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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.
Haemophilia. 2020 May; 26(3):e97-e105.H

Abstract

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.

Authors+Show Affiliations

Department of Pediatrics, Nara Medical University, Kashihara, Japan.Department of Pediatrics, Nara Medical University, Kashihara, Japan.Department of Pediatrics, Nara Medical University, Kashihara, Japan.Department of Pediatrics, Nara Medical University, Kashihara, Japan.Sysmex Corporation, Kobe, Japan.Chugai Pharmaceutical Co., Ltd, Kamakura, Japan.Chugai Pharmaceutical Co., Ltd, Kamakura, Japan.Sysmex Corporation, Kobe, Japan.Department of Pediatrics, Nara Medical University, Kashihara, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32157756

Citation

Shimonishi, Naruto, et al. "Emicizumab Improves the Stability and Structure of Fibrin Clot Derived From Factor VIII-deficient Plasma, Similar to the Addition of Factor VIII." Haemophilia : the Official Journal of the World Federation of Hemophilia, vol. 26, no. 3, 2020, pp. e97-e105.
Shimonishi N, Nogami K, Ogiwara K, et al. Emicizumab improves the stability and structure of fibrin clot derived from factor VIII-deficient plasma, similar to the addition of factor VIII. Haemophilia. 2020;26(3):e97-e105.
Shimonishi, N., Nogami, K., Ogiwara, K., Matsumoto, T., Nakazawa, F., Soeda, T., Hirata, M., Arai, N., & Shima, M. (2020). Emicizumab improves the stability and structure of fibrin clot derived from factor VIII-deficient plasma, similar to the addition of factor VIII. Haemophilia : the Official Journal of the World Federation of Hemophilia, 26(3), e97-e105. https://doi.org/10.1111/hae.13961
Shimonishi N, et al. Emicizumab Improves the Stability and Structure of Fibrin Clot Derived From Factor VIII-deficient Plasma, Similar to the Addition of Factor VIII. Haemophilia. 2020;26(3):e97-e105. PubMed PMID: 32157756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Emicizumab improves the stability and structure of fibrin clot derived from factor VIII-deficient plasma, similar to the addition of factor VIII. AU - Shimonishi,Naruto, AU - Nogami,Keiji, AU - Ogiwara,Kenichi, AU - Matsumoto,Tomoko, AU - Nakazawa,Fumie, AU - Soeda,Tetsuhiro, AU - Hirata,Michinori, AU - Arai,Nobuo, AU - Shima,Midori, Y1 - 2020/03/11/ PY - 2020/01/24/received PY - 2020/02/25/revised PY - 2020/02/26/accepted PY - 2020/3/12/pubmed PY - 2020/3/12/medline PY - 2020/3/12/entrez KW - emicizumab KW - fibrin clot structure KW - fibrinolysis KW - haemophilia A KW - scanning electron microscopy SP - e97 EP - e105 JF - Haemophilia : the official journal of the World Federation of Hemophilia JO - Haemophilia VL - 26 IS - 3 N2 - 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. SN - 1365-2516 UR - https://www.unboundmedicine.com/medline/citation/32157756/Emicizumab_improves_the_stability_and_structure_of_fibrin_clot_derived_from_factor_VIII_deficient_plasma_similar_to_the_addition_of_factor_VIII_ L2 - https://doi.org/10.1111/hae.13961 DB - PRIME DP - Unbound Medicine ER -