Factor Activity Assays for Monitoring Extended Half-Life FVIII and Factor IX Replacement Therapies

Steve Kitchen; Stefan Tiefenbacher; Robert Gosselin

doi:10.1055/s-0037-1598058

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2017; 43(03): 331-337
DOI: 10.1055/s-0037-1598058

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Factor Activity Assays for Monitoring Extended Half-Life FVIII and Factor IX Replacement Therapies

Steve Kitchen

¹Sheffield Haemophilia and Thrombosis Centre, Sheffield, United Kingdom

,

Stefan Tiefenbacher

²Colorado Coagulation, Laboratory Corporation of America® Holdings, Englewood, Colorado

,

Robert Gosselin

³Department of Pathology and Laboratory Medicine, University of California Davis Health System, Sacramento, California

› Institutsangaben

Abstract

The advent of modified factor VIII (FVIII) and factor IX (FIX) molecules with extended half-lives (EHLs) compared with native FVIII and FIX represents a major advance in the field of hemophilia care, with the potential to reduce the frequency of prophylactic injections and/or to increase the trough level prior to subsequent injections. Monitoring treatment through laboratory assays will be an important part of ensuring patient safety, including any tailoring of prophylaxis. Several approaches have been used to extend half-lives, including PEGylation, and fusion to albumin or immunoglobulin. Some of these modifications affect factor assays as routinely performed in hemophilia centers; so, laboratories will need to use FVIII and FIX assays which have been shown to be suitable on a product-by-product basis. For some products, there are marked differences between results obtained using one-stage or chromogenic assays and results obtained using different reagents in the one-stage assay. The laboratory should use an assay in which the recovery of the product closely aligns with the assay used by the pharmaceutical company to assign potency to the product, so that the units reported by the laboratory agree with those used to demonstrate efficacy of the product during clinical trials. Reported assay differences in relation to several of the EHL FVIII and FIX molecules will be reviewed in this article.

Keywords

Factor VIII assay - FIX assay - extended half-life FVIII - extended half-life FIX

Volltext

Referenzen

References>
1 Srivastava A, Brewer AK, Mauser-Bunschoten EP , et al; Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 2013; 19 (1) e1-e47
2 World Federation of Haemophilia (WFH) Hemophilia Treatment Guidelines. . Available at: http://www.wfh.org/en/resources/wfh-treatment-guidelines . Accessed September 30, 2016
3 Keeling D, Tait C, Makris M. Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. A United Kingdom Haemophilia Center Doctors' Organisation (UKHCDO) guideline approved by the British Committee for Standards in Haematology. Haemophilia 2008; 14 (4) 671-684
4 Young G, Mahlangu JN. Extended half-life clotting factor concentrates: results from published clinical trials. Haemophilia 2016; 22 (Suppl 5): 25-30
5 Dodt J, Hubbard AR, Wicks SJ , et al. Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators. Haemophilia 2015; 21 (4) 543-549
6 Kitchen S, McCraw A. 2010 Diagnosis of Haemophilia and Other Bleeding Disorders. 2nd ed. World Federation of Haemophilia. Available at: http://www.wfh.org/en/page.aspx?pid=877 (Accessed September 30, 2016)
7 Jennings I, Kitchen DP, Woods TAL, Kitchen S, Walker ID, Preston FE. Laboratory performance in the World Federation of Hemophilia EQA programme, 2003-2008. Haemophilia 2009; 15 (2) 571-577
8 Favaloro EJ, Meijer P, Jennings I , et al. Problems and solutions in laboratory testing for hemophilia. Semin Thromb Hemost 2013; 39 (7) 816-833 [Erratum in: Semin Thromb Hemost. 2014 Feb;40(1):135]
9 Kitchen S, Signer-Romero K, Key NS. Current laboratory practices in the diagnosis and management of haemophilia: a global assessment. Haemophilia 2015; 21 (4) 550-557
10 Butenas S, Parhami-Seren B, Mann KG. The influence of von Willebrand factor on factor VIII activity measurements. J Thromb Haemost 2009; 7 (1) 132-137
11 Verbruggen B, Meijer P, Novákova I, Van Heerde W. Diagnosis of factor VIII deficiency. Haemophilia 2008; 14 (Suppl 3): 76-82
12 Parquet-Gernez A, Mazurier C, Goudemand M. Functional and immunological assays of FVIII in 133 haemophiliacs--characterization of a subgroup of patients with mild haemophilia A and discrepancy in 1- and 2-stage assays. Thromb Haemost 1988; 59 (2) 202-206
13 Duncan EM, Duncan BM, Tunbridge LJ, Lloyd JV. Familial discrepancy between the one-stage and two-stage factor VIII methods in a subgroup of patients with haemophilia A. Br J Haematol 1994; 87 (4) 846-848
14 Bowyer AE, Van Veen JJ, Goodeve AC, Kitchen S, Makris M. Specific and global coagulation assays in the diagnosis of discrepant mild hemophilia A. Haematologica 2013; 98 (12) 1980-1987
15 Bowyer AE, Goodeve A, Liesner R, Mumford AD, Kitchen S, Makris M. p.Tyr365Cys change in factor VIII: haemophilia A, but not as we know it. Br J Haematol 2011; 154 (5) 618-625
16 Lusher JM, Hillman-Wiseman C, Hurst D. In vivo recovery with products of very high purity--assay discrepancies. Haemophilia 1998; 4 (4) 641-645
17 Morfini M, Cinotti S, Bellatreccia A, Paladino E, Gringeri A, Mannucci PM ; ReFacto-AICE Study Group. A multicenter pharmacokinetic study of the B-domain deleted recombinant factor VIII concentrate using different assays and standards. J Thromb Haemost 2003; 1 (11) 2283-2289
18 Ingerslev J, Jankowski MA, Weston SB, Charles LA ; ReFacto Field Study Participants. Collaborative field study on the utility of a BDD factor VIII concentrate standard in the estimation of BDDr Factor VIII:C activity in hemophilic plasma using one-stage clotting assays. J Thromb Haemost 2004; 2 (4) 623-628
19 Pouplard C, Ternisien C, Desconclois C, Lasne D, Aillaud MF, Caron C. Discrepancies between one stage assay and chromogenic substrate assay in patients treated with recombinant or plasma-derived FVIII and usefulness of a specific standard in ReFacto AF(®) -treated patients. Haemophilia 2016; 22: e101
20 Recht M, Nemes L, Matysiak M , et al. Clinical evaluation of moroctocog alfa (AF-CC), a new generation of B-domain deleted recombinant factor VIII (BDDrFVIII) for treatment of haemophilia A: demonstration of safety, efficacy, and pharmacokinetic equivalence to full-length recombinant factor VIII. Haemophilia 2009; 15 (4) 869-880
21 Kitchen S, Jennings I, Makris M, Kitchen DP, Woods TAL, Walker ID. Factor VIII assay variability in postinfusion samples containing full length and B-domain deleted FVIII. Haemophilia 2016; 22 (5) 806-812
22 Kitchen S, Beckmann H, Katterle Y, Bruns S, Tseneklidou-Stoeter D, Maas Enriquez M. BAY 81-8973, a full-length recombinant factor VIII: results from an international comparative laboratory field study. Haemophilia 2016; 22 (3) e192-e199
23 Hubbard AR, Dodt J, Lee T , et al; Factor VIII and Factor IX Subcommittee of The Scientific and Standardisation Committee of The International Society on Thrombosis and Haemostasis. Recommendations on the potency labelling of factor VIII and factor IX concentrates. J Thromb Haemost 2013; 11 (5) 988-989
24 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
25 Viuff D, Barrowcliffe T, Saugstrup T, Ezban M, Lillicrap D. International comparative field study of N8 evaluating factor VIII assay performance. Haemophilia 2011; 17 (4) 695-702
26 Turecek PL, Romeder-Finger S, Apostol C, Bauer A, Burger D, Hunt A, Gritsch H. A world-wide survey and field study FVIII in clinical hemostasis laboratories to evaluate FVIII:C activity assay variability of ADYNOVATE and OBIZUR in comparison to ADVATE. Haemophilia 2016; 22 (6) 957-965
27 EMA. Joint EMA/EDQM workshop on characterization of new clotting-factor concentrates (factor VIII and factor IX) with respect to potency assays used for labeling and testing of post-infusion samples. Available at: www.ema.europa.eu/docs/en_GB/document_library/Report/2014/07/WC500169760.pdf (Accessed 2014) 2014
28 Pouplard C, Caron C, Kitchen S, Wiken M, Falk Am Ferrante F, Lethagen S. High agreement rate between ellagic acid-based one-stage and chromogenic assays for rFVIIIFc post infusion samples in the A-LONG study. (Abstract) J Thromb Haemost 2016; 14 (Suppl. 01) 58
29 Hillarp A, Bowyer A, Ezban M, Persson P, Kitchen S. Measuring FVIII activity of glycopegylated recombinant FVIII, N8-GP with commercially available one stage clotting assay and chromogenic assay: a two centre study. Haemophilia 2017;
30 Tiefenbacher S, Robinson MM, Ross EL , et al. Comparison of FVIII activity of select novel recombinant FVIII replacement products in commonly used FDA approved one-stage clot assay systems. . (Abstract) J Thromb Haemost 2015; 13 (Suppl. 02) 566
31 Lochu A, Romari N, Beltran J, Magdelaine A, Hermit MB, Ezban M. Influence of FVIII and FIX pegylation on FVIII and FIX activity based APTT assays. . (Abstract) J Thromb Haemost 2013; 11 (Suppl. 02) 970
32 Brand-Staufer BC, Koch K, Balabanov S, Clausen WHO, Exban M. Single center experience evaluating activity of N8-GP with one-stage clotting assay. (Abstract) J Thromb Haemost 2015; 13 (Suppl. 02) 829
33 Doyle MJ, Khan A, DiStasio K, Sullivan A, Triscott M. Accurate recovery of pegylated and non-pegylated therapeutic FVIII, using a specific aPTT reagent, and application on an automated coagulation analyzer. (Abstract) J Thromb Haemost 2015; 13 (Suppl. 02) 295
34 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
35 Gu JM, Ramsey P, Evans V , et al. Evaluation of the activated partial thromboplastin time assay for clinical monitoring of PEGylated recombinant factor VIII (BAY 94-9027) for haemophilia A. Haemophilia 2014; 20 (4) 593-600
36 Rosén P, Rosén 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
37 St. Ledger K, Feussner A, Kalina U. , et al. The FVIII plasma activity of rVIII-SingleChain can be measured in both the one-stage and chromogenic substrate assays. (Abstract) J Thromb Haemost 2015; 13 (Suppl. 02) 540
38 Shojania AM, Tetreault J, Turnbull G. the variations between heparin sensitivity of different lots of activated partial thromboplastin time reagents produced by the same manufacturer. Am J Clin Pathol 1988; 89: 19-23
39 Collins P, Chalmers E, Chowdary P , et al. The use of enhanced half-life coagulation factor concentrates in routine clinical practice: guidance from UKHCDO. Haemophilia 2016; 22 (4) 487-498
40 Pouplard C, Trossaert M, LE Querrec A, Delahousse B, Giraudeau B, Gruel Y. Influence of source of phospholipids for APTT-based factor IX assays and potential consequences for the diagnosis of mild haemophilia B. Haemophilia 2009; 15 (1) 365-368
41 Wilmot HV, Hogwood J, Gray E. Recombinant factor IX: discrepancies between one-stage clotting and chromogenic assays. Haemophilia 2014; 20 (6) 891-897
42 Gritsch H, Romeder-Finger S. Scheiflinger, Turecek PL. Potency assignment and measurement of recombinant FIX activity in human plasma- impact of APTT reagents on the one-stage clotting assay. Haemophilia 2014; 20 (Suppl. 02) 56 (abstract)
43 Bowyer AE, Hillarp A, Ezban M, Persson P, Kitchen S. Measuring factor IX activity of nonacog beta pegol with commercially available one-stage clotting and chromogenic assay kits: a two-center study. J Thromb Haemost 2016; 14 (7) 1428-1435
44 Holm PK, Sorensen MH, Hermit MB, Ezban M. The Activity of GlycoPEGylated Recombinant FIX (N9-GP) can be Measured in Two-Stage Chromogenic and One-Stage Clotting Assays,. 2013 PB 3.49–1, Abstract at XXIV Congress of the International Society on Thrombosis and Haemostasis. Available at: http://www.eventure-online.com/eventure/publicAbstractView.do? id=217022&congressId=6839 . Accessed March 24, 2014
45 Tiefenbacher S, Amiral J, Bowyer A , et al. Qualification of selected one-stage APTT and chromogenic assays for the post-administration monitoring of nonacog beta pegol (Abstract). J Thromb Haemost 2016; 14 (Suppl. 01) 56
46 Robinson MM, Tiefenbacher S, Ross EL , et al. Comparison of FIX activity of select novel recombinant FIX replacement products in commonly used FDA approved one-stage clot assay systems. (Abstract) J Thromb Haemost 2015; 13 (Suppl. 02) 325
47 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
48 Santagostino E, Negrier C, Klamroth R , et al. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. Blood 2012; 120 (12) 2405-2411
49 St Ledger K, Fuessner A, Kalina U, Jacobs I, Voigt C, Bensen-Kennedy D. Performance of a recombinant fusion protein linking coagulation factor IX with albumin (rFIX-FP) in the one –stage assay. Haemophilia 2016; 22 (Suppl. 04) 60 (Abstract)
50 Medical and Scientific Advisory Council (MASAC) of National Hemophilia Foundation. Statement regarding use of various clotting factor assays to monitor factor replacement therapy. Document #228. Available at: http://www.hemophilia.org/sites/default/files/document/files/masac-228.pdf . Accessed September 30, 2016
51 Kitchen S, Blakemore J, Friedman KD , et al. A computer-based model to assess costs associated with the use of factor VIII and factor IX one-stage and chromogenic activity assays. J Thromb Haemost 2016; 14 (4) 757-764