measurements, attributed to the modified structural and functional properties of these products, are manifested in their lack of commutability with the WHO IS for FVIII or FIX. Herein, we discuss the considerations upon which an assay is chosen for potency assignment and postadministration monitoring of a new factor product, which include the validity of the assay calibrated with the IS, the meaning of the potency values in IU, standards of care for patients, clinical relevance between the assigned potency value and recovery value from clinical laboratories, and patient safety.
Identifiants
pubmed: 34145730
doi: 10.1111/jth.15425
pii: S1538-7836(22)01892-X
doi:
Substances chimiques
Chromogenic Compounds
0
Factor VIII
9001-27-8
Factor IX
9001-28-9
Types de publication
Journal Article
Research Support, U.S. Gov't, P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2102-2111Informations de copyright
Published 2021. This article is a U.S. Government work and is in the public domain in the USA.
Références
Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia. Haemophilia. 2020;26(Suppl 6):1-158.
Den Uijl IEM, Mauser Bunschoten EP, Roosendaal G, et al. Clinical severity of haemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011;17(6):849-853.
Collins PW, Blanchette VS, Fischer K, et al. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost. 2009;7(3):413-420.
den Uijl IEM, Fischer K, Van Der Bom JG, Grobbee DE, Rosendaal FR, Plug I. Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levels. Haemophilia. 2011;17(1):41-44.
Nilsson IM, Berntorp E, Lofqvist T, Pettersson H. Twenty-five years’ experience of prophylactic treatment in severe haemophilia A and B. J Intern Med. 1992;232(1):25-32.
Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood. 2015;125(13):2038-2044.
Raut S, Hubbard AR. International reference standards in coagulation. Biologicals. 2010;38(4):423-429.
Kirkwood TB, Barrowcliffe TW. Discrepancy between one-stage and two-stage assay of factor VIII:C. Br J Haematol. 1978;40(2):333-338.
Raut S, Heath AB, Barrowcliffe TW. A collaborative study to establish the 6th International Standard for factor VIII concentrate. Thromb Haemost. 2001;85(6):1071-1078.
Hubbard AR, Heath AB. Standardization of factor VIII and von Willebrand factor in plasma: calibration of the WHO 5th International Standard (02/150). J Thromb Haemost. 2004;2(8):1380-1384.
Ovanesov MV, Williams SC, Nubling CM, et al. Summary of the WHO hearing on the development of product-specific reference materials for coagulation factor VIII and factor IX products. Biologicals. 2020;67:88-93.
Gray E, Kitchen S, Bowyer A, et al. Laboratory measurement of factor replacement therapies in the treatment of congenital haemophilia: a United Kingdom Haemophilia Centre Doctors’ Organisation guideline. Haemophilia. 2020;26(1):6-16.
Marlar RA, Strandberg K, Shima M, Adcock DM. Clinical utility and impact of the use of the chromogenic vs one-stage factor activity assays in haemophilia A and B. Eur J Haematol. 2020;104(1):3-14.
Wilmot HV, Rakowski K, Gray E. The traceability of commercial plasma calibrators to the plasma International Standards for factor VIII and factor IX. Int J Lab Hematol. 2020;42(6):810-818.
U.S. FDA. Untitled Letter. ReFacto® Antihemophilic Factor (Recombinant). 2008. Available from: https://wayback.archive-it.org/7993/20170406144900/; https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ComplianceActivities/Enforcement/UntitledLetters/ucm093445.htm.Accessed 5 January, 2021.
Peyvandi F, Kenet G, Pekrul I, Pruthi RK, Ramge P, Spannagl M. Laboratory testing in hemophilia: impact of factor and non-factor replacement therapy on coagulation assays. J Thromb Haemost. 2020;18(6):1242-1255.
Langdell RD, Wagner RH, Brinkhous KM. Effect of antihemophilic factor on one-stage clotting tests; a presumptive test for hemophilia and a simple one-stage antihemophilic factor assay procedure. J Lab Clin Med. 1953;41(4):637-647.
Mackie I, Cooper P, Lawrie A, et al. Guidelines on the laboratory aspects of assays used in haemostasis and thrombosis. Int J Lab Hematol. 2013;35(1):1-13.
Rasmussen KL, Philips M, Tripodi A, Goetze JP. Unexpected, isolated activated partial thromboplastin time prolongation: a practical mini-review. Eur J Haematol. 2020;104(6):519-525.
Rosen S. Assay of factor VIII: C with a chromogenic substrate. Scand J Haematol Suppl. 1984;40:139-145.
Rosen S, Andersson M, Blomback M, et al. Clinical application of a chromogenic substrate method for determination of factor VIII activity. Thromb Haemost. 1985;54(4):818-823.
Kihlberg K, Strandberg K, Rosen S, Ljung R, Astermark J. Discrepancies between the one-stage clotting assay and the chromogenic assay in haemophilia B. Haemophilia. 2017;23(4):620-627.
Rosen P, Rosen S, Ezban M, Persson E. Overestimation of N-glycoPEGylated factor IX activity in a one-stage factor IX clotting assay owing to silica-mediated premature conversion to activated factor IX. J Thromb Haemost. 2016;14(7):1420-1427.
Rosen S, Bryngelhed P. FIX potency of rFIX-Albumin fusion protein is underestimated by one-stage methods using silica-based APTT reagents. Haemophilia. 2020;26(2):340-345.
Williams SC, Gray E. Activity measurements of dalcinonacog alfa. Haemophilia. 2020;26(2):346-353.
Wilmot HV, Hogwood J, Gray E. Recombinant factor IX: discrepancies between one-stage clotting and chromogenic assays. Haemophilia. 2014;20(6):891-897.
Lee CA, Kessler CM, Varon D, et al. Discrepancies in potency assessment of recombinant FVIII concentrates. Haemophilia. 1998;4(4):634-640.
Dawson NJ, Kemball-Cook G, Barrowcliffe TW. Assay discrepancies with highly purified factor VIII concentrates. Haemostasis. 1989;19(3):131-137.
Hubbard AR, Weller LJ, Bevan SA. Activation profiles of factor VIII in concentrates reflect one-stage/chromogenic potency discrepancies. Br J Haematol. 2002;117(4):957-960.
Mazurier C, Parquet-Gernez A, Goudemand M. Validation of a procedure for potency assessing of a high purity factor VIII concentrate-comparison of different factor VIII coagulant assays and effect of prediluent. Thromb Haemost. 1990;64(2):251-255.
U.S. FDA. Recombinant B-Domain-Deleted Antihemophilic Factor, ReFacto: Blood Product Advisory Committee 61st Meeting; 1998. Available from: https://wayback.archive-it.org/7993/20170404123540/; https://www.fda.gov/ohrms/dockets/ac/98/transcpt/3479t2.pdf.Accessed 5 January, 2021.
Mikaelsson M, Oswaldsson U, Jankowski MA. Measurement of factor VIII activity of B-domain deleted recombinant factor VIII. Semin Hematol. 2001;38(2 Suppl 4):13-23.
Lee CA, Kessler CM, Varon D, et al. Influence of phospholipids on the assessment of factor VIII activity. Haemophilia. 1998;4(4):646-650.
Sandberg H, Almstedt A, Brandt J, et al. Structural and functional characteristics of the B-domain-deleted recombinant factor VIII protein, r-VIII SQ. Thromb Haemost. 2001;85(1):93-100.
Courter SG, Bedrosian CL. Clinical evaluation of B-domain deleted recombinant factor VIII in previously treated patients. Semin Hematol. 2001;38(2 Suppl 4):44-51.
Health Canada. Important Safety Information about ReFacto® (moroctocog alfa), Antihemophilic Factor (Recombinant) [BDDrFVIII]. 2003. Available from: https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2003/14229a-eng.php.Accessed 5 January, 2021.
Gruppo RA, Brown D, Wilkes MM, Navickis RJ. Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis-a meta-analysis. Haemophilia. 2003;9(3):251-260.
Di Paola J, Smith MP, Klamroth R, et al. ReFacto and Advate: a single-dose, randomized, two-period crossover pharmacokinetics study in subjects with haemophilia A. Haemophilia. 2007;13(2):124-130.
Johnston A. The relevance of factor VIII (FVIII) pharmacokinetics to TDM and hemophilia a treatment: is B domain-deleted FVIII equivalent to full-length FVIII? Ther Drug Monit. 2012;34(1):110-117.
European Medicines Agency. Introduction of a change to Refacto drug product specific activity specification increase of 20% in the amount of refacto protein in each vial; 2003. Available from: https://www.ema.europa.eu/en/documents/public-statement/emea-public-statement-refacto-moroctocog-alfa-introduction-change-refacto-drug-product-specific_en.pdf.Accessed 5 January, 2021.
Lambert T, Guerois C, Gay V, et al. Factor VIII recovery after a single infusion of recalibrated ReFacto in 14 severe haemophilia A patients. Haemophilia. 2007;13(4):357-360.
Datapharm. ReFacto AF powder and solvent for solution for injection & ReFacto AF powder and solvent for solution for injection in pre-filled syringe. 2020. Available from: https://www.medicines.org.uk/emc/medicine/21767/SPC/refacto%20af%20powder%20and%20solvent%20for%20solution%20for%20injection/.Accessed 24 November, 2020.
European Medicines Agency. Assessment report for Refacto. 2009. Available from: https://www.ema.europa.eu/en/documents/variation-report/refacto-af-h-c-232-ii-0059-0068-epar-assessment-report-variation_en.pdf.Accessed 5 January, 2021.
Kitchen S, Beckmann H, Katterle Y, Bruns S, Tseneklidou-Stoeter D, Maas EM. BAY 81-8973, a full-length recombinant factor VIII: results from an international comparative laboratory field study. Haemophilia. 2016;22(3):e192-e199.
Kitchen S, Jennings I, Makris M, Kitchen DP, Woods TA, Walker ID. Factor VIII assay variability in postinfusion samples containing full length and B-domain deleted FVIII. Haemophilia. 2016;22(5):806-812.
Pickering W, Hansen M, Kjalke M, Ezban M. Factor VIII chromogenic assays can be used for potency labeling and postadministration monitoring of N8-GP. J Thromb Haemost. 2016;14(8):1579-1587.
Sommer JM, Buyue Y, Bardan S, et al. Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity. Thromb Haemost. 2014;112(5):932-940.
Sommer JM, Moore N, McGuffie-Valentine B, et al. Comparative field study evaluating the activity of recombinant factor VIII Fc fusion protein in plasma samples at clinical haemostasis laboratories. Haemophilia. 2014;20(2):294-300.
St. Ledger K, Feussner A, Kalina U, et al. International comparative field study evaluating the assay performance of AFSTYLA in plasma samples at clinical hemostasis laboratories. J Thromb Haemost. 2018;16(3):555-564.
Turecek PL, Romeder-Finger S, Apostol C, et al. A world-wide survey and field study in clinical haemostasis laboratories to evaluate FVIII: C activity assay variability of ADYNOVATE and OBIZUR in comparison with ADVATE. Haemophilia. 2016;22(6):957-965.
Hubbard AR, Dodt J, Lee T, et al. Recommendations on the potency labelling of factor VIII and factor IX concentrates. J Thromb Haemost. 2013;11(5):988-989.
Leksa NC, Aleman MM, Goodman AG, Rabinovich D, Peters R, Salas J. Intrinsic differences between FVIIIa mimetic bispecific antibodies and FVIII prevent assignment of FVIII-equivalence. J Thromb Haemost. 2019;17(7):1044-1052.
Persson E, La Cour Christoffersen C. Underestimation of N-glycoPEGylated factor IX one-stage clotting activity owing to contact activator-impaired activation. Res Pract Thromb Haemost. 2017;1(2):259-263.
National Hemophilia Foundation. Medical and Scientific Advisory Council (MASAC) Statement regarding use of various clotting factor assays to monitor factor replacement therapy. 2014. Available from: https://www.hemophilia.org/sites/default/files/document/files/masac-228.pdf.Accessed 5 January, 2021.
U.S. FDA. Prescribing Information for RIXUBIS [Coagulation Factor IX (Recombinant)]. 2013. Available from: https://www.fda.gov/media/86123/download.Accessed 5 January, 2021.
Ezban M, Hermit MB, Persson E. FIXing postinfusion monitoring: assay experiences with N9-GP (nonacog beta pegol; Refixia((R)); Rebinyn((R))). Haemophilia. 2019;25(1):154-161.
Farrugia A. Potency assessment of the new generation of coagulation factor concentrates-time for a new paradigm? Thromb Haemost. 2003;90(6):968-970.
U.S. FDA. Prescribing Information OBIZUR [Antihemophilic Factor (Recombinant), Porcine Sequence]. 2014. Available from: https://www.fda.gov/media/89987/download.Accessed 5 January, 2021.
Bowyer AE, Lowe AE, Tiefenbacher S. Laboratory issues in gene therapy and emicizumab. Haemophilia. 2021;27:142-147.
Rosen S, Tiefenbacher S, Robinson M, et al. Activity of transgene-produced B-domain deleted factor VIII in human plasma following AAV5 gene therapy. Blood. 2020;136(22):2524-2534.
U.S. FDA. Human Gene Therapy for Hemophilia: Guidance for Industry. 2020. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/human-gene-therapy-hemophilia.Accessed 5 January, 2021.
U.S. National Library of Medicine. DailyMed database. Available from: https://dailymed.nlm.nih.gov/dailymed/.Accessed 5 January, 2021.
Nichols TC, Levy H, Merricks EP, Raymer RA, Lee ML. Preclinical evaluation of a next-generation, subcutaneously administered, coagulation factor IX variant, dalcinonacog alfa. PLoS One. 2020;15(10):e0240896.
Seth Chhabra E, Liu T, Kulman J, et al. BIVV001, a new class of factor VIII replacement for hemophilia A that is independent of von Willebrand factor in primates and mice. Blood. 2020;135(17):1484-1496.
Wuschko S, Kannicht C, Solecka-Witulska BA. Novel von Willebrand factor fragments increase bioavailability and extend the half-life of subcutaneously administered simoctocog alfa in a minipig model [Abstract]. In: Invited Presentation Summaries and Submitted Abstracts of the WFH 2018 World Congress. Haemophilia. 2018;24(Suppl. 5):209-218.
Solecka-Witulska BA, Lillicrap D, Hough C, Kannicht C. A Novel Von Willebrand factor fragment acts as a chaperone to prolong the half-life of recombinant human FVIII (Simoctocog Alfa) in hemophilia a dogs and FVIII/VWF double knockout mice [abstract]. Blood. 2017;130(Suppl. 1):178.