- Patient Preparation
- Lavender (EDTA) or pink (K2EDTA).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Warfarin overdosing can result in life-threatening events, e.g., bleeding. This test does not identify patients at risk for warfarin resistance.
Incidence: Up to 1 percent mortality and 15 percent morbidity due to bleeding complications.
Cause: Mutations in the CYP2C9 and VKORC1 genes. The common CYP2C9 gene mutations (*2 and *3) with the VKORC1 gene promoter mutation (c.-1639G>A), are estimated to account for 40-63 percent of the variability in therapeutic warfarin dose.
Mutations Tested:CYP2C9 *2 (c.430C>T), CYP2C9 *3 (c.1075A>C), VKORC1 (c.-1639G>A).
(Note: Variants are numbered according to CYP2C9 transcript NM_000771 and VKORC1transcript NM_024006, respectively.)
Allele Frequencies:CYP2C9 *2, 0.08-0.13, 0.02-0.06, and less than 0.01; CYP2C9 *3, 0.06-0.10, less than 0.1, and 0.01-0.04; VKORC1 (c.-1639G>A), 0.42, 0.89, and 0.08 in Caucasian, Asian, and African-American populations, respectively. Other populations are less well characterized. The VKORC1 (c.-1639G>A) is in very strong linkage disequilibrium with the VKORC1 (c.173+1000C>T).
Clinical Sensitivity: 90 percent of CYP2C9 and VKORC1 mutations causing warfarin sensitivity in Caucasians are detected. Less characterized in other populations.
Methodology: Polymerase chain reaction, DNA hybridization, and electrochemical detection.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Mutations other than those targeted will not be detected; analytical sensitivity may be compromised by rare primer or probe site mutations. Diagnostic errors can occur due to rare sequence variations
See Compliance Statement C: www.aruplab.com/CS
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|0051371||VKORC1 Allele 1|
|0051372||VKORC1 Allele 2|
|0051373||Warfarin Sensitivity Interpretation|
|2001336||Warfarin Sensitivity - Specimen|
- Coumadin genotyping
- Cytochrome P450 2C9 Genotyping
- Warfarin sensitiivty genotyping
- Warfarin Sensitivity Genotype by Sequence Analysis, Saliva (Warfarin Sensitivity (CYP2C9 and VKORC1 ) 3 Mutations)