The Prothrombin 20210 mutation is found in about 2% of Caucasian people and is very rare in other populations. It is regarded as a very minor risk factor for DVT or PE and only increases the risk of thrombosis about 2 fold. This is less than the risk of taking an oral contraceptive and is similar to the risk associated with smoking. In fact some people believe it is a normal variant as the increased risk of thrombosis is so small.
What is the Prothrombin 20210 Mutation?
This is an abnormality in the gene for the clotting factor Prothrombin. It is a point mutation affecting the DNA sequence. DNA is made up of 4 different chemicals called nucleotides these are adenine, cytosine, guanine and thymine. The sequence of these nucleotides determines the structure of the protein. The nucleotides are usually represented by the letters A,C,G, and T. If the sequence changes then a different protein is produced. A change in one of these nucleotides is called a mutation. The prothrombin mutation is a change from guanine to adenine at position 20210 (g20210a) in the gene sequence . This mutation doesn’t actually alter the function of the protein but affects the production of the protein. When a protein is made DNA is copied to to a chemical called messenger RNA. This is then carried to a different part of the cell called a ribosome to make the protein. There is a region of DNA before the part that codes for the protein called the promoter region. The Prothrombin mutation is in the promoter region and affects the DNA processing leading to an increased amount of messenger RNA, which in turn leads to the production of more protein. Therefore people with the prothrombin mutation have more circulating prothrombin. The increased production of prothrombin tips the balance in favour of clotting very slightly.
What is my risk from this condition?
If you have the Prothrombin mutation your risk of a blood clot is about twice normal. For a young person it means that this risk remains very low at around 1 in 10,000 for somebody in their 20s. It is important to recognise that this is a minor risk factor. The risk has come from retrospective studies (looking at old data), there has been only 1 prospective study looking at the risk and this did not show the risk was significantly higher than normal. The reason I say you should be cautious putting too much weight on this finding is that some people who have had a blood clot are found to have this mutation. They then believe it is the cause of their problem. If other family members are tested and found not to have the mutation they feel reassured. However in many cases where this mutation has been found it is likely that other factors contribute to the risk of a clot. Therefore in practice I put more weight on the family history of clotting rather than this finding.
There is no evidence that this condition increases your risk of arterial thrombosis such as heart attack or stroke.
Can I take an oral contraceptive if I have this condition?
There does appear to be an increased risk of DVT and PE in women who have this mutation and take the oral contraceptive. It is approximately 15 fold higher than people without the mutation from most series. However it is hard to assess the risk as it has been derived from studies on women who have had a clot. The risk of a DVT and PE is less than reported with the factor V Leiden mutation. There is little evidence that screening all women for this mutation before taking the oral contraceptive is beneficial. The women at most risk are those with a family history. Therefore my advice is that women who have had a blood clot or who have a strong family history of blood clots (especially if a parent or sibling has had a clot), should not use an oestrogen containing contraceptive.
Can I take a progesterone only oral contraceptive?
The risk of thrombosis from a progestrone only oral contraceptive is very low and can be used by women with the Prothrombin mutation. Also it is safe to use a Mirena intra-uterine device, these do contain some progesterone but only a very small amount is absorbed and there is thought to be no risk of thrombosis.