Factor VII binding to tissue factor in plasma from warfarin-treated individuals.
Using enzyme immunoassay, we measured the binding ability of artificial gamma-carboxyglutamic acid (Gla)-domainless-Factor VII (FVII) to tissue factor (TF) or of Factor VII in 44 patients stabilized by long term treatment with warfarin. Purified FVII digested with cathepsin G, that is Gla-domainless-FVII, showed a rapid loss in the binding ability of FVII to TF (FVII-TF binding). After adsorption with Al(OH)3 of plasma from 8 out of 44 warfarin-treated patients, no FVII clotting activity (FVII:c) was detected in the supernatant, whereas FVII antigen (FVII:ag) and FVII-TF binding remained 19.2% and 17%, respectively, as compared with those before adsorption. In the plasma from 44 warfarin-treated patients the FVII:c (mean +/- SD, 54.26 +/- 12.50%) was significantly lower than the FVII:ag (77.15 +/- 18.24%) (p < 0.001), although the FVII:c was significantly correlated with FVII:ag (r = 0.628). FVII-TF binding (68.27 +/- 21.16%) was significantly higher than FVII:c (p < 0.001), but not than FVII:ag (p > 0.05). The FVII-TF binding was significantly correlated with FVII:ag (r = 0.738), but somewhat poorly with FVII:c (r = 0.415). These results show that artificial Gla-domainless-FVII digested with cathepsin G loses both the clotting activity and the binding ability to TF. However, PIVKA-VII has little or no clotting activity but the binding ability to TF. This suggested that the low specific activity of FVII (FVII:c/FVII:ag) in the plasma of warfarin-treated patients would not entirely depend on the decreased FVII-TF binding.
Takamiya
O
O
Department of Medical Technology, Shinshu University, Matsumoto Asahi, Japan.
Yoshioka
A
A
D000327:Adsorption; D000328:Adult; D000536:Aluminum Hydroxide; D005167:Factor VII / Q000378:metabolism*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013925:Thromboplastin / Q000378:metabolism*; D014859:Warfarin / Q000494:pharmacology*
D014859:Warfarin; D000536:Aluminum Hydroxide; D005167:Factor VII; D013925:Thromboplastin