Case: INR 2.2 but VII and IX are Normal

Here is a puzzler from Pam Owens at Tricore Reference Laboratories in Albuquerque.
Hi George, we recently encountered a patient on warfarin (confirmed by clinician) whose international normalized ratio (INR) is 2.22, protein C and S are in the 30–40% range, but her factors VII and IX are “slam” normal. Have you ever encountered this? What could cause it? We are somewhat mystified given the range of half-lives. Thanks, Pam.

Hi, Pam. No, I have not encountered this. I had the opportunity to pose your question to several colleagues while attending last week’s American Association of Clinical Chemistry and American Society for Clinical Laboratory Science annual meeting in Los Angeles. Nobody had a really good answer there, so I’m just going to take a “scientific wild guess.” I’ll assume the prothrombin (factor II) and factor X activity levels were reduced, and that V and VIII were normal. In that case, I suggest that the patient may have recently discontinued warfarin, which you could check with her or the clinician, and that factors VII and IX, with half-lives of 6 hours and 24 hours, respectively, had recovered whereas factors II and X, half-lives of 60 hours and 48-52 hours had not yet recovered. The low II and X would account for the INR, which should return to normal as their activity levels reach normal. Of course, the weakness in my argument is that protein C, whose half-life is also around 6 hours, should also have returned to normal, so I’ll leave this post open for a better answer!