BLOCKING OF TISSUE FACTOR PATHWAY INHIBITOR (TFPI) SHORTENS THE BLEEDING-TIME IN RABBITS WITH ANTIBODY-INDUCED HEMOPHILIA-A

Tissue factor (TF)/FVIIa initiates coagulation by activating factor IX (FIX) and factor X (FX). Tissue factor pathway inhibitor (TFPI)-FXa c omplexes form and inhibit TF/FVIIa. Blocking of TFPI may facilitate ha emostasis initiated by FVIIa/TF thereby compensating for impaired FIX/ FVIII-dependent coagulation. This hypothesis was tested in a study usi ng rabbits made temporarily haemophilic by the injection of antibodies against FVIII. These rabbits were given i.v. injections of anti-TFPI IgG antibodies and 40 min later bleeding was initiated by cutting the nail including the apex of the cuticle. Injection of anti-TFPI IgG sho rtened the bleeding time significantly from 26 min to Il min (normal m ean bleeding time in non-haemophilia rabbits: 5 min). Treatment with a nti-TFPI IgG also resulted in a shortening of the haemophilic aPTT to a level slightly longer than the normal aPTT. In addition, the prolong ed dilute TF clotting time was shortened by the anti-TFPI IgG treatmen t. Thus, both bleeding and coagulation parameters indicated that block ing of TFPI may be potentially haemostatic in haemophilia.