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 correct answer is:
b. VKORC1 mutation
The patient’s warfarin level is within the therapeutic range, but the INR remains subtherapeutic (below 2). This suggests warfarin resistance. The presence of a high PIVKA (Proteins Induced by Vitamin K Absence) level (> 10) also indicates warfarin resistance.
VKORC1 mutation is a common cause of warfarin resistance, as it affects the warfarin target enzyme, vitamin K epoxide reductase complex subunit 1 (VKORC1).