Recombinant human factor VIIa (rFVIIa) in a rabbit stasis model.
The thrombogenicity of recombinant human FVIIa (rFVIIa) and FEIBA was studied in a rabbit stasis model. Only minor thrombus formation in isolated vein segments during 10 min. of stasis was seen following the administration of rFVIIa 100-1000 micrograms/kg or FEIBA 50-100 U/kg whereas both compounds caused clear thrombus formation during 30 min. of stasis. RFVIIa caused no change in platelet counts or plasma fibrinogen 3 hours after administration, whereas a small decrease of APTT was seen due to the direct effect of rFVIIa in this assay. In contrast, FEIBA caused a significant and dose-dependent decrease of platelet counts as well as of fibrinogen, and an increase of APTT which demonstrate a general consumption of coagulation factors. In conclusion the study demonstrated a local pharmacological effect of rFVIIa in the absence of a general activation of the coagulation cascade.
Diness
V
V
Novo Nordisk A/S, Bagsvaerd, Denmark.
Bregengaard
C
C
Erhardtsen
E
E
Hedner
U
U
D000818:Animals; D001779:Blood Coagulation Factors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000494:pharmacology*; D005340:Fibrinogen / Q000032:analysis; D006487:Hemostasis; D006801:Humans; D010314:Partial Thromboplastin Time; D010976:Platelet Count / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; D005340:Fibrinogen; C065655:anti-inhibitor coagulant complex; D015942:Factor VIIa