Inhibitor of zymogen synthesis :WARFARIN
Time Course
- although the desired INR ratio can vary with the disease being treated, a common goal is to keep the INR value between 2.5 and 3.5
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note that the INR scale (used for the dashed treatment line) is inverted: low values (hypercoagulation) are at the top of the plot; high values (hypocoagulaton) are at the bottom
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- WARFARIN affects zymogen concentrations differentially: factor VII concentrations drop first (t1/2 ~ 6 hr); prothrombin concentrations last
(t1/2 ~ 60 hrs)
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as might be predicted, the change in INR most closely follows the decrease in prothrombin concentration
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- another key point is that WARFARIN causes a decrease in protein C concentrations before prothrombin levels decrease; since protein C is an anticoagulant, this can lead to a TEMPORARY increase in coagulation that can result in cutaneous necrosis (a side effect of WARFARIN)