Factor V Leiden

Say you are chopping up peppers for your morning omelet and slip with the knife. Ouch! While cutting your finger seems to produce a huge amount of blood compared to the size of the wound, the actions going on behind the scenes to stop that blood flow are pretty darn cool.

When you get a cut or wound, a cascade of events takes place in the body.

Blood vessels are made up of endothelial cells (same type of cells that make up skin) which are tightly joined together. When a blood vessel gets damaged, it is imperative that the damage gets fixed quickly to prevent you from bleeding to death. The platelets in your blood clump together to form a clot to block the damaged part of the blood vessel. Platelets are flowing through your blood vessels all the time, though, without clumping together, so there has to be a way that they are activated to clump together when a clot is needed.

Collagen, which is located on the outside of the blood vessels, interacts with the platelets to cause them to clump together.  Another protein, fibrinogen, also come in to shore up the clot and make it strong by being activated into fibrin. There is a cascade of events that takes place here to quickly activate the fibrinogen. Thrombin is the main activator, turning fibrinogen into fibrin. Within this cascade of events are several other ‘factors’ that are integral to the process, including factor V (which we will focus on here) and factor VIII.

Factor V, coded for by the F5 gene, is a coagulation protein that is mainly synthesized in the liver.  It is activated in clotting by thrombin and can bind to activated platelets. Just as there is a cascade of events to quickly cause the blood clot to form, there are other molecules involved, such as protein C, in turning off the clotting when it is no longer needed. [ref]

Mutations (rare) that cause a deficiency in factor V cause mild forms of hemophilia, or an inability to clot well. More severe forms of hemophilia are caused by a mutation in other factor genes (e.g. factor IX mutation caused the type of hemophilia in European royal families).

The opposite problem is at play with the factor V Leiden variant. This is a change in the gene that causes a more active version that resists the shutoff signal from activated protein C and stays active, thus increasing thrombin and prolonging the clotting action. The clot can then become larger than it should be, blocking blood flow if it is in the wrong place.

Factor V Leiden has been linked in many studies to an increased risk of deep vein thrombosis and pulmonary embolism. A meta-analysis that combined the data from 31 studies estimates that the increase in the risk of thrombosis for people carrying one copy of the variant was 4-fold and the increase for those carrying two copies was 11-fold. [ref][ref][ref][ref]

This does not mean that everyone who carries the factor V Leiden will have a DVT or pulmonary embolism — just that they are at a statistically higher risk. The CDC estimates that the per year incidence of DVT is 1 to 2/1000 people. [ref] An 11-fold increase in risk for someone who is homozygous for the variant would then indicate a 1 to 2% risk of DVT in a given year.

Factor V Leiden has also been linked in studies to an increased risk of miscarriage. [ref][ref] The risk may be more for women who are homozygous for the variant. One study found that the rate of live births for non-carriers of factor V Leiden was 85%. Women who carrier one copy of the variant had an 84% live birth rate, and women who carried two copies of the variant had an 80% live birth rate.[ref]

A good source of information on thrombosis and clotting disorders is Clot Connect, from the University of North Carolina.

The factor V Leiden variant is found in about 5-8% of people of European descent. Researchers have several theories of why such a deleterious mutation has been passed down at a higher rate. One advantage of clotting more readily would be for women in childbirth, which historically included high rates of hemorrhaging. In times of war, it would also be an advantage to clot a little better when wounded. And finally, there is a statistically higher sperm count found in men who are a carrier of the factor V Leiden variant, so the mutation would have been slightly more likely to be passed on to more offspring.[ref][ref][ref]

Check your genetic data for rs6025 (23andMe v4, v5; AncestryDNA):

  • C/C: normal
  • C/T: one copy of factor V Leiden
  • T/T: two copies of factor V Leiden

Lifehacks:

Talk to Your Doctor:
This is one of those ‘talk to your doctor’ type of situations. Your doctor should know, based on all of your medical history, whether you should take preventative medications for thrombosis. Also keep in mind that 23andMe data is not guaranteed to be 100% accurate, so a clinical test should be done to verify the results before taking medical action.

The question that may come to mind here is whether talking with your doctor about carrying the genetic variant for factor V Leiden will raise your insurance rates.  In the US, your health insurance company cannot raise your rates due to the results of a genetic test. That is not true, though, for life insurance companies, who may (or may not) make their rate dependent on genetic information in your electronic health records. Here is more information on this topic from a genetic counselor: http://patientblog.clotconnect.org/2011/08/10/thrombophilia-and-insurance/

Activities:
Events that increase the risk for someone to have a blood clot include flying on airplanes and being dehydrated.  So drink lots of water and avoid alcohol and caffeine while flying

Aspirin:
There have been clinical trials on aspirin (100 mg/day) for preventing blood clots. The overall results show that there might be a minor benefit for women who carry the factor V Leiden variant — but again, talk with your doctor and see if this is right for you. [ref]

A 2006 study concluded that there is no reason for aspirin before flying on an airplane.[ref]

Cigarettes:
Smoking increases your risk for blood clots, and this would be magnified in someone with factor V Leiden.[ref]

The risk of blood clots for someone who is homozygous for the factor V Leiden variant, who smokes, is overweight, and is over age 60 is quite high. The absolute 10-year risk in this case for venous thromboembolism is 51%. [ref]

More to read:



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3 Comments on “Factor V Leiden

  1. Debbie: Well done. A most interesting item about Factor V Leiden

    Just to add a little:
    23andMe Raw data comes up with: rs6025 1 169519049 CC
    and
    ancestry.com Raw Data comes up with: rs6025 1 169519049 C C

    Some thousands of people have uploaded their RAW DATA files to: http://www.openSNP.org
    and
    https://www.opensnp.org/snps/rs6025#users shows the results for 1500+ people
    (this site is slow to load, try clicking on ‘other users’ and waiting until all 1500+ results appear).

    The results show 4% of the 1500+ are CT, and just 2 people are TT.

    ‘Factor V Leiden’ is fairly important – and being heterozygous is common at 4%.
    And certainly heterozygotes should be informing their physicians and surgeons.

    However it is the homozygotes with TT who should actively be taking precautions.

    There are other conditions that affect the risk of thrombosis and;
    Polycythemia Vera with its ‘JAK2 V617F’ mutation is much more severe;
    but fortunately much less common.
    There is more about PV on my website at: http://www.ianlogan.co.uk/pv-et/start.htm

    And, perhaps Debbie might write about this condition on this blog in due course.

    Ian
    (www.ianlogan.co.uk & ianlogan22@btinternet.com)

    • Hi Ian,

      Thanks for reading and commenting on the factor V Leiden article. Yes, about 4% or so of some population groups are heterozygous, thus the importance of getting the word out for people to check for this!

      I appreciate your suggestion on the JAK2 mutation, but I tend to stay away from writing about cancer-causing mutations on here. Especially for this one since JAK2 is a somatic mutation and 23andMe is not FDA approved on reporting on it. I’ll leave your link so that everyone can go to your site to read more about it…
      Debbie

      • Thanks fro the response, but everything is not quite as straightforward as it first looks.

        So … the ‘JAK2 V617F’ mutation does not in itself cause cancer, and that should not stop you writing about it.

        And, the mutation cannot be treated like the ordinary SNP mutations, so 23andMe testing, or that from any other direct-to-customer company, is of no use; as this mutation is only found in a cells of a ‘clone’ special testing techniques are required.

        So if people want to look at something a bit different, consider looking at the strange biology of the mutation ‘JAK2 V617F’.

        Ian

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