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Emicizumab improves the stability and structure of fibrin clot derived from factor VIII‐deficient plasma, similar to the addition of factor VIII
Author(s) -
Shimonishi Naruto,
Nogami Keiji,
Ogiwara Kenichi,
Matsumoto Tomoko,
Nakazawa Fumie,
Soeda Tetsuhiro,
Hirata Michinori,
Arai Nobuo,
Shima Midori
Publication year - 2020
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.13961
Subject(s) - fibrin , coagulation , fibrinolysis , fibrinogen , chemistry , thromboplastin , partial thromboplastin time , plasmin , hemostasis , immunology , medicine , biochemistry , enzyme
Emicizumab is an antifactor (F)IXa/FX bispecific antibody, mimicking FVIIIa cofactor function. Emi prophylaxis effectively reduces bleeding events in patients with haemophilia A. The physical properties of emicizumab‐induced fibrin clots remain to be investigated, however. Aim We have investigated the stability and structure of emicizumab‐induced fibrin clots. Methods Coagulation was initiated by activated partial thromboplastin time (aPTT) trigger and prothrombin time (PT)/aPTT‐mixed trigger in FVIII‐deficient plasma with various concentrations of emicizumab or recombinant FVIII. The turbidity and stability of fibrin clots were assessed by clot waveform and clot‐fibrinolysis waveform analyses, respectively. The resulting fibrin was analysed by scanning electron microscopy (SEM). Results Using an aPTT trigger, the turbidity was decreased and the fibrinolysis times were prolonged in the presence of emicizumab dose‐dependently. Scanning electron microscopy imaging demonstrated that emicizumab improved the structure of fibrin network with thinner fibres than in its absence. Although emicizumab shortened the aPTT dramatically, the nature of emicizumab‐induced fibrin clots did not reflect the hypercoagulable state. Similarly, using a PT/aPTT‐mixed trigger that could evaluate potential emicizumab activity, emicizumab improved the stability and structure of fibrin clot in a series of experiments. In this circumstance, fibrin clot properties with emicizumab at 50 and 100 µg/mL appeared to be comparable to those with FVIII at ~12 and ~24‐32 IU/dL, respectively. Conclusion Emicizumab effectively improved fibrin clot stability and structure in FVIII‐deficient plasma, and the physical properties of emicizumab‐induced fibrin clots were similar to those with FVIII.