Adult Preferred Minimum: 3 mL whole blood in lavender top (EDTA) tube Adult Absolute Minimum: 1 mL whole blood in lavender top (EDTA) tube Pediatric Absolute Minimum: 1 mL whole blood in lavender top (EDTA) tube

Background Information for Warfarin Sensitivity (CYP2C9 and VKORC1) 3 Mutations 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). 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.

Mutations other than those targeted will not be detected; analytical sensitivity may be compromised by rare primer or probe site mutations. Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.