Suppression of plasma-activated factor VII levels by warfarin therapy.
To investigate the effect of warfarin treatment on the early phase of tissue factor-induced coagulation, we measured plasma-activated factor VII (factor VIIa) levels by a direct fluorogenic assay in 74 cardiovascular disease patients on long-term oral anticoagulation. We divided the patients into three groups based on the international normalized ratio (INR). In the patients with INR ranges of < 1.7 and 1.7 to 2.5, factor VIIa levels were 42% and 61% lower, respectively, than in age- and sex-matched controls. Factor VII coagulant activity (factor VIIc), factor VII antigen (factor VIIag), protein C, and factor X levels were also reduced to a similar extent in both groups. However, in patients with an INR > 2.5, the factor VIIa level was not decreased compared with that at an INR of 1.7 to 2.5, although the factor VIIc, factor VIIag, factor X, and protein C levels were all decreased further. Although the precise relation between the reduction of factor VIIa levels and the increase of INR requires appropriately designed long-term clinical trials, our data suggest that an INR range of 1.7 to 2.5 is sufficient for the suppression of factor VIIa. During the long-term follow-up of three patients with congenital antithrombin III or protein C deficiency, the factor VIIa level was more responsive to changes in the warfarin dose than the INR, and there were generally no corresponding changes of the thrombin-antithrombin III complex (TAT) level. However, one patient showed a transient marked increase of factor VIIa during the discontinuation of warfarin that was accompanied by an increase in TAT. Based on these findings, factor VIIa could be useful for monitoring both hypercoagulable and hypocoagulable states.
Sakata
T
T
National Cardiovascular Center, Clinical Laboratory, Suita, Japan.
Kario
K
K
Matsuo
T
T
Katayama
Y
Y
Matsuyama
T
T
Kato
H
H
Miyata
T
T
D000328:Adult; D000368:Aged; D020152:Antithrombin III Deficiency; D015415:Biomarkers / Q000032:analysis; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D015942:Factor VIIa / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020151:Protein C Deficiency; D014859:Warfarin / Q000627:therapeutic use*
D015415:Biomarkers; D014859:Warfarin; D015942:Factor VIIa