Letters
Hematologic diseases
Volume 191 - Issue 10

Stop taking warfarin? No way!

Authors:  Amit K Verma and Ajai K Verma

Med J Aust 2009; 191 (10): 577-578. || doi: 10.5694/j.1326-5377.2009.tb03325.x
Published online: 16 November 2009
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To the Editor: Brukner’s personal perspective in a recent issue of the Journal highlights the inherent difficulty of managing patients taking warfarin.1 Although Brukner advocates life-long warfarin therapy for patients who have experienced a pulmonary embolism, we believe few clinicians would be willing to expose their patients to the increased risk of haemorrhage associated with long-term warfarin therapy, especially if a transient risk factor for venous thromboembolism (VTE) existed (such as frequent air travel, in Brukner’s case).

There is an abundance of conjecture regarding the appropriate duration of warfarin therapy for VTE, with guidelines and clinical intuition often differing. But it is possible that, in the future, decisions about the appropriate duration of warfarin therapy may be guided by the use of pharmacogenetics. Pharmacogenetics gives clinicians an insight into how a patient’s genetic profile affects his or her ability to metabolise drugs, thereby allowing doctors to better tailor the dose and duration of the patient’s medications.

In the case of warfarin, metabolism of S-warfarin (the more potent enantiomer in the racemic warfarin mixture) occurs via the cytochrome P450 system, specifically enzyme CYP2C9.2 Studies have shown that patients who metabolise warfarin normally are homozygous for the wild-type allele CYP2C9*1, whereas patients with polymorphisms in the CYP2C9 allele have reduced warfarin metabolism and increased risk of bleeding.3 The anticoagulation effect of warfarin actually occurs via inhibition of the C1 subunit of the vitamin K 2,3-epoxide reductase complex (VKORC1).4 Numerous polymorphisms have been identified in VKORC1, and it is speculated that VKORC1 polymorphisms alone may account for a significant proportion of response variability to warfarin.4

Validated algorithms have been developed to combine information on a patient’s CYP2C9 and VKORC1 genotypes with factors such as age and body surface area to identify an appropriate warfarin regimen.5 Although the pharmacogenetic information required to employ this algorithm has not been assessed for cost-effectiveness, it is quite possible that clinicians will be able to use such pharmacogenetic information to their advantage in the future. This would allow doctors to identify with greater precision which patients are likely to benefit from warfarin (and how much is required, for how long), rather than relying on equivocal evidence and clinical intuition alone.

Authors

  • Amit K Verma1
  • Ajai K Verma1
  • 1. Monash University, Melbourne, VIC.

Correspondence: amit_verma5@hotmail.com

References

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