title: Blocking of tissue factor pathway inhibitor (TFPI) shortens the bleeding time in rabbits with antibody induced haemophilia A.
abstract: Tissue factor (TF)/FVIIa initiates coagulation by activating factor IX (FIX) and factor X (FX). Tissue factor pathway inhibitor (TFPI)-FXa complexes form and inhibit TF/FVIIa. Blocking of TFPI may facilitate haemostasis initiated by FVIIa/TF thereby compensating for impaired FIX/FVIII-dependent coagulation. This hypothesis was tested in a study using 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 shortened the bleeding time significantly from 26 min to 11 min (normal mean bleeding time in non-haemophilia rabbits: 5 min). Treatment with anti-TFPI IgG also resulted in a shortening of the haemophilic aPTT to a level slightly longer than the normal aPTT. In addition, the prolonged dilute TF clotting time was shortened by the anti-TFPI IgG treatment. Thus, both bleeding and coagulation parameters indicated that blocking of TFPI may be potentially haemostatic in haemophilia.
authors.affiliation: Novo Nordisk A/S, Bagsvaerd, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Erhardtsen
authors.forename: M
authors.initials: M
authors.lastname: Ezban
authors.forename: M T
authors.initials: MT
authors.lastname: Madsen
authors.forename: V
authors.initials: V
authors.lastname: Diness
authors.forename: S
authors.initials: S
authors.lastname: Glazer
authors.forename: U
authors.initials: U
authors.lastname: Hedner
authors.forename: O
authors.initials: O
authors.lastname: Nordfang
mesh_terms: D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D001760:Bleeding Time; D001777:Blood Coagulation; D004195:Disease Models, Animal; D005169:Factor VIII / Q000276:immunology*; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008074:Lipoproteins / Q000037:antagonists & inhibitors*; D010314:Partial Thromboplastin Time; D011817:Rabbits; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005169:Factor VIII; D013925:Thromboplastin