A critical appraisal of one-stage and chromogenic assays of factor VIII activity

Journal of Thrombosis and Haemostasis

Volumn 14, Issue 2, 2016, Pages 248-261

  Peyvandi, Flora ^a   Oldenburg, J ^b   Friedman, K D ^c  

^a UNIVERSITY OF MILAN   (Italy)

^b UNIVERSITY HOSPITAL BONN   (Germany)

^c BLOOD RESEARCH INSTITUTE   (United States)

Author keywords

Activated partial thromboplastin time; Assay; Blood coagulation tests; Factor VIII; Hemophilia A

Indexed keywords

BLOOD CLOTTING FACTOR 8; MACROGOL; RECOMBINANT BLOOD CLOTTING FACTOR 8; BIOLOGICAL MARKER; CHROMOGENIC SUBSTRATE; DIAGNOSTIC KIT; F8 PROTEIN, HUMAN; HEMOSTATIC AGENT;

ARTICLE; CHROMOGENIC FACTOR XIII ASSAY; CHROMOGENIC SUBSTRATE ASSAY; DISEASE SEVERITY; EUROPE; HEMOPHILIA A; HUMAN; INTERMETHOD COMPARISON; MONITORING; ONE STAGE CLOTTING ASSAY; PARTIAL THROMBOPLASTIN TIME; PRIORITY JOURNAL; PROTEIN MODIFICATION; STANDARD; UNITED STATES; BLOOD; BLOOD CLOTTING; BLOOD CLOTTING TEST; DIAGNOSTIC KIT; DRUG EFFECTS; DRUG MONITORING; OBSERVER VARIATION; PREDICTIVE VALUE; PROCEDURES; QUALITY CONTROL; REPRODUCIBILITY; STANDARDS;

BIOMARKERS; BLOOD COAGULATION; BLOOD COAGULATION TESTS; CHROMOGENIC COMPOUNDS; DRUG MONITORING; FACTOR VIII; HEMOPHILIA A; HEMOSTATICS; HUMANS; OBSERVER VARIATION; PREDICTIVE VALUE OF TESTS; QUALITY CONTROL; REAGENT KITS, DIAGNOSTIC; REPRODUCIBILITY OF RESULTS;

EID: 84976209150     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/jth.13215     Document Type: Article

References (78)

1. Fay PJ. Factor VIII structure and function. Int J Hematol 2006; 83: 103-8.
2. Lenting PJ, van Mourik JA, Mertens K. The life cycle of coagulation factor VIII in view of its structure and function. Blood 1998; 92: 3983-96.
3. Vehar GA, Keyt B, Eaton D, Rodriguez H, O'Brien DP, Rotblat F, Oppermann H, Keck R, Wood WI, Harkins RN, Tuddenham EG, Lawn RM, Capon DJ. Structure of human factor VIII. Nature 1984; 312: 337-42.
4. Andersson LO, Forsman N, Huang K, Larsen K, Lundin A, Pavlu B, Sandberg H, Sewerin K, Smart J. Isolation and characterization of human factor VIII: molecular forms in commercial factor VIII concentrate, cryoprecipitate, and plasma. Proc Natl Acad Sci USA 1986; 83: 2979-83.
5. Fay PJ, Anderson MT, Chavin SI, Marder VJ. The size of human factor VIII heterodimers and the effects produced by thrombin. Biochim Biophys Acta 1986; 871: 268-78.
6. Eaton D, Rodriguez H, Vehar GA. Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity. Biochemistry 1986; 25: 505-12.
7. Fang H, Wang L, Wang H. The protein structure and effect of factor VIII. Thromb Res 2007; 119: 1-13.
8. 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: 637-47.
9. Over J. Methodology of the one-stage assay of factor VIII (VIII:C). Scand J Haematol Suppl 1984; 41: 13-24.
10. Barrowcliffe TW. Laboratory testing and standardisation. Haemophilia 2013; 19: 799-804.
11. Potgieter JJ, Damgaard M, Hillarp A. One-stage vs. chromogenic assays in haemophilia A. Eur J Haematol 2015; 94(Suppl. 77): 38-44.
12. Aurell L, Friberger P, Karlsson G, Claeson G. A new sensitive and highly specific chromogenic peptide substrate for factor Xa. Thromb Res 1977; 11: 595-609.
13. Svendsen L, Blombäck B, Blombäck M, Olsson PI. Synthetic chromogenic substrates for determination of trypsin, thrombin and thrombin-like enzymes. Thromb Res 1972; 1: 267-78.
14. Rosen S. Assay of factor VIII:C with a chromogenic substrate. Scand J Haematol Suppl 1984; 40: 139-45.
15. Carlebjork G, Blomback M, Blomstedt M, Akerblom O. Screening of factor VIII:C levels in blood donors. Vox Sang 1986; 51: 306-9.
16. Rosen S. Chromogenic methods in coagulation diagnostics. Hamostaseologie 2005; 25: 259-66.
17. Barrowcliffe TW. Standardization of FVIII & FIX assays. Haemophilia 2003; 9: 397-402.
18. Mani H, Lindhoff-Last E. Main considerable factors for correct laboratory test interpretation under DOA treatment. Thromb J 2013; 11: 22-26.
19. Lippi G, Franchini M, Favaloro EJ. One-stage clotting versus chromogenic assays for assessing recombinant factor VIII: two faces of a haemostasis coin. Blood Coagul Fibrinolysis 2009; 20: 1-3.
20. Oldenburg J, Pavlova A. Discrepancy between one-stage and chromogenic factor VIII activity assay results can lead to misdiagnosis of haemophilia A phenotype. Hamostaseologie 2010; 30: 207-11.
21. Pavlova A, Delev D, Pezeshkpoor B, Muller J, Oldenburg J. Haemophilia A mutations in patients with non-severe phenotype associated with a discrepancy between one-stage and chromogenic factor VIII activity assays. Thromb Haemost 2014; 111: 851-61.
22. Miller CH, Rice AS, Boylan B, Shapiro AD, Lentz SR, Wicklund BM, Kelly FM, Soucie JM. Comparison of clot-based, chromogenic and fluorescence assays for measurement of factor VIII inhibitors in the US Hemophilia Inhibitor Research Study. J Thromb Haemost 2013; 11: 1300-9.
23. Hubbard AR, Dodt J, Lee T, Mertens K, Seitz R, Srivastava A, Weinstein M. Recommendations on the potency labelling of factor VIII and factor IX concentrates. J Thromb Haemost 2013; 11: 988-9.
24. European Medicines Agency. Workshop report: characterisation of new clotting factor concentrates (FVIII, FIX) with respect to potency assays used for labelling and testing of post infusion samples. http://www.ema.europa.eu/docs/en_GB/document_library/Report/2014/07/WC500169760.pdf.2014. Accessed 23 September 2014.
25. Hubbard AR, Sands D, Sandberg E, Seitz R, Barrowcliffe TW. A multi-centre collaborative study on the potency estimation of ReFacto. Thromb Haemost 2003; 90: 1088-93.
26. Lollar P. The factor VIII assay problem: neither rhyme nor reason. J Thromb Haemost 2003; 1: 2275-9.
27. Gruppo RA, Brown D, Wilkes MM, Navickis RJ. Increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII - a robust meta-analytic finding. Haemophilia 2004; 10: 449-51.
28. Gruppo RA, Brown D, Wilkes MM, Navickis RJ. Meta-analytic evidence of increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII. Haemophilia 2004; 10: 747-50.
29. Pollmann H, Externest D, Ganser A, Eifrig B, Kreuz W, Lenk H, Pabinger I, Schramm W, Schwarz TF, Zimmermann R, Zavazava N, Oldenburg J, Klamroth R. Efficacy, safety and tolerability of recombinant factor VIII (REFACTO) in patients with haemophilia A: interim data from a postmarketing surveillance study in Germany and Austria. Haemophilia 2007; 13: 131-43.
30. Barrowcliffe TW, Hubbard AR, Kitchen S. Standards and monitoring treatment. Haemophilia 2012; 18(Suppl. 4): 61-5.
31. Barrowcliffe TW. Factor VIII and factor IX Sub-Committee. Recommendations for the assay of high-purity factor VIII concentrates. Thromb Haemost 1993; 70: 876-7.
32. Barrowcliffe TW, Mertens K, Preston FE, Ingerslev J. Laboratory aspects of haemophilia therapy. Haemophilia 2002; 8: 244-9.
33. Raut S, Sands D, Heath AB, Barrowcliffe TW. Variability in factor VIII concentrate measurement: results from SSC field collaborative studies. J Thromb Haemost 2003; 1: 1927-34.
34. Barrowcliffe TW, Raut S, Sands D, Hubbard AR. Coagulation and chromogenic assays of factor VIII activity: general aspects, standardization, and recommendations. Semin Thromb Hemost 2002; 28: 247-56.
35. Ingerslev J, Jankowski MA, Weston SB, Charles LA. 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: 623-8.
36. Mikaelsson M, Oswaldsson U, Sandberg H. Influence of phospholipids on the assessment of factor VIII activity. Haemophilia 1998; 4: 646-50.
37. Pahl S, Pavlova A, Driesen J, Muller J, Potzsch B, Oldenburg J. In vitro characterization of recombinant factor VIII concentrates reveals significant differences in protein content, activity and thrombin activation profile. Haemophilia 2013; 19: 392-8.
38. Hubbard AR, Weller LJ, Bevan SA. A survey of one-stage and chromogenic potencies in therapeutic factor VIII concentrates. Br J Haematol 2002; 117: 247-8.
39. 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.
40. Gouws W, Botha E, Visser A. Method validation and clinical utility of chromogenic factor VIII assay compared to one-stage assay. J Thromb Thrombolysis 2014; 37: 210-15.
41. Viuff D, Barrowcliffe T, Saugstrup T, Ezban M, Lillicrap D. International comparative field study of N8 evaluating factor VIII assay performance. Haemophilia 2011; 17: 695-702.
42. Sommer JM, Moore N, McGuffie-Valentine B, Bardan S, Buyue Y, Kamphaus GD, Konkle BA, Pierce GF. Comparative field study evaluating the activity of recombinant factor VIII Fc fusion protein in plasma samples at clinical haemostasis laboratories. Haemophilia 2014; 20: 294-300.
43. Chandler WL, Ferrell C, Lee J, Tun T, Kha H. Comparison of three methods for measuring factor VIII levels in plasma. Am J Clin Pathol 2003; 120: 34-9.
44. Bowyer AE, van Veen JJ, Goodeve A, Kitchen S, Makris M. Specific and global coagulation assays in the diagnosis of discrepant mild hemophilia A. Haematologica 2013; 98: 1980-7.
45. Pahl S, Schwaab R, Oldenburg J, Herbiniaux U, Aburubaiha Z. Characterisation of natural FVIII variants of the B-domain regarding their biological activity. Haemophilia 2010; 16 (Suppl. 4): 95. Abstract number is 21P19.
46. Krogh-Meibom T, Olsen E, Kjalke M, Ezban M. The activity of glycoPEGylated recombinant FVIII (N8-GP) can be measured in both two-stage chromogenic and one-stage clotting assays. J Thromb Haemost 2013; 11(Suppl. s2): 1042 (PO 059).
47. Lochu A, Romari N, Beltran J, Magdelaine A, Ezban M, Brunsgaard HM. Influence of FIX and FVIII PEGYLATION on FIX and FVIII activity based on APTT assays. J Thromb Haemost 2013; 11(Suppl. s2): 970 (PB 4.54-1).
48. 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: 846-8.
49. Mazurier C, Gaucher C, Jorieux S, Parquet-Gernez A. Mutations in the FVIII gene in seven families with mild haemophilia A. Br J Haematol 1997; 96: 426-7.
50. 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: 202-6.
51. Rudzki Z, Duncan EM, Casey GJ, Neumann M, Favaloro EJ, Lloyd JV. Mutations in a subgroup of patients with mild haemophilia A and a familial discrepancy between the one-stage and two-stage factor VIII:C methods. Br J Haematol 1996; 94: 400-6.
52. Schwaab R, Oldenburg J, Kemball-Cook G, Albert T, Juhler C, Hanfland P, Ingerslev J. Assay discrepancy in mild haemophilia A due to a factor VIII missense mutation (Asn694Ile) in a large Danish family. Br J Haematol 2000; 109: 523-8.
53. Poulsen AL, Pedersen LH, Hvas AM, Poulsen LH, Thykjaer H, Ingerslev J. Assay discrepancy in mild haemophilia A: entire population study in a National Haemophilia Centre. Haemophilia 2009; 15: 285-9.
54. Pipe SW, Saenko EL, Eickhorst AN, Kemball-Cook G, Kaufman RJ. Hemophilia A mutations associated with 1-stage/2-stage activity discrepancy disrupt protein-protein interactions within the triplicated A domains of thrombin-activated factor VIIIa. Blood 2001; 97: 685-91.
55. Cid AR, Calabuig M, Cortina V, Casana P, Haya S, Moret A, Cabrera N, Aznar JA. One-stage and chromogenic FVIII:C assay discrepancy in mild haemophilia A and the relationship with the mutation and bleeding phenotype. Haemophilia 2008; 14: 1049-54.
56. Keeling DM, Sukhu K, Kemball-Cook G, Waseem N, Bagnall R, Lloyd JV. Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His 1954→Leu substitution in the factor VIII A3 domain. Br J Haematol 1999; 105: 1123-6.
57. Rodgers SE, Duncan EM, Sobieraj-Teague M, Lloyd JV. Evaluation of three automated chromogenic FVIII kits for the diagnosis of mild discrepant haemophilia A. Int J Lab Hematol 2009; 31: 180-8.
58. Mumford AD, Laffan M, O'Donnell J, McVey JH, Johnson DJ, Manning RA, Kemball-Cook G. A Tyr346→Cys substitution in the interdomain acidic region a1 of factor VIII in an individual with factor VIII:C assay discrepancy. Br J Haematol 2002; 118: 589-94.
59. Lyall H, Hill M, Westby J, Grimley C, Dolan G. Tyr346→Cys mutation results in factor VIII:C assay discrepancy and a normal bleeding phenotype - is this mild haemophilia A? Haemophilia 2008; 14: 78-80.
60. Celie PH, van Stempvoort G, Jorieux S, Mazurier C, van Mourik JA, Mertens K. Substitution of Arg527 and Arg531 in factor VIII associated with mild haemophilia A: characterization in terms of subunit interaction and cofactor function. Br J Haematol 1999; 106: 792-800.
61. Kitchen S, Hayward C, Negrier C, Dargaud Y. New developments in laboratory diagnosis and monitoring. Haemophilia 2010; 16(Suppl. 5): 61-6.
62. Trossaert M, Lienhart A, Nougier C, Fretigny M, Sigaud M, Meunier S, Fouassier M, Ternisien C, Negrier C, Dargaud Y. Diagnosis and management challenges in patients with mild haemophilia A and discrepant FVIII measurements. Haemophilia 2014; 20: 550-8.
63. 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: 618-25.
64. Duncan EM, Rodgers SE, McRae SJ. Diagnostic testing for mild hemophilia A in patients with discrepant one-stage, two-stage, and chromogenic factor VIII:C assays. Semin Thromb Hemost 2013; 39: 272-82.
65. Makris M, Peyvandi F. Assaying FVIII activity: one method is not enough, and never was. Haemophilia 2014; 20: 301-3.
66. Kitchen S, Gray E, Mertens K. Monitoring of modified factor VIII and IX products. Haemophilia 2014; 20(Suppl. 4): 36-42.
67. Lee C, Barrowcliffe T, Bray G, Gomperts E, Hubbard A, Kemball-Cook G, Lilley P, Owens D, von Tilberg L, Pasi J. Pharmacokinetic in vivo comparison using 1-stage and chromogenic substrate assays with two formulations of Hemofil-M. Thromb Haemost 1996; 76: 950-6.
68. Tiede A, Ezban M, Krogh-Meibom T, Saugstrup T, Møss J. Factor VIII assessment using one-stage clot and chromogenic assay in trials investigating pharmacokinetics of different FVIII products. J Thromb Haemost 2013; 11(Suppl. s2): 974 (PB 4.55-5).
69. Pabinger I, Klamroth R, Valentino R, Gill J, Levy H, Samuels R, Parasrampuria R. Pharmacokinetic results from a phase I/III study of a novel recombinant single-chain factor VIII (rVIII-SingleChain) compared to octocog alfa in severe haemophilia A patients. J Thromb Haemost 2013; 11(Suppl. s2): 712 (PB 2.55-4).
70. Gu JM, Ramsey P, Evans V, Tang L, Apeler H, Leong L, Murphy JE, Laux V, Myles T. 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: 593-600.
71. Turecek P, Weber A, Engelmaier A, Mohr G, Schwarz HP, Scheiflinger F. Modification-dependent activity assay: a new assay type for selective activity measurement of PEGylated human factor VIII (BAX 855). J Thromb Haemost 2013; 11(Suppl. s2): 1043 (PO 061).
72. Stennicke HR, Kjalke M, Karpf DM, Balling KW, Johansen PB, Elm T, Ovlisen K, Moller F, Holmberg HL, Gudme CN, Persson E, Hilden I, Pelzer H, Rahbek-Nielsen H, Jespersgaard C, Bogsnes A, Pedersen AA, Kristensen AK, Peschke B, Kappers W, et al. A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models. Blood 2013; 121: 2108-16.
73. Morfini M, Cinotti S, Bellatreccia A, Paladino E, Gringeri A, Mannucci PM. A multicenter pharmacokinetic study of the B-domain deleted recombinant factor VIII concentrate using different assays and standards. J Thromb Haemost 2003; 1: 2283-9.
74. Pouplard C, Caron C, Aillaud MF, Ternisien C, Desconclois C, Dubanchet A, Sobas F. The use of the new ReFacto AF Laboratory Standard allows reliable measurement of FVIII:C levels in ReFacto AF mock plasma samples by a one-stage clotting assay. Haemophilia 2011; 17: e958-62.
75. Klukowska A, Vdovin V, Szczepanski T, Jansen M, Knaub S, Liesner R. Clinical study in children with severe haemophilia A investigating efficacy, immunogenicity, pharmacokinetics, and safety of human-cl rhFVIII. J Thromb Haemost 2013; 11(Suppl. s2): 532 (PB 1.36-5).
76. Knaub S, Tiede A, Lissitchkov T, Valentino LA, Powell JS, Manco-Johnson MJ. A prospective, multi-center, randomized clinical trial to compare the pharmacokinetic properties of human-Cl rhFVIII, a new human-cell line derived recombinant factor VIII, with those of a full-length recombinant factor VIII expressed in baby hamster kidney cells. Blood (ASH Annual Meeting Abstracts) 2011; 118: 3309.
77. Sandberg H, Kannicht C, Stenlund P, Dadaian M, Oswaldsson U, Cordula C, Walter O. Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII. Thromb Res 2012; 130: 808-17.
78. Powell JS, Josephson NC, Quon D, Ragni MV, Cheng G, Li E, Jiang H, Li L, Dumont JA, Goyal J, Zhang X, Sommer J, McCue J, Barbetti M, Luk A, Pierce GF. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood 2012; 119: 3031-7.