Thrombogenicity of a factor IX concentrate quantitated in a canine model.
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.
MacGregor
I R
IR
Scottish National Blood Transfusion Service, Edinburgh, UK.
Ferguson
J F
JF
Dawes
J
J
McLaughlin
L
L
Prowse
C V
CV
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
D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D005344:Fibrinopeptide A; C025667:prothrombin complex concentrates; D005340:Fibrinogen