FACTOR-VII BINDING TO TISSUE FACTOR IN PLASMA FROM WARFARIN-TREATED INDIVIDUALS

Using enzyme immunoassay, we measured the binding ability of artificia l gamma carboxyglutamic acid (Gla)-domainless-Factor VII (FVII) to tis sue factor (TF) or of Factor VII in 44 patients stabilized by long ter m treatment with warfarin. Purified FVII digested with cathepsin G, th at 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) or pl asma from 8 out of 44 warfarin-treated patients, no FVII clotting acti vity (FVII:c) was detected in the supernatant, whereas FVII antigen (F VI1:ag) and FVII-TF binding remained 19.2% and 17%, respectively, as c ompared with those before adsorption. In the plasma from 44 warfarin-t reated patients the FVII:c (mean +/- SD, 54.26+/-12.50%) was significa ntly lower than the FVII:ag (77.15+/-18.24%) (p<0.001), although the F VII :c was significantly correlated with FV11:ag (r=0.628). FVII-TF bi nding (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 digest ed with cathepsin G loses both the clotting activity and the binding a bility to TF. However, PIVKA-VII has little or no clotting activity bu t the binding ability to TF. This suggested that the low specific acti vity of FVII (FVII:c/FVII:ag) in the plasma of warfarin-treated patien ts would not entirely depend on the decreased FVII-TF binding.