Regarding the patient who takes a 5-mg warfarin tablet five or six days a week and a half tablet the other days in order to reach a certain international normalized ratio (INR) Item 102-3), what happens if blood is drawn the day after the half tablet dose? Wouldn’t the INR be low and not a true reflection of the patient’s usual INR?
—David A. Lubin, MD, Tampa, Fla.
The desired anticoagulant effect of a given warfarin dose on INR or prothrombin time (PT) is achieved roughly 35-40 hours postingestion. Although warfarin reaches maximum blood levels in 90 minutes and its half-life in circulation is 47 hours, its effect on clotting activity is a function of the half-life of the affected clotting factors. That is to say, new clotting factor molecules synthesized after the warfarin effect lack procoagulant capacity, but those already in circulation do and must be cleared before this anticoagulant effect is exerted. Consequently, in order to measure the anticoagulant effect, the PT test should be performed roughly two days after the given dose is taken and not before. Although INR and PT generally reflect a combined decrease in coagulant activity by (vitamin K-dependent) factors II, VII, and X, factor VII has the shortest half-life (four to six hours), and its decreased activity contributes more to patients’ initial INR or PT than do the other clotting factors affected (factors II and X have half-lives of 60 and 40 hours, respectively). For further information, see Warkentin TE. Thrombotic complications of anticoagulant therapy. In: Colman RW, George JN, Hirsh J, et al. Thrombosis and Hemostasis: Basic Principles and Clinical Practice. 4th ed. Philadelphia, Pa.: Williams & Wilkins; 2001:1371-1382.
—Dennis K. Galanakis, MD, chief of blood services and associate professor of medicine at The State University of New York at Stony Brook (103-20)