Protease nexin-1 inhibitor for the treatment of haemorrhagic disease
The thrombogram of FVIII-KO mice displays a prolonged time to peak and a reduced peak thrombin. The addition of the neutralizing anti-protease nexin-1 (PN-1) antibody enhances thrombin generation in PRP from haemophilia mice. The thrombogram of patient with haemophilia displays prolonged lag time and time to peak and a reduced peak thrombin and a reduced endogenous thrombin potential. As observed with the addition of recombinant FVIII, the neutralizing anti-PN-1 antibody enhances thrombin generation in PRP from patients with haemophilia A. Anti-PN-1 antibody improves thrombin generation in mild and moderate haemophilia patients but not in severe haemophilia patients. These findings establish a requirement for PN-1 inhibition as a specific anticoagulant in platelets and demonstrated that blocking PN-1 have a role in haemorrhagic disease treatment.