Key result
Warfarin therapy was associated with extremely low levels of total protein Z antigen (1% to 16% of normal) compared to healthy donors (mean 2.9 micrograms/mL).
Why the study?
Does warfarin therapy affect plasma protein Z antigen levels compared to normal subjects?
Cross-Sectional (n=480)
Does warfarin therapy affect plasma protein Z antigen levels compared to normal subjects?
Warfarin therapy markedly reduces plasma protein Z antigen levels compared to normal subjects, with a plasma half-life of 2 to 3 days.
Warfarin markedly lowers protein Z antigen; leaves open its contribution to bleeding risk or need for adjusted monitoring.
In contrast to the other well-studied vitamin K-dependent proteins that circulate in plasma, protein Z antigen is much more variable. The concentration in plasmas collected in EDTA from 455 normal, healthy donors is normally distributed with a mean of 2.9 micrograms/mL (46 nmol/L) and a SD of 1.0 microgram/mL (95% interval of 32% to 168% of the mean). No significant correlation to age or sex could be detected. In comparison, the concentration of protein C antigen measured with the same type of assay on the same 455 samples has a log normal distribution with a mean of 4.0 micrograms/mL (65 nmol/L) and a 95% interval of 70% to 138% of the mean. Also in marked contrast to other plasma vitamin K-dependent proteins, the total protein Z antigen level is extremely low in patients on stable warfarin therapy (range 1% to 16% of normal). Moreover, even though greater than 95% of the antigen in normal plasmas adsorbs to barium citrate (a crude reflection of the presence of gamma-carboxyglutamic acid (Gla) residues), in the patients taking warfarin almost all of the small amount of the antigen failed to adsorb, suggesting that virtually no protein Z had its full complement of Gla residues. Total protein C antigen in the same 25 patients averaged 53% of normal (34% to 72%) and 54% (average) of the total remaining antigen still adsorbed to barium citrate. The concentration of protein Z antigen in the plasma of a normal individual given a loading dose of warfarin fell at an initial rate of approximately 20% a day, indicating a plasma half-life (t1/2) of 2 to 3 days.
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Miletich et al. (1987) conducted a cross-sectional in Healthy subjects and patients on warfarin therapy (n=480). Warfarin therapy vs. Normal healthy donors was evaluated on Protein Z antigen concentration. Warfarin therapy was associated with extremely low levels of total protein Z antigen (1% to 16% of normal) compared to healthy donors (mean 2.9 micrograms/mL).
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