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
Naruto ShimonishiMidori Shima

Abstract

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. We have investigated the stability and structure of emicizumab-induced fibrin clots. 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). 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 trig...Continue Reading

References

Jan 1, 1978·Macromolecules·M E Carr, J Hermans
Sep 1, 1995·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·M E Carr, B M Alving
Dec 15, 2005·British Journal of Haematology·Alisa S WolbergMaureane Hoffman
Aug 2, 2006·Journal of Thrombosis and Haemostasis : JTH·T SugoY Sakata
Aug 1, 2007·Journal of Thrombosis and Haemostasis : JTH·J W Weisel
Aug 10, 2007·The New England Journal of Medicine·Marilyn J Manco-JohnsonBruce L Evatt
Sep 21, 2007·Haemophilia : the Official Journal of the World Federation of Hemophilia·K BeetonC A Lee
Oct 13, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Angela M CarterUNKNOWN EuroCLOT Investigators
Apr 2, 2011·Haemophilia : the Official Journal of the World Federation of Hemophilia·Y DargaudC Negrier
Nov 3, 2011·Haemophilia : the Official Journal of the World Federation of Hemophilia·K FischerM P Janssen
Nov 22, 2013·Thrombosis and Haemostasis·Aleksandra AntovicJovan P Antovic
Dec 21, 2013·Journal of Thrombosis and Haemostasis : JTH·C J ReaB Sørensen
Mar 27, 2015·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Rita Marchi, Héctor Rojas
May 26, 2016·The New England Journal of Medicine·Midori ShimaKeiji Nogami
Jul 12, 2017·The New England Journal of Medicine·Johannes OldenburgMidori Shima
Jul 28, 2017·Haemophilia : the Official Journal of the World Federation of Hemophilia·T MatsumotoM Shima
May 2, 2018·Research and Practice in Thrombosis and Haemostasis·L LeongJ W Weisel
Aug 30, 2018·The New England Journal of Medicine·Johnny MahlanguRebecca Kruse-Jarres
Sep 14, 2019·Haemophilia : the Official Journal of the World Federation of Hemophilia·Midori ShimaMasashi Taki

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Antibody Engineering

Antibody engineering technologies are constantly advancing to improve the clinical effectiveness of monoclonal and bispecific antibodies. Discover the latest research on Antibody Engineering here.