Factor V Leiden – A family affair

I see people with blood clots every week, and I am frequently asked,

“Why did I get a clot?”

Provoked or unprovoked clot

In many cases it is obvious why the clot occurred. In approximately 50% of cases, there is a clear provoking factor;

The common ones are.

In the other 50% the cause is not always so clear. Many of these people will have an inherited risk factor, and often it is a combination of factors that lead to a clot forming. When the cause is not obvious we call it an unprovoked clot. The risk of a second blood clot is higher if your first clot was unprovoked.

Inherited risk factors

Note I use the term “inherited risk factors” and not “inherited causes of thrombosis”. The distinction is important and will become more relevant in a later post.

Factor V Leiden is the commonest inherited risk factor. This is a condition found in people of European descent. It is found in about 4% of the population in Europe, North America and Australasia, but is much rarer in Asia and is virtually absent in indigenous populations in Africa. There is some evidence from genetic studies, that the factor V mutation occurred just once in the neolithic period with the original source in Turkey. That means everyone with this condition is related!

Factor V Leiden increases the risk of thrombosis about 6 fold. Therefore, if we look at people who have had a blood clot we will find 30% to 40% will have the factor V Leiden mutation.

The other inherited risk factors are:

• The prothrombin 20210 mutation – in 2% of the population
• Protein C deficiency – in 0.5% of the population
• Protein S deficiency – in 0.2% of Europeans and approximately 2% of Japanese
• Antithrombin deficiency – approximately 1 in 2000.

The precise number of people affected by these conditions is not known. These figures are all approximations.

These conditions are all found more frequently in people who have had a blood clot as you can see in the pie chart.

There are probably other inherited causes not yet identified as there are some families with several members affected with venous thrombosis, but the cause of their problem has not been found.

Factor V Leiden – discovery

Factor V Leiden is by far the commonest of these disorders but was only identified in 1994. A Swedish physician, Bjorn Dahlback, identified an abnormality of protein C activity in a number of people with blood clots. The cause was later shown to be a mutation in the factor V gene. A group of scientists in Leiden in the Netherlands subsequently published these findings in the journal Nature in 1994. The mutation was named Factor V Leiden.

I went to a baseball match with Bjorn Dahlback in the early 1990s as we were both doing research at Oklahoma Medical Center at the time. Bjorn was working on Protein C, and I was working on a different clotting protein, but I have followed his work ever since.

This year my interest in Factor V Leiden took a different turn when I realised it affected two of my children and by implication affected me, as I have a history of blood clots.

It is slightly ironic that I have never been tested for the Factor V Leiden mutation especially as my research was looking at inherited causes of venous thrombosis. During my research I used my own blood for some experiments, and I was tested for all other known causes of thrombophilia, just not factor V Leiden!

With the family involved, I thought this was a good opportunity to review the topic of Factor V Leiden.

In the next few posts I will discuss the following:

• What is Factor V and how does it work?
• What controls Factor V?
• What is factor V Leiden?
• What does it mean for me?
• Factor V Leiden and the Pill
• Should we look for it?