title: Prophylactic effect of recombinant factor VIIa in factor VII deficient patients.
abstract: Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder associated with a bleeding tendency. We describe three patients with congenital FVII deficiency who have been treated with activated recombinant factor VII (rVIIa). Two patients had novel mutations and were treated prophylactically with 1.2 mg rVIIa two to three times a week. Patients 1 and 2 had a severe bleeding tendency. The frequency and severity of bleeding decreased by treatment with rVIIa compared with similar treatment with plasma-derived FVII. The third patient with a moderate bleeding phenotype was treated on demand and showed no change in the frequency of bleeding upon treatment with rVIIa or plasma products. The beneficial effect of rVIIa cannot be explained by the rVIIa half-lives. Pharmacokinetical analysis showed rVIIa activity half-lives of 35, 50 and 54 min for patients 1, 2 and 3, respectively. In conclusion, prophylactic treatment of FVII deficient patients with rVIIa appears to be applicable, safe and successful, although the mechanism of action remains to be elucidated.
authors.affiliation: Central Haematology Laboratory, UMC St Radboud Nijmegen, Nijmegen, The Netherlands. N.Mathijssen@chl.umcn.nl
authors.forename: Natascha C J
authors.initials: NC
authors.lastname: Mathijssen
authors.forename: Rosalinde
authors.initials: R
authors.lastname: Masereeuw
authors.forename: Kitty
authors.initials: K
authors.lastname: Verbeek
authors.forename: J Maurice
authors.initials: JM
authors.lastname: Lavergne
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Costa
authors.forename: Waander L
authors.initials: WL
authors.lastname: van Heerde
authors.forename: Irena R O
authors.initials: IR
authors.lastname: Nováková
mesh_terms: D002648:Child; D005165:Factor V / Q000032:analysis; D005167:Factor VII / Q000235:genetics / Q000627:therapeutic use; D005168:Factor VII Deficiency / Q000235:genetics / Q000628:therapy*; D015942:Factor VIIa / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006207:Half-Life; D006470:Hemorrhage / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; C095381:factor V Leiden; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D015942:Factor VIIa