Your browser doesn't support javascript.
loading
Emicizumab improves the stability and structure of fibrin clot derived from factor VIII-deficient plasma, similar to the addition of factor VIII.
Shimonishi, Naruto; Nogami, Keiji; Ogiwara, Kenichi; Matsumoto, Tomoko; Nakazawa, Fumie; Soeda, Tetsuhiro; Hirata, Michinori; Arai, Nobuo; Shima, Midori.
Afiliação
  • Shimonishi N; Department of Pediatrics, Nara Medical University, Kashihara, Japan.
  • Nogami K; Department of Pediatrics, Nara Medical University, Kashihara, Japan.
  • Ogiwara K; Department of Pediatrics, Nara Medical University, Kashihara, Japan.
  • Matsumoto T; Department of Pediatrics, Nara Medical University, Kashihara, Japan.
  • Nakazawa F; Sysmex Corporation, Kobe, Japan.
  • Soeda T; Chugai Pharmaceutical Co., Ltd, Kamakura, Japan.
  • Hirata M; Chugai Pharmaceutical Co., Ltd, Kamakura, Japan.
  • Arai N; Sysmex Corporation, Kobe, Japan.
  • Shima M; Department of Pediatrics, Nara Medical University, Kashihara, Japan.
Haemophilia ; 26(3): e97-e105, 2020 May.
Article em En | MEDLINE | ID: mdl-32157756
INTRODUCTION: 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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombose / Fator VIII / Anticorpos Biespecíficos / Anticorpos Monoclonais Humanizados Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombose / Fator VIII / Anticorpos Biespecíficos / Anticorpos Monoclonais Humanizados Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article