Jul 10, 2017
Bioxodes to present preclinical data for its main product, Ir-CPI, at ISTH 2017 annual congress.
Efficacy of a novel contact pathway inhibitor, Ir-CPI, on in vitro clotting induced by PCI catheter segment
Douxfils J1, Gheldof D1, Derochette S2, Tassignon J2, Meinguet C2, Guyaux M2, Dogné J-M1, Godfroid E2
1Department of Pharmacy, University of Namur, Belgium; 2Bioxodes, Marche en Famenne, Belgium
Background: Ir-CPI, a protein derived from the tick Ixodes ricinus salivary, is a serine protease inhibitor of both factor XIa (FXIa) and FXIIa. In patients undergoing percutaneous coronary intervention (PCI), catheter thrombosis may occur as catheters trigger activation of FXII/FXI.
Aims: The aim of this study was to evaluate the effect of Ir-CPI on in vitro clotting induced by PCI catheter segment.
Methods: Catheter segments were pressed flat, shaped into rings and placed around the perimeter of wells (96-well plate), leaving the center of the well unobstructed. To the wells were added serial dilution of Ir-CPI (until 10 µM) with normal pooled plasma (NPP) or plasmas deficient in FXI or FXII. After incubation at 37°C and addition of a CaCl2 solution, clot formation was assessed by monitoring absorbance at 340nm. Time to reach one-half maximal absorbance (IC50) was defined as the clotting time. Thrombin generation test (TGT) was also assessed using catheter segment as trigger of the process. Positive inhibitory controls were used (fondaparinux, enoxaparin).
Results: Presence of the catheter reduced the clotting time of NPP; an effect reversed by the addition of Ir-CPI. At high concentrations (≥ 5µM), Ir-CPI allowed to overpass the clotting time without catheter. On TGT (Figure 1), catheter segments decreased lag time and time to peak while the endogenous thrombin potential (ETP) and the peak were increased. The presence of Ir-CPI allowed the restoration of baseline value, i.e. value of the NPP without exposition to catheter segments, in a concentration-dependent manner. When clotting was triggered with FXII deficient plasma, we confirmed that catheter thrombosis is linked to FXI activation and that clotting can be abrogated with 3µM of Ir-CPI.
Conclusion: Ir-CPI can be used to inhibit the clotting induced by catheter segments and achieve antithrombotic effect. Ir-CPI is a promising agent with a better safety profile than heparins to face the problem of catheter thrombosis during PCI procedures.Return