Concizumab, an anti-tissue factor pathway inhibitor antibody, induces increased thrombin generation in plasma from haemophilia patients and healthy subjects measured by the thrombin generation assay.

摘要: Aims Concizumab, a humanized monoclonal antibody against tissue factor pathway inhibitor (TFPI), is being developed as subcutaneously (s.c.) administered treatment for haemophilia. It demonstrated concentration-dependent procoagulant effect in functional TFPI assays; however, global haemostatic assays, such the thrombin generation assay (TGA), offer more complete picture of coagulation. We investigated how concizumab affects following ex vivo spiking plasma from haemophilia patients using TGA, and if can detect multiple s.c. doses healthy subjects. Methods For study, platelet-poor (PPP) 18 with severe was spiked 0.001–500 nm concizumab. For multiple-dosing four males received 250 μg kg−1 every other day eight doses; blood collected before after dosing processed into PPP. In both studies, measured Calibrated Automated Thrombogram® system 1 pm factor. Results In samples patients, peak endogenous potential (ETP) increased concentration dependently, reaching near-normal levels at concentrations >10 nm. Repeated subjects ETP; these effects were sustained throughout interval. Conclusions Thrombin subjects, supporting utility TGA evaluating novel therapy.