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Assistant Professor Department of Pharmacy Practice School of Pharmacy Howard University Washington, DC 20059-0001 FAX 202/806-4478 dbernard{at}howard.edu
PharmD Student School of Pharmacy Howard University
PharmD Student School of Pharmacy Howard University
Published Online, November 5, 2003. www.theannals.com, DOI 10.1345/aph.1A372a
There is question regarding the number of patients outside of the defined
stable INR range of 2–3 observed during the study period. Patients with
an INR of 3.0 on day 3 who experienced a further increase in their INR to 3.5
on day 4 were included in the 63% of patients who attained a stable INR. In
practice, however, an INR of 3.5 may be considered overanticoagulation and
warrant some intervention. Also, it is unclear as to what group patients with
an INR of 3.5–3.9 were included. Were they also considered as having a
stable INR since overanticoagulation was defined as an INR 
4?
There is no mention of the incidence of minor and major bleeding observed.
This is of particular interest due to the possible association of age as a
risk factor for bleeding in the elderly population. The study noted 4 of the 5
patients experiencing an INR 4 at completion of the loading dose protocol
as being >65 years of age, further suggesting that the elderly appear to
have a more exaggerated response to therapy.
Many practitioners in the US do not routinely follow a protocol in initiating warfarin therapy due to potential bleeding complications that have developed shortly beyond the designated initiation period. An understanding of the pharmacokinetic profile of warfarin enables clinicians to realize that the full effect of initiation doses may take 10–12 days to be seen due to the prolonged half-life of certain clotting factors being inhibited. To have a patient quickly reach a target INR within a 1-week period may seem desirable, but it is imperative that the INR is reevaluated 3–5 days later to ensure that overanticoagulation has not occurred. The concept of administering a loading dose of warfarin, as promoted by the authors, may be a potential danger in terms of overanticoagulation and is not commonly practiced by many clinicians.
Lastly, the association of low serum albumin levels with an exaggerated warfarin response may influence practitioners in their dosing decisions.2 However, it should be noted that low serum albumin levels resulting in an increased free fraction of warfarin is accompanied by an increase in plasma clearance of the drug, with no effect on the INR, and is clinically irrelevant.3
References
Related articles in The Annals:
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