Thrombophilia and factor V Leiden

Causes and who gets it

In inherited thrombophilia, a person is born with a change in a gene that controls clotting. The main types are:

• Factor V Leiden: The clotting protein factor V cannot be stopped well enough by activated protein C, the protein that normally puts the brakes on it. Between 3 and 8 percent of people of European descent carry one copy; about 1 in 5,000 people carry two copies.
• Prothrombin G20210A (factor II) change: Too much prothrombin is made in the blood. It is the second most common inherited type and is found in about 2 to 5 percent of people of European descent. One copy raises the risk of a clot to 2 to 5 times the average.
• Antithrombin, protein C and protein S deficiency: The proteins that keep clotting in balance are low or do not work properly. These are rare; compared with the common types, they are more likely to lead to a clot.

The most common cause of acquired thrombophilia is antiphospholipid syndrome (APS). In this autoimmune condition, the immune system mistakenly makes antibodies against fat molecules in cells called phospholipids. It is more common in women and in people who have another autoimmune disease such as lupus.

Inherited thrombophilia can be passed on to children. People who got factor V Leiden from both their mother and their father (who carry two copies) have a higher risk than those who carry one copy.

Symptoms

Symptoms appear when a clot forms, and they depend on where the clot is.

• Deep vein thrombosis (DVT, a clot in a deep vein of the leg or arm): Usually throbbing pain and swelling in one leg, in the calf or thigh; red, darkened or warm skin over the painful area; veins that become more visible.
• Pulmonary embolism (a clot that travels to the lung): Sudden shortness of breath, chest pain that gets worse when you breathe in, coughing up blood, fast heartbeat.
• In APS, clots can also form in arteries; this can lead to a stroke or a heart attack.

According to the CDC (the US Centers for Disease Control and Prevention), about half of people who have a DVT may have no symptoms. Repeated miscarriages can also be a sign of thrombophilia.

Diagnosis and tests

Thrombophilia testing is not done routinely for everyone. According to ASH, how much testing helps with treatment decisions is debated. NICE NG158, the national guideline in England, recommends this approach:

• Thrombophilia testing is not recommended after a clot caused by a clear trigger such as surgery, injury, long bed rest, pregnancy or hormone use.
• Testing for inherited thrombophilia is not recommended while you are taking blood-thinning (anticoagulant) treatment.
• After a clot that formed without an obvious cause, testing for antiphospholipid antibodies may be considered if stopping treatment is planned. If a first-degree relative has also had a clot, testing for inherited thrombophilia may also be considered.
• Routine testing is not recommended for first-degree relatives of someone with a history of clots and thrombophilia.

The 2023 ASH guideline also keeps testing limited. If there is a family history of clots and a high-risk type such as antithrombin, protein C or protein S deficiency is known in the family, testing may be useful for decisions about pregnancy or hormone use.

The tests are blood tests; some are genetic tests. Diagnosing APS requires two blood tests 3 months apart. Some results are affected by blood thinners and by a recent clot. That is why your doctor decides when to do the test.

Treatment approach

There is no cure for inherited thrombophilia; the aim is to prevent clots. In acquired thrombophilia, the condition sometimes improves if the underlying cause is treated.

Some people with thrombophilia never have a clot and may not need treatment. If your overall clot risk is low, your doctor may suggest monitoring and preventive measures. Otherwise, blood-thinning (anticoagulant) medicines that make it harder for the blood to clot are usually recommended.

If you have had a clot, how long treatment lasts is decided for you personally, based on whether the clot was linked to a trigger, your risk of another clot and your risk of bleeding. Your doctor will discuss this with you and take your preferences into account. Blood thinners can cause side effects such as serious bleeding. Do not stop or change the medicine on your own.

Everyday life and follow-up

If you have thrombophilia, the following are recommended to lower your clot risk:

• Stay active; avoid sitting still for long periods.
• If you are overweight, try to lose weight.
• Do not smoke.
• Drink enough water; do not drink a lot of alcohol, because it can cause fluid loss.

Tell your doctor about your thrombophilia before any surgery or medical procedure and before starting a new prescription medicine. Some medicines may not be suitable for you; procedures may need extra preventive treatment or monitoring. Birth control methods that contain estrogen and menopausal hormone therapy raise the risk of clots.

The more risk factors come together, the higher the chance of a clot; learn the symptoms of a clot.

Pregnancy, children and special situations

Pregnancy and the first 3 months after giving birth raise the risk of clots for everyone; during pregnancy this risk rises about five times. Inherited thrombophilia and a family history of clots add to this risk. If you are pregnant or planning a pregnancy, tell your doctor early about your thrombophilia; extra treatment and monitoring may be needed.

Most women who carry factor V Leiden have a normal pregnancy. According to MedlinePlus, this change slightly raises the risk of miscarriage: repeated miscarriage or loss of the baby in the second or third trimester of pregnancy is 2 to 3 times more likely. Its link with other problems such as preeclampsia (a serious high blood pressure condition in pregnancy) has not been confirmed. For the prothrombin change, too, the link with pregnancy problems is debated.

APS can lead to problems such as miscarriage, preeclampsia and premature birth. Even so, people with APS can have successful pregnancies. Testing may be recommended for people who have had three or more miscarriages.

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