title: Inhibition of extrinsic pathway inhibitor shortens the coagulation time of normal plasma and of hemophilia plasma.
abstract: An increasing amount of evidence suggests that coagulation factors VIII and IX play a role not only in the intrinsic but also in the extrinsic pathway of coagulation. In this context the influence of the Extrinsic Pathway Inhibitor (EPI) on the coagulation time of hemophilia plasma lacking FVIII or FIX has been investigated. The coagulation time was measured in a dilute thromboplastin assay. Addition of recombinant EPI (rEPI) prolonged the coagulation time of normal plasma while the addition of an inhibitory antibody against EPI shortened the coagulation time. At low concentrations of thromboplastin the coagulation time of hemophilia plasma was prolonged and at all dilutions of thromboplastin, addition of anti-EPI IgG normalized the coagulation time of a hemophilia plasma. Analysis of 10 individual donor plasma samples and 8 individual hemophilia samples showed that addition of anti-EPI IgG shortened the coagulation time more in hemophilia plasma than in normal plasma. This illustrates the importance of a powerful extrinsic FVII dependent pathway to achieve hemostasis in the case of FVIII or FIX deficiency (hemophilia A and B).
authors.affiliation: Novo Nordisk A/S, Gentofte, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Nordfang
authors.forename: S
authors.initials: S
authors.lastname: Valentin
authors.forename: T C
authors.initials: TC
authors.lastname: Beck
authors.forename: U
authors.initials: U
authors.lastname: Hedner
mesh_terms: D000918:Antibody Specificity / Q000276:immunology; D001777:Blood Coagulation; D005167:Factor VII / Q000037:antagonists & inhibitors* / Q000276:immunology; D006467:Hemophilia A / Q000097:blood*; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D008074:Lipoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D010314:Partial Thromboplastin Time; D011480:Protease Inhibitors / Q000276:immunology*; D012016:Reference Values; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000276:immunology; D013997:Time Factors
chemical_list: D007074:Immunoglobulin G; D008074:Lipoproteins; D011480:Protease Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D013925:Thromboplastin