Measuring factor IX activity of nonacog beta pegol with commercially available one-stage clotting and chromogenic assay kits: a two-center study

Journal of Thrombosis and Haemostasis

Volumn 14, Issue 7, 2016, Pages 1428-1435

  Bowyer, A E ^a   Hillarp, A ^b   Ezban, M ^c   Persson, P ^c   Kitchen, S ^a  

^a SHEFFIELD TEACHING HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^b LUND UNIVERSITY HOSPITAL   (Sweden)

^c NOVO NORDISK A S   (Denmark)

Author keywords

blood coagulation test; factor IX; hemophilia B; nonacog beta pegol; poly(ethylene glycol)

Indexed keywords

BLOOD CLOTTING FACTOR 9; BLOOD CLOTTING FACTOR 9 CONCENTRATE; RECOMBINANT BLOOD CLOTTING FACTOR 9;

ANALYZER; ARTICLE; BLOOD CLOTTING; BLOOD CLOTTING TEST; CHROMOGENIC ASSAY; CONTROLLED STUDY; HEMATOLOGY TEST KIT; HEMOPHILIA B; LABORATORY; MEASUREMENT ACCURACY; ONE STAGE CLOTTING ASSAY; PARTIAL THROMBOPLASTIN TIME; PRIORITY JOURNAL;

EID: 84990198558     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.13348     Document Type: Article

References (26)

1. Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A; Treatment Guidelines Working Group on Behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophilia 2013; 19: e1–47.
2. Ostergaard H, Bjelke JR, Hansen L, Petersen LC, Pedersen AA, Elm T, Moller F, Hermit MB, Holm PK, Krogh TN, Petersen JM, Ezban M, Sorensen BB, Andersen MD, Agerso H, Ahmadian H, Balling KW, Christiansen ML, Knobe K, Nichols TC, et al. Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide. Blood 2011; 118: 2333–41.
3. Sommer JM, Buyue Y, Bardan S, Peters RT, Jiang H, Kamphaus GD, Gray E, Pierce GF. Comparative field study: impact of laboratory assay variability on the assessment of recombinant factor IX Fc fusion protein (rFIXFc) activity. Thromb Haemost 2014; 112: 932–40.
4. Stennicke HR, Ostergaard H, Bayer RJ, Kalo MS, Kinealy K, Holm PK, Sorensen BB, Zopf D, Bjorn SE. Generation and biochemical characterization of glycoPEGylated factor VIIa derivatives. Thromb Haemost 2008; 100: 920–8.
5. Collins PW, Young G, Knobe K, Karim FA, Angchaisuksiri P, Banner C, Gursel T, Mahlangu J, Matsushita T, Mauser-Bunschoten EP, Oldenburg J, Walsh CE, Negrier C; Paradigm 2 Investigators. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood 2014; 124: 3880–6.
6. Collins PW, Moss J, Knobe K, Groth A, Colberg T, Watson E. Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. J Thromb Haemost 2012; 10: 2305–12.
7. Kitchen S, Signer-Romero K, Key NS. Current laboratory practices in the diagnosis and management of haemophilia: a global assessment. Haemophilia 2015; 21: 550–7.
8. Kitchen S, Gray E, Mertens K. Monitoring of modified factor VIII and IX products. Haemophilia 2014; 20(Suppl. 4): 36–42.
9. Hubbard AR, Dodt J, Lee T, Mertens K, Seitz R, Srivastava A, Weinstein M. Factor VII, Factor IXSoTS, 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: 988–9.
10. Bowyer A, Hillarp A, Persson M, Ezban M, Persson P, Kitchen S. The laboratory measurement of a glycopegylated recombinant FIX, N9-GP: a two centre study. J Thromb Haemost 2014; 12(Suppl. 1): 32–33 (abstract EHF11).
11. Holm PK, Sørensen MH, Hermit BM, Ezban M. The activity of GlycoPEGylated recombinant FIX (N9-GP) can be measured in two-stage chromogenic and one-stage clotting assays. J Thromb Haemost 2013; 11(Suppl. 2): 828 (abstract PB 3.49-1).
12. Hermit MB, Sorensen MH, Ezban M, Lochu A, Magdelaine A. Pegylation of FIX influences the clotting time in APTT assays. Use of product specific standard eliminates PEG interference. Haemophilia 2013; 19: 45 (abstract PO059).
13. Lochu A, Romari N, Beltran J, Magdelaine A, Ezban M, Hermit MB. Influence of FIX and FVIII PEGYLATION on FIX and FVIII activity based on APTT assays. J Thromb Haemost 2014; 11(Suppl. 2): 970 (abstract PB 4.54-1).
14. 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: 365–8.
15. Gritsch H, Romeda-Finger S, Scheiflinger F, Turecek PL. Potency assignment and measurement of recombinant FIX activity in human plasma – impact of aPTT reagents on the 1-stage clotting assay. Haemophilia 2014; 20(Suppl. 3): 37 (abstract).
16. Wilmot HV, Hogwood J, Gray E. Recombinant factor IX: discrepancies between one-stage clotting and chromogenic assays. Haemophilia 2014; 20: 891–7.
17. MASAC statement regarding use of various clotting factor assays to monitor factor replacement therapy. National Hemophilia Foundation MASAC Document #228. 2014. http://www.hemophilia.org/sites/default/files/document/files/masac-228.pdf. Accessed 16 March 2015.
18. Mikaelsson M, Oswaldsson U, Sandberg H. Influence of phospholipids on the assessment of factor VIII activity. Haemophilia 1998; 4: 646–50.
19. Caron C, Dautzenberg MD, Delahousse B, Droulle C, Pouzol P, Dubanchet A, Rothschild C. A blinded in vitro study with Refacto mock plasma samples: similar FVIII results between the chromogenic assay and a one-stage assay when using a higher cephalin dilution. Haemophilia 2002; 8: 639–43.
20. Mikaelsson M, Oswaldsson U. Assaying the circulating factor VIII activity in hemophilia A patients treated with recombinant factor VIII products. Semin Thromb Hemost 2002; 28: 257–64.
21. Lusher JM, Hillman-Wiseman C, Hurst D. In vivo recovery with products of very high purity – assay discrepancies. Haemophilia 1998; 4: 641–5.
22. Rosén P, Rosén S, Ezban M, Persson E. N9-GP overestimation in one-stage clot method due to silica-mediated conversion to fixa during contact activation. J Thromb Haemost 2015; 13: 315.
23. Kitchen S, Cartwright I, Woods TA, Jennings I, Preston FE. Lipid composition of seven APTT reagents in relation to heparin sensitivity. Br J Haematol 1999; 106: 801–8.
24. Barrowcliffe TW, Hubbard AR, Kitchen S. Standards and monitoring treatment. Haemophilia 2012; 18(Suppl. 4): 61–5.
25. Dodt J, Hubbard AR, Wicks SJ, Gray E, Neugebauer B, Charton E, Silvester G. Potency determination of factor VIII and factor IX for new product labelling and postinfusion testing: challenges for caregivers and regulators. Haemophilia 2015; 21: 543–9.
26. Sørensen MH, Andersen S, Ezban M. Factor IX-deficient plasma spiked with N9-GP behaves similarly to N9-GP post-administration clinical samples in N9-GP ELISA and FIX activity assays. Haemophilia 2015; 21: 832–6.