Over the last few months we have been running a series of posts on the risk factors for thrombosis. A few weeks ago I looked at the link between family history and thrombosis and touched on inherited causes of blood clots. This is a big field and quite complex as more and more risk factors have been identified. In this post I will give you some background to the conditions called the “thrombophilias” and then look at each of the known inherited risk factors in more detail over the next few weeks.
Thrombophilia is a strange term and literally means “love of thrombosis” or “love of clots”. It is a term that has been adopted by doctors with an interest in blood clotting disorders to describe the inherited causes of blood clots. The first disorders were only identified in the 1960s and they have proved quite difficult to study. One big problem is that these inherited disorders do not always cause blood clots, in general they just increase the risk of somebody having a clot. So in a family where there is a history of blood clots it is not immediately obvious how the condition is inherited. The first inherited condition to be identified was the most series, a condition called antithrombin deficiency. Antithrombin is like an natural anticoagulant in the blood. If you have very low levels of antithrombin in your blood you have a high risk of blood clots. It was found in a family with a strong family history of blood clots. The next conditions to be identified were deficiencies of two other anticoagulants called Protein C and Protein S, again they were found through family studies and are regarded as relatively serious.
Over time scientists began to learn more about the way blood clots and through these studies found some mutations that affect the clotting proteins. Some of these are associated with an increased risk of blood clots. The word “associated” here is important as the link between these abnormalities and thrombosis came about through population studies looking for possible associations between the mutation and thrombosis. For example a mutation in the factor V gene, called factor V Leiden, is found in about 4% of the white Caucasian population. Most people with this mutation do not have blood clots, but if you look at the frequency of this mutation in people with blood clots it is significantly higher than in people without blood clots. This means there is an association between this mutation and blood clots, but it does not mean it is the cause of the clot.
In recent years research on the genetic causes of clotting has started to focus on the likelihood that multiple factors contribute to the risk of thrombosis; some are genetic and some are environmental. For example you may have a very strong family history of thrombosis; blood tests show you have the factor V leiden mutation, but there may be an additional mutation in your family that has not yet been identified. On top of that you are taking the oral contraceptive which is known to increase your risk of thrombosis, then you go on a long air-flight and have a DVT. Each of these risk factors on their own probably would not have given you a clot, but combined they all contribute to the risk.