Factor V Leiden is a genetic disorder in which patients have an increased tendency to form thromboses, or blood clots. It’s pretty common in caucasians, as far as hereditary thrombotic disorders go: an estimated 5% of caucasians have the diseases in its heterozygous form (meaning that they have one normal factor V gene and one factor V Leiden gene). The disease is much less common in non-caucasian people.

The thing that’s abnormal about the product of the factor V Leiden gene is that although it can participate in clotting (factor V is one of the factors in the coagulation cascade), it can’t be turned off (normally a substance called protein C turns off factor V when it’s no longer needed). So once factor V Leiden starts, it can’t stop. The patient is therefore more likely to have abnormal, excessive clot formation.

Here’s an interesting pathology student question about laboratory testing for factor V Leiden disease.

Q. I dont understand why the INR (PT) would show up normal if a patient had factor V Leiden. If the level of factor V is high because protein C can’t cleave it, wont the INR (PT) be very low instead of normal because the clot forms quickly?

A. Good question! In factor V Leiden disease, the level of factor V is not high; it is normal. So clots form at the same rate that they would in a patient without factor V Leiden disease (remember: factor V Leiden is able to participate in the cascade just fine).

The problem in factor V Leiden disease is that factor V Leiden cannot be turned off. So at the point in time when factor V would normally be cleaved, factor V Leiden is not cleaved; it stays activated and continues to act on factor X and amplify the cascade.

If you put a patient with factor V Leiden next to a patient without factor V Leiden, and you activated both patients’ clotting cascades, they both would form fibrin at the same rate. Then, the patient without factor V Leiden would stop making clots, but the patient with factor V Leiden would continue to make clots.

Also – one kind of weird thing: coagulation tests (like PT/INR, PTT, TT) are either normal or prolonged (elevated). They are never shortened (decreased)! It’s not entirely clear why that is; perhaps there is no disease in which you are able to form fibrin at an increased rate. Anyway, these tests either tell you (1) you are making fibrin at a normal rate (in which case the test results will be normal), or (2) you are making fibrin at a slower-than-normal rate (in which case the test results will be prolonged, and you will probably be bleeding!).

Note: the lovely photo above of Leiden, South Holland, the town in which this disease was first described, was taken by Motumboe and can be found on Flickr at http://www.flickr.com/photos/motumboe/2709667509/