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Warfarin Sensitivity

 

Introduction
Warfarin is the most commonly prescribed anti-coagulant and is among the top 20 most prescribed drugs in the US. However, the dose of warfarin required to achieve a stable therapeutic effect varies widely among individuals. The consequences of incorrect dosage are severe and, in some cases, life-threatening. Warfarin is among the top three drugs causing adverse effects requiring hospitalization or emergency room visits, and accounts for 15% of
all drug-related adverse events, second only to digoxin.

 

Warfarin regimens require significant dose adjustments to establish a stable International Normalized Ratio (INR) within a narrow therapeutic range of 2.0 to 3.0. However, approximately 40% of patients on warfarin are outside the therapeutic INR range during the period of adjustment, and are therefore at greater risk of adverse events (such as intracranial hemorrhage and thromboemboletic stroke).1

 

While variation in drug response is caused by many factors such as diet, age, and medications; a patient’s genotype accounts for fully one-third (32%) of the variation.2 This difference in inter-individual genotypes has been shown to affect multiple aspects of the Warfarin response: initial INR, time to stable INR, time to first adverse event, stable/maintenance dose level, 3 time within the therapeutic INR range and number of minor bleeding events.4

Knowing a patient’s genotype before or shortly after administering warfarin can aid physicians in administering the optimal Warfarin dose and potentially reduce the risk of adverse events.

 

Warfarin Sensitivity Genotyping
A patient who is “sensitive” to warfarin requires a lower than average Warfarin dose, especially during the first weeks of treatment. A fast and cost-effective genotyping test is required to enable rapid implementation of the optimal warfarin dose.

 

Patients having the variant *2 or *3 alleles of CYP2C9 and/or the -1639A VKOR allele will require a reduced warfarin dose. The level of dose reduction depends on the number of copies and combination of these alleles. Those patients with a combination of variant CYP2C9 and VKORC1 alleles will require the greatest dose reduction (up to 50%).5

Dosing tools such as warfarindosing.org are currently available to allow physicians to calculate the best starting warfarin dose based on both genotype and clinical factors.

 

Bringing Warfarin Sensitivity Testing into the lab can help:

  • Physicians to identify patients at high-risk for warfarin-related adverse events
  • Physicians to pre-determine early-stage warfarin dosages
  • Reduce hospital costs stemming from adverse events

 

Using the eSensor® XT-8 System for Warfarin Sensitivity† will assist the laboratory in providing:

  • Physicians with life-saving information in about 4 hours for same-day results
  • Accurate and reliable results from the eSensor® Warfarin Sensitivity Test (10 0% accuracy and 100% reproducibility)††

 

Using the eSensor® XT-8 System for Warfarin Sensitivity will allow the laboratory to:

  • Generate easy-to-interpret results on a simple one-page report, including genotypes and a clear “warfarin sensitive” call for patients
  • Reduce technician labor and associated costs with the simple 3-step protocol
  • Adjust workflow as necessary, running samples in batches or random-access
  • Using a touch screen interface instrument approximately the size of a 17” CRT monitor

 

 

 

†   For In Vitro Diagnostic Use
†† 151 samples in a method comparison study and 263 samples in a clinical reproducibility study gave 100%
     concordant results compared to sequencing. Refer to product insert for detailed performance characteristics.

 

1  Menzin, et al. (2005) Ann Pharmacother. 39(3):446-51.
2  Gage, et al. (2008) Clin Pharmacol Ther. Feb 27.
3  Schwarz, et al. (2008) NEJM, 358:999-1008.
4  Caraco et al. (2008) Clin Pharmacol Ther. 83(3):460-70.
5  McClain et al. (2008) Genet Med. 10:89-98.