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Thrombogenicity of a factor IX concentrate quantitated in a canine model
I R MacGregor1, J F Ferguson, J Dawes
1Scottish National Blood Transfusion Service, Edinburgh, UK.
Summary
A canine model using beagles effectively identified thrombogenic risks of factor IX concentrate. This study highlights the beagle model
Area of Science:
- Hematology
- Pharmacology
- Toxicology
Background:
- Factor IX concentrate is crucial for treating hemophilia but carries thrombogenic risks.
- Assessing the thrombogenicity of factor IX concentrate requires reliable preclinical models.
Purpose of the Study:
- To evaluate a canine non-stasis model for its sensitivity in detecting thrombogenic activity of factor IX concentrate.
- To determine dose-related hemostatic alterations induced by factor IX concentrate in dogs.
Main Methods:
- Dose-ranging studies were conducted in beagles and greyhounds using factor IX concentrate (50-200 IU/kg) over 30 minutes.
- Hemostatic parameters, including plasma fibrinogen, fibrin(ogen) degradation products, and fibrinopeptide A, were monitored for 150 minutes.
- Urinary fibrinopeptide A was also measured as a potential marker of thrombogenicity.
Main Results:
- Beagles exhibited greater sensitivity to factor IX concentrate than greyhounds, showing dose-related increases in fibrin(ogen) degradation products and decreases in fibrinogen (50-150 IU/kg).
- Plasma fibrinopeptide A was the most sensitive marker, with significant elevations observed at 50 IU/kg factor IX concentrate compared to albumin controls.
- Urinary fibrinopeptide A levels did not correlate with thrombogenicity in this model.
Conclusions:
- The beagle non-stasis model is a sensitive method for quantifying thrombogenic activities of factor IX concentrates.
- This model can aid in assessing the safety of high-dose factor IX concentrate formulations.
- Plasma fibrinopeptide A is a reliable indicator of coagulation activation in this canine model.