From Pam Owens at Tricore: We have a specimen from a pregnant patient with a low clottable protein C. Her INR is normal, but she is a heterozygote for both factor V Leiden mutation and the prothrombin 20120 gene mutation. Could the prothrombin gene mutation be interfering with the assay, causing the PC levels to appear lower than they actually are?
Response from Dean Willett, Director of Marketing at Precision BioLogic, regarding theClot C assay:
- Clot C is unaffected by FVIII levels up to 600% so we can probably rule out the possibility that high FVIII levels commonly observed during pregnancy as the main culprit.
- In our Clot C validation studies we did not observe any influence from FV Leiden. A subsequent study published by Peter Cooper from Hallamshire Hospital in the UK, Evaluation of A New Venom-Based Clotting Assay of Protein C, ILJH 2007, corroborated our findings.
- We haven’t done any studies related to the effect of the prothrombin gene mutation, so there’s no way to be definitive, but, in theory, the excess thrombin in circulation could potentially be causing a procoagulant effect in-vitro that might be interfering with the assay (shortening clotting times) that might result in lower PC activity results. I’d be curious to know what her protein C antigen level is, if you have that data.
From George: I’m wondering if the mild prothrombin activity elevation associated with the prothrombin gene mutation is enough to account for a decreased Clot C. Given the physiology, I’d first look to the factor V Leiden mutation gene, however Dean’s documented information empirically rules out an effect related to protein C resistance. Of course, just the fact that the patient is pregnant could account for the reduced protein C, independent of factor VIII activity levels.