Factor V Leiden

Q. Could you please explain why the INR and PTT are not affected by the factor V Leiden mutation?

A. This is a GREAT question, and one that seems to come up every year when we do coag in our medical school. It seems like if a patient has a problem with factor V (as is the case in factor V Leiden), then the INR and PTT should be abnormal, since they both measure factor V (in addition to factors X, II and I). However, in factor V Leiden, the INR and PTT are normal! Why is that?

In factor V Leiden, patients have a point mutation in the factor V gene that produces a mutated factor V (it’s called factor V Leiden because this mutation was first described in Leiden, Netherlands). It turns out that this mutated factor V participates just fine in the coagulation cascade. The problem is that it can’t be turned off by protein C! The mutation in factor V Leiden just happens to be in one of the sites where protein C cleaves (and therefore inactivates) factor V; so in factor V Leiden, cleavage at that site doesn’t happen, and factor V “lasts” longer. So the mutated factor V just keeps working, even when the body is sending signals to stop making fibrin.

Back to the lab tests. The INR and PTT are normal in factor V Leiden because the patient with factor V Leiden makes fibrin at the same rate as a person with normal factor V. It’s just that later on, when the body tries to turn factor V off, the factor V Leiden patient will keep on making fibrin. Neither the INR nor the PTT measure this; in fact, no routine coag test measures it (they all just measure the time it takes to make fibrin).

So to diagnose factor V Leiden, you have to do genetic testing, which is fortunately relatively easy and cheap.