How factor VIIa works in hemophilia.
The influence of elevated platelet concentration and recombinant factor VIIa (rFVIIa) on thrombin generation at 5 pM tissue factor (TF) in a synthetic mixture corresponding to hemophilia B (SHB) and "acquired" hemophilia B blood (AHBB) produced in vitro by an antifactor IX antibody was evaluated. (a) Thrombin generation in SHB and AHBB was delayed and reduced; (b) with 10 nM rFVIIa or 5x normal platelets (10 x 10(8)/mL) SHB and AHBB showed a slight increase in thrombin generation; (c) in the absence of TF, almost no thrombin generation was detected in SHB and AHBB in the presence of 10 nM rFVIIa and 10 x 10(8)/mL activated platelets (5x normal); (d) with TF, 10 nM rFVIIa and 3-5x normal nonactivated platelets (6-10 x 10(8)/mL), thrombin levels approaching normal values were attained. FVIIa appears to function effectively and locally by the combined effect of TF expression and platelet accumulation at the site of a vascular lesion.
Butenas
S
S
Department of Biochemistry, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405-0068, USA.
Brummel
K E
KE
Bouchard
B A
BA
Mann
K G
KG
D001792:Blood Platelets / Q000502:physiology; D002478:Cells, Cultured; D005167:Factor VII / Q000494:pharmacology*; D015942:Factor VIIa; D002836:Hemophilia B / Q000188:drug therapy* / Q000209:etiology; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D010976:Platelet Count; D011994:Recombinant Proteins / Q000494:pharmacology*; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000502:physiology
D011994:Recombinant Proteins; D005167:Factor VII; D013925:Thromboplastin; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin