A young male developed spontaneous DVT of right lower limb and he is having a sister who had DVT 5 years back and having protein C deficiency. He was started on warfarin and the INR came to 2-3 after which he had started following at local hospital where his warfarin dose was steadily increased as his INR never went higher than 1.5 and is currently on warfarin dose of 20 mg/day. He was referred back to hospital and was evaluated and found to be having warfarin level of 2.385 mg/l (therapeutic range 0.7 – 2.3 mg/l), PIVKA is > 10 (Ref. range < 0.2). What is the most likely explanation for the subtherapeutic INR?
a. Cytochrome p450 mutation
b. VKORC 1 mutation
c. Not taking warfarin
d. Local hospital INR testing quality control is not good
The most likely explanation for the subtherapeutic INR despite high doses of warfarin and elevated warfarin levels is:
b. VKORC 1 mutation
VKORC1 (Vitamin K epoxide reductase complex subunit 1) mutations can affect how warfarin works in the body, leading to variability in warfarin sensitivity and dosing requirements. The high warfarin dose and subtherapeutic INR suggest that the patient may have a VKORC1 mutation, which could make him less responsive to the drug and necessitate higher doses to achieve therapeutic INR levels.