Exploratory in vitro evaluation of thrombin generation of eptacog beta (recombinant human fviia) and emicizumab in congenital haemophilia A plasma
| Autor: | Jean-Luc Plantier, Daniel Bonzo, J A Grandoni, Veronique Duretz, Sean Evans |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Haemophilia A
haemophilia A Factor VIIa 030204 cardiovascular system & hematology Pharmacology Antibodies Monoclonal Humanized Hemophilia A 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Thrombin Breakthrough bleeding inhibitors Antibodies Bispecific medicine Humans Beta (finance) eptacog beta Genetics (clinical) Emicizumab emicizumab Factor VII biology business.industry Original Articles rFVIIa Hematology General Medicine medicine.disease sevenfact Recombinant Proteins In vitro Laboratory Science chemistry thrombin generation biology.protein Original Article medicine.symptom Antibody business 030215 immunology medicine.drug |
| Zdroj: | Haemophilia |
| ISSN: | 1365-2516 1351-8216 |
| Popis: | Introduction/Aim Eptacog beta is a recombinant activated human factor VII approved to treat and control bleeding in haemophilia A and B patients with inhibitors. Emicizumab is a factor VIIIa mimetic antibody approved for prophylactic treatment of haemophilia A with and without inhibitors (HAI and HA, respectively). Inhibitor patients treated with emicizumab should expect breakthrough bleeding that requires bypassing agent treatment to restore haemostasis. The aim of this study is to quantify the in vitro thrombin generation induced by the addition of eptacog beta to HAI and HA plasma containing emicizumab. Methods Thrombin generation assays were performed using HAI and HA plasma. Thrombin generation parameters were examined using a fixed effects model with inhibitor titre, eptacog beta concentration and emicizumab concentration as main effects, and eptacog beta concentration with inhibitor and emicizumab concentration with inhibitor as interaction effects. Results A significant increase in peak thrombin, ETP and velocity was observed when combinations of eptacog beta (0, 1, 2 or 5 µg/ml) and emicizumab (0, 50 or 100 µg/ml) were evaluated in HA and HAI plasma; the effect remained below that observed in Normal Plasma (NP). A small shortening of lag time below that of NP was observed. Conclusions Eptacog beta and emicizumab induced thrombin generation in haemophilia A plasma (with and without inhibitors) with the thrombin generation parameters remaining below those of normal plasma. These data provide in vitro proof of concept supporting the concept of use of eptacog beta for the treatment and control of breakthrough bleeding in patients on emicizumab prophylaxis. |
| Databáze: | OpenAIRE |
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