Venous Thromboembolism: Warfarin Genetic Variances (recorded lecture)

Question 1

Genetic Variances with CYP2C9

Answer 1

Variance is associated with increased bleeding risk and longer time to goal
CYP2C91: wild type (normal enzyme activity)
CYP2C92 and 3: decrease S-warfarin clearance 40%-70% and 90% respectively
1/2: 20% lower dose requirement
2/3 or 1/3: 35% lower dose requirement
3/3: 80% lower dose requirement
2/3: occurs in 1/3 of white patients
CYP2C95, *6, *8, *11: more common in Asians and AA
*8 allele: 1/9-10 African Americans
Correlates with lower dose requirement

Question 2

Genetic Variance with VKORC1

Answer 2

-1639A and 1173T: decreased VKOR production
Almost always inherited together
-1639A: increased warfarin sensitivity
-1639AA: lower warfarin dose (Asians)
Average daily dose: 3 mg
-1639G: increased warfarin resistance
-1639GG: higher warfarin dose (African Americans)
Average daily dose: 6 mg

Question 3

Who should be tested for genetic variance?

Answer 3

If patient is warfarin naive, genetic test results are available before the sixth dose, patient is at high risk of bleeding due to elevated INR