- 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
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)