Jul 7, 2019
Bioxodes to present up-to-date preclinical data during the annual ISTH congress on Sunday 7 July 2019 in Melbourne
Ir-CPI, a FXIa/FXIIa inhibitor, provides an effective and safe thromboprotection during extracorporeal circulation associated with open-heart surgery
TASSIGNON J1, PIREAUX V1, DEMOULIN S1, BORENSTEIN N2, ENTE A2, FIETTE L2 and GODFROID E1
1Bioxodes, Marche-en-Famenne, Belgium; 2IMMR, Paris, France
Background: Extracorporeal circulation (ECC) during cardiac surgery is a highly thrombogenic procedure involving both intrinsic and extrinsic coagulation pathways and requires strong anticoagulation to prevent thrombosis and to maintain blood fluidity. Unfractionated heparin (UFH) is currently used in such surgical procedures but can lead to serious bleeding complications, highlighting the need for new safer antithrombotic agents. Ir-CPI, a protein from the saliva of tick Ixodes ricinus, is an inhibitor of both FXIIa and FXIa which has been demonstrated to inhibit thrombotic processes in various experimental animal models.
Aims: Our objective was to evaluate the efficacy and safety of Ir-CPI in ECC during cardiac surgery using uncoated adult ECC system.
Methods: An ECC system with uncoated material was used to perform a chordae replacement and a commissuroplasty of the mitral valve on beating heart of sheep. The ECC was maintained for 90 min at full-flow systemic perfusion level. The investigative group received a bolus followed by a continuous intravenous infusion of Ir-CPI. UFH was used as comparator. Following the procedure, half the animals were kept in recovery for 7 days.
Results: Ir-CPI was proven to be as efficient as UFH in preventing clot formation within the ECC circuit. Moreover, Ir-CPI was shown to be as thromboprotective in the animal as UFH with stable physiological parameters (i.e. blood gases, hematology and biochemistry) up to 7 days post-surgery. Oxygenator membrane examination by scanning electron microscopy showed no differences between Ir-CPI and UFH treatment in terms of protein or blood cell deposits. Animals fully recovered after ECC and cardiac surgery and no hemorrhagic and thrombotic related-Ir-CPI findings were observed after histopathological analyses of organs (heart, kidney, lung, liver, brain, spleen and draining lymph nodes).
Conclusion: These results demonstrate for the first time that a FXIa/FXIIa inhibitor alone provides safe thromboprotection in ECC during cardiac surgery.