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Clinical Pharmacist Repatriation General Hospital Daws Road Daw Park SA 5041 Australia FAX 618 83740225 greg.Roberts{at}rgh.sa.gov.au
Published Online, November 5, 2003. www.theannals.com, DOI 10.1345/aph.1A372b
Bleeding was not an endpoint, but no major bleeds were noted. Of a total of 398 INRs determined in the study, 7 fell to >4, and the longest period a patient was above that level was 2 days. Analyzing any association between INRs >4 and major bleeds in this setting is meaningless due to the low incidence of INRs >4. Few clinicians would have serious concerns regarding transient INRs between 3 and 4, as there is only a marginal increase in bleeding risk, although a dose reduction would generally be appropriate. While 4 of the 5 patients experiencing INRs >4 were >65 years of age, this group represented >60% of the total cohort; it therefore is difficult to read much into this.
Using a tried and proven protocol to initiate warfarin has advantages, but it is clear that at completion of whichever protocol is used, more vigilant monitoring is required until the prescriber establishes a good clinical picture of the patient's stability on warfarin. Initiating warfarin at "low, safe" doses (e.g., 5 mg) and dosing empirically frequently still result in marked episodes of overanticoagulation as discussed in the article.
I strongly reiterate that we should not classify warfarin initiation as loading versus nonloading. In initiating warfarin, we are trying to allow the prescriber to reasonably determine a maintenance dose, without overanticoagulating the patient, in a timely manner. This has to take into account that the final maintenance dose may be as low as 0.5 mg/d or as high as 15 mg/d. Many clinicians believe that they have a choice between loading or not loading, but at the time of initiation, we have no indication of whether that first dose will be higher (a loading dose) or lower (a nonloading dose) than the ultimate maintenance dose. If a patient is eventually prescribed a maintenance dose of 1 mg/d, then a 5-mg initiation dose surely represents a significant loading dose, although by current subjective conventions, this is considered as a nonloading dose. Using a tested protocol allows us to respond appropriately to changes in the INR secondary to whatever dose we used during the initiation period (i.e., reasonably predict the next day's dose). The age-adjusted protocol holds little or no danger in terms of overanticoagulation, which is probably its strongest point.
The association of low serum albumin levels and exaggerated warfarin response is likely to result from poor nutritional status and, hence, marginal vitamin K status in these patients.
References
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