Comparison of the effect of plasma-derived and recombinant human FVIIa in vitro and in a rabbit model.
Both purified plasma-derived FVIIa (pFVIIa) and recombinant FVIIa (rFVIIa) were shown to shorten the in vitro APTT in haemophilic plasma significantly. After addition of 3.8 micrograms/ml of pFVIIa or rFVIIa, corresponding to 110-140 FVII U/ml, the APTT was normalized in both haemophilia A and haemophilia B plasma. Furthermore, the prolonged APTT in plasma from a patient with acquired inhibitors against FVIII:C was normalized by addition of pFVIIa or rFVIIa in vitro. These results indicate an alternative pathway to the FVII or FVIIa-TF complex formation involving phospholipids (present in the APTT reagent). No signs of systemic activation of the coagulation system in rabbits following infusion of 500, 1000, 5000 U pFVIIa or rFVIIa/kg body weight, corresponding to about 150 micrograms/kg body weight, were seen. This corresponded to 2-3 times the clinical dose of FVIIa.
Hedner
U
U
Biopharmaceuticals Research, Novo Nordisk A/S, Bagsvaerd, Denmark.
Ljundberg
J
J
Lund-Hansen
T
T
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000302:isolation & purification / Q000494:pharmacology*; D005340:Fibrinogen / Q000032:analysis; D006467:Hemophilia A / Q000097:blood*; D002836:Hemophilia B / Q000097:blood*; D006801:Humans; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D005340:Fibrinogen; D015942:Factor VIIa