title: Thrombogenicity of a factor IX concentrate quantitated in a canine model.
abstract: Dose-ranging studies with a batch of factor IX concentrate have been performed in a canine non-stasis model of thrombogenicity. Doses between 50 and 200 IU/kg were infused over a 30 min period, and beagles were found to be more sensitive than greyhounds with regard to subsequent alterations in haemostatic parameters over a 150 min period. In beagles we detected significant increases in plasma fibrin(ogen) degradation products and reduction in fibrinogen concentrations in a dose-related manner after infusion of factor IX concentrate over the range 50-150 IU/kg. Plasma fibrinopeptide A was the most sensitive marker of activation of coagulation with significantly increased levels after factor IX at 50 IU/kg compared with control infusions of albumin. Recovery of infused factor IX was similar to values reported in man. In these experiments, measurement of urinary fibrinopeptide A did not prove to be a useful indicator of thrombogenicity. In conclusion, the beagle non-stasis model will provide a sensitive method to quantify the unwanted thrombogenic activities associated with the use of high doses of certain factor IX concentrates.
authors.affiliation: Scottish National Blood Transfusion Service, Edinburgh, UK.
authors.forename: I R
authors.initials: IR
authors.lastname: MacGregor
authors.forename: J F
authors.initials: JF
authors.lastname: Ferguson
authors.forename: J
authors.initials: J
authors.lastname: Dawes
authors.forename: L
authors.initials: L
authors.lastname: McLaughlin
authors.forename: C V
authors.initials: CV
authors.lastname: Prowse
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D007700:Kinetics
chemical_list: D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D005344:Fibrinopeptide A; C025667:prothrombin complex concentrates; D005340:Fibrinogen