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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!

Comments (2)
Anticoagulant Therapy
Jul 26, 2012 10:34am

Hmm, I wonder if these results help to strengthen my guess t
Hmm, I wonder if these results help to strengthen my guess that the warfarin had been recently discontinued, as you would anticipate that protein C would recover at nearly the same rate as factor VII.

Jul 25, 2012 11:03am

Hi George,
A little update on this patient. Her Protein S a

Hi George,
A little update on this patient. Her Protein S antigen was decreased as expected, but her Protein C antigen was normal. Makes one think she may have a type 2 deficiency(that would explain that pesky half life issue), but we are recommending the clinician draw no conclusions while she is on warfarin and retest when she has been off an appropriate length of time.

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