A modified thrombin generation assay to evaluate the plasma coagulation potential in the presence of emicizumab, the bispecific antibody to factors IXa/X.
Antibodies, Bispecific
/ pharmacology
Antibodies, Monoclonal, Humanized
/ pharmacology
Blood Coagulation Tests
/ methods
Dose-Response Relationship, Drug
Drug Synergism
Drug Therapy, Combination
Factor VIII
/ pharmacology
Factor X
/ immunology
Hemophilia A
/ blood
Hemorrhage
/ etiology
Humans
Partial Thromboplastin Time
Thrombin
/ metabolism
Bispecific antibodies
Blood coagulation tests
Factor VIII
Hemophilia A
Treatment
Journal
International journal of hematology
ISSN: 1865-3774
Titre abrégé: Int J Hematol
Pays: Japan
ID NLM: 9111627
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
03
04
2020
accepted:
21
07
2020
revised:
18
06
2020
pubmed:
5
8
2020
medline:
25
11
2020
entrez:
5
8
2020
Statut:
ppublish
Résumé
Emicizumab shortens activated partial thromboplastin time (aPTT) greater than Factor (F)VIII. Clot waveform analysis triggered by ellagic acid and tissue factor trigger (Elg/TF) provided a useful means of assessing emicizumab activity. Thrombin generation assays (TGA) using this trigger reagent might also overcome the difficulties associated with aPTT by emicizumab. To compare TGA triggered by Elg/TF and other reagents (FXIa, TF) for evaluating emicizumab activity. Emicizumab, FVIII, or FVIII-bypassing agents (BPAs) were incubated with FVIII-deficient plasmas prior to TGA initiated by Elg/TF (0.2 μM/0.5 pM), FXIa (5.21 pM), or TF (PPP-Reagent LOW
Identifiants
pubmed: 32748217
doi: 10.1007/s12185-020-02959-x
pii: 10.1007/s12185-020-02959-x
doi:
Substances chimiques
Antibodies, Bispecific
0
Antibodies, Monoclonal, Humanized
0
emicizumab
7NL2E3F6K3
Factor VIII
9001-27-8
Factor X
9001-29-0
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
621-630Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 18K07885
Références
Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357:535–44.
doi: 10.1056/NEJMoa067659
De Moerloose P, Urbancik W, Van Den Berg HM, Richards M. A survey of adherence to haemophilia therapy in six European countries: results and recommendations. Haemophilia. 2008;14:931–8.
doi: 10.1111/j.1365-2516.2008.01843.x
Beeton K, Neal D, Watson T, Lee CA. Parents of children with haemophilia—a transforming experience. Haemophilia. 2007;13:570–9.
doi: 10.1111/j.1365-2516.2007.01494.x
Walsh CE, Jiménez-Yuste V, Auerswald G, Grancha S. The burden of inhibitors in haemophilia patients. Thromb Haemost. 2016;116(Suppl. 1):S10–7.
doi: 10.1160/TH16-01-0049
Gouw SC, van den Berg HM, Fischer K, Auerswald G, Carcao M, Chalmers E, et al. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood. 2013;121:4046–55.
doi: 10.1182/blood-2012-09-457036
Sampei Z, Igawa T, Soeda T, Okuyama-Nishida Y, Moriyama C, Wakabayashi T, et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS ONE. 2013;8:e57479.
doi: 10.1371/journal.pone.0057479
Kitazawa T, Igawa T, Sampei Z, Muto A, Kojima T, Soeda T, et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med. 2012;18:1570–4.
doi: 10.1038/nm.2942
Uchida N, Sambe T, Yoneyama K, Fukazawa N, Kawanishi T, Kobayashi S, et al. A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood. 2016;127:1633–41.
doi: 10.1182/blood-2015-06-650226
Shima M, Nogami K, Nagami S, Yoshida S, Yoneyama K, Ishiguro A, et al. A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors. Haemophilia. 2019;25:979–87.
doi: 10.1111/hae.13848
Pipe SW, Shima M, Lehle M, Shapiro A, Chebon S, Fukutake K, et al. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. Lancet Haematol. 2019;6:e295–305.
doi: 10.1016/S2352-3026(19)30054-7
Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379:811–22.
doi: 10.1056/NEJMoa1803550
Young G, Liesner R, Sidonio RF Jr, Oldenburg J, Jimenez-Yuste V, Mahlangu J, et al. Emicizumab prophylaxis provides flexible and effective bleed control in children with hemophilia Α with inhibitors: results from the HAVEN 2 Study. Blood. 2018;132:632.
doi: 10.1182/blood-2018-99-118153
Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377:809–18.
doi: 10.1056/NEJMoa1703068
Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, et al. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors. Blood Adv. 2017;1:1891–9.
doi: 10.1182/bloodadvances.2017006684
Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med. 2016;374:2044–53.
doi: 10.1056/NEJMoa1511769
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;16:1383–90.
doi: 10.1111/jth.14135
Nogami K, Matsumoto T, Tabuchi Y, Soeda T, Arai N, Kitazawa T, et al. Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab. J Thromb Haemost. 2018;16:1078–88.
doi: 10.1111/jth.14022
Hemker HC, Giesen P, AlDieri R, Regnault V, de Smed E, Wagenvoord R, et al. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb. 2002;32:249–53.
doi: 10.1159/000073575
Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev. 2003;17(Suppl 1):S1–5.
doi: 10.1016/S0268-960X(03)90000-2
Barg AA, Avishai E, Budnik I, Levy-Mendelovich S, Barazani TB, Kenet G, et al. Emicizumab prophylaxis among infants and toddlers with severe hemophilia A and inhibitors-a single-center cohort. Pediatr Blood Cancer. 2019;66:e27886.
doi: 10.1002/pbc.27886
Kizilocak H, Yukhtman CL, Marquez-Casas E, Lee J, Donkin J, Young G. Management of perioperative hemostasis in a severe hemophilia A patient with inhibitors on emicizumab using global hemostasis assays. Ther Adv Hematol. 2019;10:2040620719860025.
doi: 10.1177/2040620719860025
Dargaud Y, Lienhart A, Janbain M, Le Quellec S, Enjolras N, Negrier C. Use of thrombin generation assay to personalize treatment of breakthrough bleeds in a patient with hemophilia and inhibitors receiving prophylaxis with emicizumab. Haematologica. 2018;103:e181–3.
doi: 10.3324/haematol.2017.185330
Matsumoto T, Nogami K, Ogiwara K, Shima M. A modified thrombin generation test for investigating very low levels of factor VIII activity in hemophilia A. Int J Hematol. 2009;90:576–82.
doi: 10.1007/s12185-009-0450-y
Kumano O, Ieko M, Naito S, Yoshida M, Takahashi N. APTT reagent with ellagic acid as activator shows adequate lupus anticoagulant sensitivity in comparison to silica-based reagent. J Thromb Haemost. 2012;10:2338–43.
doi: 10.1111/j.1538-7836.2012.04906.x
Okuda M, Yamamoto Y. Usefulness of synthetic phospholipid in measurement of activated partial thromboplastin time: a new preparation procedure to reduce batch difference. Clin Lab Haematol. 2004;26:215–23.
doi: 10.1111/j.1365-2257.2004.00605.x
Mimms LT, Zampighi G, Nozaki Y, Tanford C, Reynolds JA. Phospholipid vesicle formation and transmembrane protein incorporation using octyl glucoside. Biochemistry. 1981;20:833–40.
doi: 10.1021/bi00507a028
Muto A, Yoshihashi K, Takeda M, Kitazawa T, Soeda T, Igawa T, et al. Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation. J Thromb Haemost. 2014;12:206–13.
doi: 10.1111/jth.12474
Yada K, Nogami K, Ogiwara K, Shida Y, Furukawa S, Yaoi H, et al. Global coagulation function assessed by rotational thromboelastometry predicts coagulation-steady state in individual hemophilia A patients receiving emicizumab prophylaxis. Int J Hematol. 2019;110:419–30.
doi: 10.1007/s12185-019-02698-8
Yada K, Nogami K, Kitazawa T, Hattori K, Shima M. Mode of enhancement in the global hemostatic potentials with concomitant use of bypassing agents and emicizumab in hemophilia A patients with inhibitor evaluated by ROTEM. Res Pract Thromb Haemost. 2017;1(Suppl. 1):163–4.
Matsumoto T, Shima M, Takeyama M, Yoshida K, Tanaka I, Sakurai Y, et al. The measurement of low levels of factor VIII or factor IX in hemophilia A and hemophilia B plasma by clot waveform analysis and thrombin generation assay. J Thromb Haemost. 2006;4:377–84.
doi: 10.1111/j.1538-7836.2006.01730.x
Yu Y, Millar CM. Measurement of factor IX activity in plasma-derived and recombinant concentrates: insights from thrombin generation and activation-based assays. J Thromb Haemost. 2014;12:62–70.
doi: 10.1111/jth.12452
Dargaud Y, Wolberg AS, Gray E, Negrier C, Hemker HC. Proposal for standardized preanalytical and analytical conditions for measuring thrombin generation in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2017;15:1704–7.
doi: 10.1111/jth.13743
Viuff D, Andersen S, Sorensen BB, Lethagen S. Optimizing thrombelastography (TEG) assay conditions to monitor rFVIIa (NovoSeven) therapy in haemophilia A patients. Thromb Res. 2010;126:144–9.
doi: 10.1016/j.thromres.2010.05.008
Furukawa S, Nogami K, Shimonishi N, Nakajima Y, Matsumoto T, Shima M. Prediction of the haemostatic effects of bypassing therapy using comprehensive coagulation assays in emicizumab prophylaxis-treated haemophilia A patients with inhibitors. Br J Haematol. 2020. https://doi.org/10.1111/bjh.16574 .
doi: 10.1111/bjh.16574
pubmed: 32162680
Ochi S, Takeyama M, Shima M, Nogami K. Plasma-derived factors VIIa and X mixtures (Byclot((R))) significantly improve impairment of coagulant potential ex vivo in plasmas from acquired hemophilia A patients. Int J Hematol. 2020;111:779–85.
doi: 10.1007/s12185-020-02837-6
Shinkoda Y, Shirahata A, Fukutake K, Takamatsu J, Shima M, Hanabusa H, et al. A phase III clinical trial of a mixture agent of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors. Haemophilia. 2017;23:59–66.
doi: 10.1111/hae.13050
Nogami K, Shima M. New therapies using nonfactor products for patients with hemophilia and inhibitors. Blood. 2019;133:399–406.
doi: 10.1182/blood-2018-07-820712
Haku J, Nogami K, Matsumoto T, Ogiwara K, Shima M. Optimal monitoring of bypass therapy in hemophilia A patients with inhibitors by the use of clot waveform analysis. J Thromb Haemost. 2014;12:355–62.
doi: 10.1111/jth.12488