Prothrombin gene mutation (factor II, prothrombin 20210): what it means and how it is managed

Prothrombin is one of the blood-clotting factors. Thrombosis UK explains that it circulates in the blood and, when activated, is converted to thrombin, which makes fibrinogen turn into the fibrin strands that form the main part of a clot. The condition known as prothrombin 20210 is due to a mutation of the prothrombin gene. People who have it tend to have slightly stickier blood because they have higher prothrombin levels.

It belongs to a group of conditions called thrombophilia. The NHS describes thrombophilia as a condition where your blood clots more easily, and says it can usually be treated with medicines that help prevent blood clots. The NHS distinguishes inherited thrombophilia, caused by altered genes you are born with, from acquired thrombophilia that develops later because of another condition such as antiphospholipid syndrome or a liver or kidney problem. The prothrombin mutation is inherited.

Thrombosis UK notes that factor V Leiden and prothrombin 20210 are the most common thrombophilias among people of European origin, and that because inherited thrombophilias are genetic, how common they are varies between ethnic backgrounds.

Thrombosis UK says that if you have prothrombin 20210 you have a low risk of venous thrombosis unless you have one or more extra risk factors. The risk is about twice that of someone without the condition, but this risk is relatively low and most people with the condition are not affected. If you have prothrombin 20210 as well as factor V Leiden or protein S deficiency, the risk of thrombosis is substantially increased.

The NHS lists situations that raise the chance of a deep vein thrombosis (DVT) in anyone: being over 60, living with overweight or obesity, smoking, taking HRT or the combined contraceptive pill, cancer or heart failure, staying in or recently leaving hospital, surgery, being confined to bed for 3 days or more, long journeys of more than 4 hours, pregnancy and the 6 weeks after having a baby, and dehydration. For a person who carries the mutation these ordinary risk situations count for more, which is why they are worth knowing about.

Both Thrombosis UK and the NHS recommend practical steps: staying active, avoiding long periods without moving, keeping a healthy weight, not smoking, drinking enough fluid and getting medical advice before major surgery or prolonged immobility.

The mutation itself does not cause symptoms. The NHS says most people do not realise they have thrombophilia until it causes a blood clot. The symptoms are those of the clot: throbbing or cramping pain in one leg, usually the calf or thigh, swelling in one leg, and red, darkened or warm skin, or sudden difficulty breathing, chest pain and coughing up blood if the clot has reached the lungs.

The NHS advises asking for an urgent GP appointment or getting help from NHS 111 if you think you have a DVT, and calling 999 or going to A&E if you also feel short of breath or have chest pain, because the clot can travel to the lungs as a pulmonary embolism, which can be life-threatening and needs treatment straight away.

• One swollen, painful, warm or discoloured leg.

• Sudden shortness of breath.

• Chest or upper back pain, especially when breathing in.

• Coughing up blood.

• Fast heartbeat or feeling faint.

Thrombosis UK says that because it is common, prothrombin 20210 is usually included as part of standard thrombophilia testing. It is detected by a genetic test: a blood sample is taken and the DNA examined for the mutation in the prothrombin gene.

The NHS says you may be offered a blood test for thrombophilia if you had a blood clot and it is not obvious why, if a close family member has inherited thrombophilia, or if you have had 3 or more miscarriages. Testing is therefore generally targeted rather than offered to everyone.

Thrombosis UK states that if you have prothrombin 20210, it is not recommended in the UK that close blood relatives are tested because it is such a low-risk thrombophilia. Inherited thrombophilias are not usually tested for in children, who are usually tested only when they are old enough to understand why the sample is taken, usually after age 13, in conditions where testing is advised.

The NHS says there is currently no cure for inherited thrombophilia caused by altered genes. If your doctor thinks your overall risk of a blood clot is low you may not need any treatment. If you need treatment you will usually be offered anticoagulant medicine, which makes the blood less sticky and less likely to clot.

Most carriers never need long-term treatment. If a clot does happen, the NHS says DVT is treated with blood-thinning medicines, usually for at least 3 months, and a pulmonary embolism is treated with anticoagulant injections for at least 5 days and then tablets for at least 3 months. Whether to continue for longer after a clot depends on the circumstances and is decided by a specialist.

Contraception and hormone treatment deserve a conversation. Thrombosis UK advises women with inherited thrombophilia to seek medical advice if considering oral combined contraception, noting other forms are available, and says oral HRT increases clot risk whereas transdermal patches do not and are safe in those with inherited thrombophilia. The NHS says to tell your doctor about thrombophilia before medical procedures or new prescription medicines, including contraception.

Pregnancy raises clot risk in everyone, and the NHS says that if you are pregnant or planning a pregnancy you should contact your GP if you have thrombophilia, as you may need additional treatment and monitoring to reduce complications. Thrombosis UK says that if you have prothrombin 20210 and are pregnant, you should discuss this with your midwife.

Because it is inherited in an autosomal dominant way, each child of a carrier has a 50:50 chance of inheriting it, but inheriting it does not mean they will develop a clot.

Thrombophilia testing and advice are usually organised by a GP, haematology or obstetric services in the NHS, typically after a clot, a strong family history or recurrent pregnancy loss. Private haematology clinics offer similar testing, and the same guidance about who benefits from testing applies. Results are best interpreted by a clinician who knows your history.