An Explanation of Factor V, by Michael Wosnick

For Ruth, Sally and others who asked about the difference, here is a modified, repeat of a post I made some time ago... Hope this helps.

Factor V itself is a clotting factor, whose normal role is to help blood to clot when an appropriate trigger is present. However, like all steps in the complex clotting cascade, Factor V is subject to regulation to keep it under control so that clots don't form too easily or too quickly. The normal traffic cop is Activated Protein C (APC). Another helper traffic cop working with APC is Protein S.

Normally, APC interacts with Protein S, and together they make a combo whose job it is to slow down the Factor V so that it does not lead to excessive clotting. When the Factor V is aberrant, i.e. you have the FVL gene, the mechanism by which the APC/Protein S traffic cop slows down the FVL gene is broken. Hence the traffic cop is rendered somewhat less effective than it normally is, and the inhibition of clotting is not as efficient as normally and so you have a tendency to OVER- clot.

The fact that the FVL mutation makes the APC/Protein S regulation mechanism not so effective is why FVL is also commonly called APC Resistance.

However, you can see from this that APC resistance caused by having the FVL gene is only ONE route to over clotting, but you can also see that if you have a normal Factor V gene but too little Protein S, it can lead to the same thing, i.e., there is not enough Protein S to combine with the APC. Also, if you have a normal Factor V gene but an abnormal Protein C, it too can lead to the same end result - too much activity of Factor V and a tendency to over-clot.

The APC resistance assay, which is a coagulation test is fairly sensitive, but is therefore NOT 100% specific for FVL, since it could be positive due to any perturbation in the activity of APC, of which FVL is the leading cause, but not the only cause. There is also the possibility that the APC Resistance assay will be indeterminate if you have a border line level.

The more foolproof test is a DNA test for the FVL gene mutation itself. It is non-ambiguous, but will only tell you if you are carrying one or two FVL genes. It will not tell you about any other mutations.

Ruth, the test you cite, namely FVL-PCR is the DNA test. The PCR stands for Polymerase Chain Reaction which is the technique used to amplify the DNA so it can be tested.

The DNA test looks specifically for the tell-tale G1691A mutation which shows that in the FV gene at position 1691 an "A" occurs where a "G" is supposed to be. This changes an amino acid in the Factor V protein from a residue called Arginine to one called Glutamine, and is the cause of the APC resistance that the other test measures.

The DNA test is by far the more precise, but is narrower in scope.

Therefore for all common intents and purposes, people use the terms "APC-Resistance" and "FVL" interchangeably, but in fact they are not precisely the same thing. All FVL will be APC resistance, but not all APC resistance will be FVL.