Hamostaseologie 2020; 40(04): 485-490
DOI: 10.1055/a-1223-3353
Review Article

The Art of Detecting Antibodies against Factor VIII

Andreas Tiede
1   Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
,
Lorenzo Alberio
2   Service et Laboratoire Central d'Hématologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
› Author Affiliations

Abstract

Antibodies against factor VIII (FVIII) can be detected based on their ability to neutralize the procoagulant activity of FVIII (neutralizing antibodies, inhibitors), or based on their specific binding capacity to FVIII protein. This article reviews the available assays and their clinical interpretation in patients with congenital and acquired hemophilia.

Zusammenfassung

Antikörper gegen Faktor VIII (FVIII) können anhand ihrer neutralisierenden Funktion gegenüber der prokoagulatorischen FVIII Aktivität oder anhand ihrer Bindung an das FVIII-Protein nachgewiesen werden. Dieser Artikel gibt einen Überblick über die verfügbaren Laborteste und ihre klinische Interpretation bei Patienten mit angeborener oder erworbener Hämophilie.

Disclosures

None.




Publication History

Received: 15 May 2020

Accepted: 20 July 2020

Article published online:
22 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Marder VJ, Mannucci PM, Firkin BG, Hoyer LW, Meyer D. Standard nomenclature for factor VIII and von Willebrand factor: a recommendation by the International Committee on Thrombosis and Haemostasis. Thromb Haemost 1985; 54 (04) 871-872
  • 2 Kasper CK, Aledort L, Aronson D. et al. Proceedings: a more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34 (02) 612
  • 3 Verbruggen B, van Heerde WL, Laros-van Gorkom BA. Improvements in factor VIII inhibitor detection: from Bethesda to Nijmegen. Semin Thromb Hemost 2009; 35 (08) 752-759
  • 4 Verbruggen B, Novakova I, Wessels H, Boezeman J, van den Berg M, Mauser-Bunschoten E. The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: improved specificity and reliability. Thromb Haemost 1995; 73 (02) 247-251
  • 5 Kershaw GW, Chen LS, Jayakodi D, Dunkley SM. Validation of 4% albumin as a diluent in the Bethesda assay for FVIII inhibitors. Thromb Res 2013; 132 (06) 735-741
  • 6 Gawryl MS, Hoyer LW. Inactivation of factor VIII coagulant activity by two different types of human antibodies. Blood 1982; 60 (05) 1103-1109
  • 7 Batty P, Platton S, Bowles L, Pasi KJ, Hart DP. Pre-analytical heat treatment and a FVIII ELISA improve factor VIII antibody detection in acquired haemophilia A. Br J Haematol 2014; 166 (06) 953-956
  • 8 Boylan B, Miller CH. Effects of pre-analytical heat treatment in factor VIII (FVIII) inhibitor assays on FVIII antibody levels. Haemophilia 2018; 24 (03) 487-491
  • 9 Uchida N, Sambe T, Yoneyama K. et al. A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood 2016; 127 (13) 1633-1641
  • 10 Adamkewicz JI, Chen DC, Paz-Priel I. Effects and interferences of emicizumab, a humanised bispecific antibody mimicking activated factor VIII cofactor function, on coagulation assays. Thromb Haemost 2019; 119 (07) 1084-1093
  • 11 Jenkins PV, Bowyer A, Burgess C. et al. Laboratory coagulation tests and emicizumab treatment A United Kingdom Haemophilia Centre Doctors' Organisation guideline. Haemophilia 2020; 26 (01) 151-155
  • 12 Batsuli G, Zimowski KL, Tickle K, Meeks SL, Sidonio Jr RF. Immune tolerance induction in paediatric patients with haemophilia A and inhibitors receiving emicizumab prophylaxis. Haemophilia 2019; 25 (05) 789-796
  • 13 Nogami K, Soeda T, Matsumoto T, Kawabe Y, Kitazawa T, Shima M. Routine measurements of factor VIII activity and inhibitor titer in the presence of emicizumab utilizing anti-idiotype monoclonal antibodies. J Thromb Haemost 2018; 16 (07) 1383-1390
  • 14 Khandelwal A, Phua CW, Chaudhry HR. et al. Confounding effect of therapeutic protamine and heparin levels on routine and special coagulation testing. Blood Coagul Fibrinolysis 2020; 31 (01) 60-64
  • 15 Tripodi A, Mancuso ME, Chantarangkul V. et al. Lupus anticoagulants and their relationship with the inhibitors against coagulation factor VIII: considerations on the differentiation between the 2 circulating anticoagulants. Clin Chem 2005; 51 (10) 1883-1885
  • 16 Miller CH, Rice AS, Boylan B. et al. Hemophilia Inhibitor Research Study Investigators. 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 (07) 1300-1309
  • 17 de Maistre E, Wahl D, Perret-Guillaume C. et al. A chromogenic assay allows reliable measurement of factor VIII levels in the presence of strong lupus anticoagulants. Thromb Haemost 1998; 79 (01) 237-238
  • 18 Payne AB, Miller CH, Ellingsen D, Driggers J, Boylan B, Bean CJ. Reagent substitution in the chromogenic Bethesda assay for factor VIII inhibitors. Haemophilia 2019; 25 (05) e342-e344
  • 19 Türkantoz H, Königs C, Knöbl P. et al. Cross-reacting inhibitors against recombinant porcine factor VIII in acquired hemophilia A: data from the GTH-AH 01/2010 Study. J Thromb Haemost 2020; 18 (01) 36-43
  • 20 Abou-Ismail MY, Vuyyala S, Prunty J, Schmaier AH, Nayak L. Short term efficacy of recombinant porcine factor VIII in patients with factor VIII inhibitors. Haemophilia 2020
  • 21 Bonar RA, Favaloro EJ, Marsden K. External quality assessment of factor VIII inhibitor assays. Semin Thromb Hemost 2013; 39 (03) 320-326
  • 22 Werwitzke S, Geisen U, Nowak-Göttl U. et al. Diagnostic and prognostic value of factor VIII binding antibodies in acquired hemophilia A: data from the GTH-AH 01/2010 study. J Thromb Haemost 2016; 14 (05) 940-947
  • 23 Whelan SF, Hofbauer CJ, Horling FM. et al. Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients. Blood 2013; 121 (06) 1039-1048
  • 24 Tiede A, Hofbauer CJ, Werwitzke S. et al. Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. Blood 2016; 127 (19) 2289-2297
  • 25 Kahle J, Orlowski A, Stichel D. et al. Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in acquired and congenital hemophilia A. Blood 2017; 130 (06) 808-816
  • 26 Hofbauer CJ, Whelan SF, Hirschler M. et al. Affinity of FVIII-specific antibodies reveals major differences between neutralizing and nonneutralizing antibodies in humans. Blood 2015; 125 (07) 1180-1188
  • 27 Hofbauer CJ, Kepa S, Schemper M. et al. FVIII-binding IgG modulates FVIII half-life in patients with severe and moderate hemophilia A without inhibitors. Blood 2016; 128 (02) 293-296
  • 28 Montalvão SA, Tucunduva AC, Siqueira LH, Sambo AL, Medina SS, Ozelo MC. A longitudinal evaluation of anti-FVIII antibodies demonstrated IgG4 subclass is mainly correlated with high-titre inhibitor in haemophilia A patients. Haemophilia 2015; 21 (05) 686-692