The in vitro effect of anticoagulant agents on coagulation and fibrinolysis in the presence of emicizumab in the plasmas from patients with haemophilia A.
anticoagulants
bispecific antibody
coagulation
fibrinolysis
hemophilia A
infection
Journal
Haemophilia : the official journal of the World Federation of Hemophilia
ISSN: 1365-2516
Titre abrégé: Haemophilia
Pays: England
ID NLM: 9442916
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
11
09
2023
received:
05
07
2023
accepted:
19
09
2023
medline:
14
11
2023
pubmed:
28
9
2023
entrez:
28
9
2023
Statut:
ppublish
Résumé
Emicizumab is used as hemostatic prophylaxis for patients with hemophilia A (PwHA), irrespective of the presence of inhibitors. Although bacterial infection can lead to a procoagulant state, there is limited information on coagulation and fibrinolysis potentials in emicizumab-treated PwHA and on the use of anticoagulants in such cases. We examined whether anticoagulants affect the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab. Plasma from PwHA was in vitro supplemented with emicizumab (50 μg/mL; emi-plasma) and anticoagulants (recombinant thrombomodulin (rTM), nafamostat mesylate (NM), unfractionated heparin (UFH), or low-molecular-weight heparin (LMH)). PwHA plasma spiked with rFVIII (1 IU/mL) was used as a reference (ref-plasma). The coagulation and fibrinolysis potentials in plasma was measured by thrombin and plasmin generation assay (T/P-GA) and clot-fibrinolysis waveform analysis (CFWA). In T/P-GA and CFWA, coagulation potentials (maximum coagulation velocity; |min1|, and peak thrombin; Th-Peak) in plasma rose with increasing concentrations of emicizumab and rFVIII, but fibrinolytic potentials (peak plasmin; Plm-Peak, and maximum fibrinolytic velocity; |FL-min1|) remained unchanged. Adding rTM, NM, and UFH to emi-plasma suppressed coagulation and fibrinolysis potentials, similar to ref-plasma. Regarding the heparin, UFH and LMH inhibited the improved coagulation in emi-plasma. UFH inhibited fibrinolysis as well, but LMH did not. Anticoagulants could exhibit the inhibitory effects on the coagulation and fibrinolysis potentials in plasma from PwHA spiked with emicizumab, similar to those in normal plasma.
Substances chimiques
Anticoagulants
0
emicizumab
7NL2E3F6K3
Heparin
9005-49-6
Thrombin
EC 3.4.21.5
Fibrinolysin
EC 3.4.21.7
Antibodies, Bispecific
0
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1529-1538Subventions
Organisme : Chugai Pharmaceutical Co., Ltd.
Organisme : Grant-in-Aid for Scientific Research
ID : 22K16330
Informations de copyright
© 2023 John Wiley & Sons Ltd.
Références
Kitazawa T, Igawa T, Sampei Z, et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nat Med. 2012;18:1570-1574.
Sampei Z, Igawa T, Soeda 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.
Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017;117:1348-1357.
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia with inhibitors. N Engl J Med. 2017;377:809-818.
Young G, Liesner RI, Chang T, et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019;134:2127-2138.
Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379:811-822.
Pipe SW, Shima M, Lehle M, 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-e305.
Yang R, Wang S, Wang X, et al. Prophylactic emicizumab for hemophilia A in the Asia-Pacific region: a randomized study (HAVEN 5). Res Pract Thromb Haemost. 2022;6:e12670.
Négrier C, Mahlangu J, Lehle M, et al. Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. Lancet Haematol. 2023;10:e168-e177.
Shima M, Nogami K, Nagami S, 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;25:979-987.
Jiménez-Yuste V, Peyvandi F, Klamroth R, et al. Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: a phase 3b, multicenter, single-arm study (STASEY). Res Pract Thromb Haemost. 2022;6:e12837.
Caroline W, Hua X, Ben P, et al. Emicizumab prophylaxis in haemophilia A with inhibitors: three years follow-up from the UK Haemophilia Centre Doctors’ Organisation (UKHCDO). Haemophilia. 2023;29:743-752.
Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727-733.
Ciceri F, Beretta L, Scandroglio AM, et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020;22:95-97.
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-847.
Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e24S-43S. Suppl.
Walenga JM, Lyman GH. Evolution of heparin anticoagulants to ultra-low-molecular-weight heparins: a review of pharmacologic and clinical differences and applications in patients with cancer. Crit Rev Oncol Hematol. 2013;88:1-18.
Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699-709.
Hitomi Y, Ikari N, Fujii S. Inhibitory effect of a new synthetic protease inhibitor (FUT-175) on the coagulation system. Haemostasis. 1985;15:164-168.
Nogami K, Matsumoto T, Sasai K, et al. A novel simultaneous clot-fibrinolysis waveform analysis for assessing fibrin formation and clot lysis in haemorrhagic disorders. Br J Haematol. 2019;187:518-529.
Matsumoto T, Nogami K, Shima M. Simultaneous measurement of thrombin and plasmin generation to assess the interplay between coagulation and fibrinolysis. Thromb Haemost. 2013;110:761-768.
Takeyama M, Sasai K, Matsumoto T, et al. Comprehensive blood coagulation potential in patients with acquired hemophilia A: retrospective analyses of plasma samples obtained from nationwide centers across Japan. Int J Hematol. 2022;115:163-172.
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;127:1633-1641.
Mimms LT, Zampighi G, Nozaki Y, Tanford C, Reynolds JA. Phospholipid vesicle formation and transmembrane protein incorporation using octyl glucoside. Biochemistry. 1981;20:833-840.
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;26:215-223.
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;10:2338-2343.
Schmitt C, Adamkewicz JI, Xu J, et al. Pharmacokinetics and pharmacodynamics of emicizumab in persons with hemophilia a with factor VIII inhibitors: HAVEN 1 study. Thromb Haemost. 2021;121:351-360.
Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2013;13:34-45.
Bonaventura A, Vecchie A, Dagna L, et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol. 2021;21:319-329.
Loo J, Spittle DA, Newnham M. COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms. Thorax. 2021;76:412-420.
Rivas-Pollmar MI, Alvarez-Roman MT, Butta-Coll NV, et al. Thromboprophylaxis in a patient with COVID-19 and severe hemophilia A on emicizumab prophylaxis. J Thromb Haemost. 2020;18:2202-2204.
Fogarty PF, Mancuso ME, Kasthuri R, et al. Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international, retrospective, 10-year survey. Haemophilia. 2015;21(5):589-597.
Massimo F, Pier Mannuccio M. Co-morbidities and quality of life in elderly persons with haemophilia. Br J Haematol. 2010;148:522-533.
Roger EGS, Victor JY, Miguel E, et al. Antithrombotic treatment in patients with hemophilia: an EHA-ISTH-EAHAD-ESO clinical practice guidance. Hemasphere. 2023;7:e900.
Cedric H. Venous thromboembolic disease in patients with haemophilia. Thromb Res. 2012;130(1):S50-52. Suppl.
Conway EM. Thrombomodulin and its role in inflammation. Semin Immunopathol. 2012;34:107-125.
Hackert T, Werner J, Gebhard MM, Klar E. Effects of heparin in experimental models of acute pancreatitis and post-ERCP pancreatitis. Surgery. 2004;135:131-138.
Schmidt EP, Yang Y, Janssen WJ, et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med. 2012;18:1217-1223.
Hao C, Xu H, Yu L, Zhang L. Heparin: an essential drug for modern medicine. Prog Mol Biol Transl Sci. 2019;163:1-19.
Van Walderveen MC, Berry LR, Chan AK. Effect of covalent antithrombin-heparin on activated protein C inactivation by protein C inhibitor. J Biochem. 2010;148:255-260.