Warfarin Sensitivity
Label Mnemonic: WARFSENS
Epic Lab Code: LAB4275
Downtime Form: A-1a Miscellaneous Request
Commercial Mail-out Laboratory
5231 RCP
356-8593
Specimen(s):
Whole Blood
Collection Medium:
Lavender top tube 3 mL (EDTA)
Alternate Collection Media:
Pink top tube 6 mL (K2-EDTA)
Minimum:
Preferred Minimum: 3 mL whole blood in lavender top (EDTA) tube
Absolute Minimum: 1 mL whole blood in lavender top (EDTA) tube
Rejection Criteria:
Plasma or serum. Heparinized specimens.
Testing Schedule:
Testing performed Mondays and Thursdays at reference laboratory.
Turn Around Time:
5-10 days upon receipt at reference laboratory.
Reference Range:
By report.
Interpretive Data:
Background Information for Cytochrome P450 2C9, CYP2C9, 2 Variants Characteristics: The cytochrome P450 (CYP) isozyme 2C9 is involved in the metabolism of many drugs such as warfarin, phenytoin, tolbutamide, glipizide, ibuprofen, and phenobarbital. Variants of CYP2C9 will influence pharmacokinetics of CYP2C9 substrates, and may predict non-standard dose requirements. Incidence: Autosomal co-dominant. Cause: CYP2C9 gene variants result in decreased or complete deficiency in enzyme activity. Variants Tested: (Variants are numbered according to NM_000771 transcript) Decreased function: *2 (rs1799853, c.430C>T). Non-functional: *3 (rs1057910, c.1075A>C). Negative: No variants detected is predictive of *1 functional alleles and normal enzymatic activity. Allele Frequencies: CYP2C9 *2: Caucasians 13 percent, Asians<1 percent, African Americans 3 percent. CYP2C9 *3: Caucasians 7 percent, Asians 4 percent, African Americans 2 percent. Clinical Sensitivity: Drug-dependent. Methodology: Polymerase chain reaction (PCR) and fluorescence monitoring. Analytical Sensitivity and Specificity: Greater than 99 percent. Limitations: Only the targeted CYP2C9 variants will be detected by this panel. Diagnostic errors can occur due to rare sequence variations. Risk of therapeutic failure or adverse reactions with CYP2C9 substrates may be affected by genetic and non-genetic factors that are not detected by this test. This result does not replace the need for therapeutic drug or clinical monitoring. Background Information for Warfarin Sensitivity by VKORC1, 1 Variant Characteristics: Warfarin sensitivity can lead to a life-threatening overdose event such as excessive bleeding. Genetic variation is recognized to explain a large proportion of variability in warfarin dose requirements. This test may predict individual warfarin sensitivity and non-standard dose requirements. The VKORC1 test should be performed in combination with the CYP2C9 test for application to warfarin dose estimates. Inheritance: Autosomal co-dominant. Cause: The VKORC1*2 allele is associated with reduced expression of the warfarin target, vitamin K epoxide reductase (VKOR), and a reduced dose requirement. CYP2C9 gene variants result in decreased or complete deficiency in enzyme activity that will reduce metabolism and prolong the half-life of warfarin. Variants Tested: VKORC1*2 (rs9923231, c.-1639G>A). (Note: Variant is numbered according to VKORC1transcript NM_024006.) Negative: No variant detected is predictive of *1 functional allele and normal VKOR expression. Allele Frequencies: VKORC1*2: Caucasians 39 percent, Asians 91 percent, African Americans 11 percent. Clinical Sensitivity: Approximately 90 percent of CYP2C9 and VKORC1 variants causing warfarin sensitivity in Caucasians are detected when both tests are performed. Less characterized in other populations. Methodology: Polymerase chain reaction(PCR) and fluorescence monitoring. Analytical Sensitivity and Specificity: Greater than 99 percent. Limitations: Only the targeted VKORC1 variant will be detected by this test. Diagnostic errors can occur due to rare sequence variations. Risk of therapeutic failure or adverse reactions with warfarin may be affected by genetic and non-genetic factors that are not detected by this test. This result does not replace the need for therapeutic drug or clinical monitoring. This test does not identify patients at risk for warfarin resistance.
Methodology:
Polymerase Chain Reaction/Fluorescence Monitoring
CPT Code:
81227, 81355