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.
What is symptoms for V leiden disease?
Patients with factor V Leiden may have no symptoms at all – or they may have symptoms of abnormal blood clots. The symptoms depend on where the clot is; if it is in the lungs (which is called a pulmonary embolism), the patient would have chest pain and shortness of breath. Clots can occur anywhere in the body – so the potential symptoms are many.
Makes sense, thanks!
Thanks for the explanation!
Thank you.
Thats an excellent explanation. Makes sense
Thanks a thousand time you are a genius
Hi Dr. Krafts,
can you tell me what will be the INR , Pt and PTT in hypercoaguable disorders in general like
Prothrombin activating mutation , Anithrombin deficiency , Protein C and S deficiency. I think all will have normal values because we measure prolongation of time rather in all these values ?
I hope you can clarify this concept for me and if it is actually the same generalization for all then it will be very easy to attempt exam questions and later to examine blood profiles of patients .
Another beautiful & simple explanation! I came here after reading today’s path bite. Thanks so much!
Thanks for the nice explanation