| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5621878 | Thrombosis Research | 2017 | 7 Pages |
â¢Eculizumab has an impact on the EV amount in PNH patient plasma.â¢Eculizumab has an impact on the procoagulant profile induced by the EVs.â¢STA®-Procoag PPL could be used to measure the impact of eculizumab on hemostasis.
IntroductionParoxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by the susceptibility of blood cells to attack by the complement system, inducing extracellular vesicle (EV) production. Thromboembolism is the leading cause of death in this condition. Eculizumab, a humanized monoclonal antibody which inhibits the C5 protein of the complement, reduces the thrombotic risk in PNH.Materials and methodWe conducted a pilot, prospective, open-label, longitudinal clinical study with six PNH patients treated with eculizumab. The aim was to measure, by flow cytometry, the EVs' production in the patients' platelet-free plasma (PFP) before and during the treatment. We also assessed the procoagulant activity in PFP using STA®-Procoag-PPL and thrombin generation assays (TGA). A high-sensitive version of TGA was also used to study the procoagulant profile induced by the EVs using EVs pelleted from PFP.ResultsWe observed a decrease in platelet EV count with eculizumab treatment (p < 0.05). STA®-Procoag-PPL assay showed a decrease of the procoagulant profile induced by procoagulant phospholipids (PL) during treatment. These results were not confirmed by TGA on PFP, due to a lack of sensitivity. Thus, we used a high-sensitive version of TGA that enabled us to observe variation in the procoagulant profile induced by the EVs with eculizumab (p < 0.05).ConclusionsEculizumab has an impact on the extent of EV production and on the procoagulant profile induced by the procoagulant PL and the EVs. One factor in the antithrombotic action of eculizumab is its ability to decrease EV production and the procoagulant profile induced by PL and EVs.
