Dr. Jeff Hersh: FVL upsets coagulation
Q: My husband had a blood clot in his leg last year and the doctor recommended the kids be tested for some condition having to do with “factor five.” At first my daughter did not want to be tested, but now she says she will. Can you tell me what this condition is?
A: Many of the systems in the human body maintain proper balance by having mechanisms that “turn on” certain pathways while at the same time having other mechanisms that “turn off” the same (or competing) pathways. This is true of the coagulation system, responsible for controlling the clotting of our blood. There are different proteins that tend to make the blood clot (pro-coagulants) counterbalanced by proteins that tend to reduce/dissolve the blood clots (anti-coagulants). Today’s discussion will focus on the pro-coagulant called factor V, a protein that plays a role in stimulating the production of thrombin (an enzyme that leads to clot formation).
Factor V Leiden (FVL) is a gene mutation that may upset the balance of the coagulation system by reducing the ability of activated protein C to cleave (inactivate) factor V (decreasing the anti-coagulant role protein C plays), as well as increasing the pro-coagulant role of activated factor V. Through both these mechanisms people with FVL have a propensity to have their blood form clots. In fact, FVL is the most common cause of inherited thrombophilia (the increased propensity to form blood clots).
Inheriting one copy of FVL mutation is very common, affecting up to 5 percent of Caucasian Americans, 2 percent of Hispanic Americans, 1 percent of African Americans and 0.5 percent of Asian Americans. Those with one copy of the mutated gene (inherited from only one parent) have a seven-fold increased risk of developing a blood clot, equating to a lifetime risk of one in 20; the large majority of people with FVL do not develop any problems. Having two copies of the FVL mutation increases the risk of developing a blood clot to 80-fold that of a non-affected person.
The fact that not everyone with FVL develops a blood clot speaks to the fact that there are many other things that modify the risk; not all of these modifiers are known or understood. One that is identified is that those with FVL who have non-O blood types (blood type A, B or AB) have a higher risk of developing a blood clot than those with O-type blood.
The blood clots in people with FVL occur in the veins, most commonly those in the legs but sometimes in other locations. The clots can be in the superficial veins, in which case the symptoms are usually warmth, tenderness and/or redness in the affected area. If the deep veins are affected (called deep vein thrombosis or DVT), there can be similar symptoms as with superficial clots but swelling distal to the clot may also occur.
If a piece of the blood clot breaks off and travels to the lungs (called a pulmonary embolism), the patient may develop shortness of breath, chest pain and/or rapid heart rate and could potentially die from this serious condition.
Testing for FVL involves a check of the overall coagulation pathway, with more specific testing looking for the specific gene mutation possibly being done as well.
The acute treatment of someone with a blood clot depends on the location of the clot and the symptoms. It may involve medicines to break apart the clot (thrombolysis) or medications to minimize further blood clots from forming. Oral medications to minimize blood clot formation (sometimes colloquially called “blood thinners”) may be prescribed.
People who have FVL and also other medical conditions, such as deficiencies of certain other proteins, cancer or other conditions, may be at an even higher risk of developing blood clots. When a woman with FVL gets pregnant she may also be at an increased risk of developing blood clots and even certain complications of her pregnancy. Situations that increase the risk of developing a blood clot, such as sitting with no movement during long car or plane trips, also may increase the risk.
Since FVL is an inherited condition, family members of someone diagnosed with it should consult their healthcare provider to see if they should be screened. Everyone should do certain things to minimize developing a DVT, such as quitting (or better yet never starting) smoking, doing exercises/moving around periodically during long car or plane trips and maintaining a healthy weight (obesity is also a risk factor for developing DVTs).
Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.