What is Factor V Leiden Mutation?
Factor V Leiden is a slight genetic change in a blood clotting factor called factor V. This alteration results in factor V being resistant to being broken down in the body. This condition increases the chances of developing blood clots, especially in individuals who have two copies of this mutation (homozygous) or seemingly two copies (pseudo-homozygous).
However, it’s crucial to note that many people with this mutation may never experience a blood clotting incident, known as a venous thrombotic event (VTE). Therefore, deciding on the best ways to prevent VTE, either as a first occurrence or as a repeated event, requires careful medical judgement. This is because, despite carrying the mutation, most people will never experience a VTE.
What Causes Factor V Leiden Mutation?
Your liver primarily produces something called factor V, which plays a significant role in blood clotting. In a normal body, a protein called thrombin activates factor V, which then turns prothrombin, another protein, into more thrombin. However, factor V is broken down by activated protein C, which helps stop the blood from clotting too much. Thrombin can actually help decrease clotting by activating protein C. Therefore, the amount and action of protein C are important in controlling how much thrombin is produced.
Factor V Leiden is caused by a genetic mutation that can be passed down from parent to child. It is important to note that just because you have the mutation, doesn’t mean you’ll definitely develop the disease.
Factor V Leiden happens because of a single change in the factor V gene. This change replaces one amino acid for another, eliminating one particular site for activated protein C on Factor V and Va. As a result, activated protein C, which normally stops factor V, can’t attach and deactivate factor V due to a mutation in the binding site. This means factor V remains active and raises the risk of developing blood clots.
Risk Factors and Frequency for Factor V Leiden Mutation
In simple terms, having one copy of the factor V Leiden mutation (which is a genetic difference) is the most common inherited blood clotting disorder in the White population. The percentage of people who have this condition is approximately 1% to 5%. Of individuals who experience a disease called venous thromboembolism (a condition where blood clots break loose and block blood vessels), about 10% to 20% have this mutation.
- Having a single copy of the factor V Leiden mutation raises the risk of developing blood clots about seven times.
- In the rare cases where a person has two copies of this mutation, the risk goes up about twenty times.
- Even though the risk for venous thromboembolism increases, there is no evidence to suggest that having one copy of this mutation increases overall chances of death.
Signs and Symptoms of Factor V Leiden Mutation
The factor V Leiden mutation primarily manifests as an increased risk for blood clots, otherwise known as venous thromboembolism (VTE). However, it’s important to note that most individuals with factor V Leiden will not develop VTE but may exhibit abnormal laboratory test results. Only a small percentage – about 5% of the general population and up to 20% of individuals in families prone to blood clots – will experience VTE due to this mutation.
VENOUS THROMBOEMBOLISM (VTE):
- VTE typically occurs as a deep vein thrombosis (DVT) or a pulmonary embolism (PE). Other uncommon sites can include the superficial veins of the legs or cerebral, portal, and hepatic veins.
- Isolated PE, without DVT, tends to be less common in people with factor V Leiden compared to those without it. This is known as the factor V Leiden paradox.
- Factor V Leiden mutation can also cause brain vein thrombosis, particularly in individuals taking oral contraceptive pills. Research indicates an increased risk of Budd-Chiari syndrome, a condition involving clotting in the liver’s veins, with this mutation.
ARTERIAL THROMBOEMBOLISM:
- The link between factor V Leiden and arterial thromboembolism, or clotting in the arteries, is under debate.
- There’s a small but noticeable increased risk of heart disease and stroke, particularly amongst women, smokers, and the young, with factor V Leiden.
PREGNANCY AND POSTPARTUM THROMBOEMBOLISM RISK:
- Thromboembolism affects about 1.2 of every 1000 deliveries, leading to significant illness and death. Further, factor V Leiden isn’t linked to repeated pregnancy loss or adverse pregnancy outcomes.
- Women with factor V Leiden, irrespective of their family history of clotting disorders, have a heightened risk of developing VTE and related complications during pregnancy.
Testing for Factor V Leiden Mutation
The American Society of Hematology (ASH) advises against routine testing for blood clotting disorders (thrombophilia conditions) in patients who have had their first occurrence of deep vein thrombosis (DVT) or pulmonary embolism (PE). This is because these tests can be expensive and don’t typically provide useful clinical information.
However, testing for a condition called Factor V Leiden is recommended in certain situations, especially for people who have suffered from venous thromboembolism (VTE), which refers to blood clots in the vein. You might be tested for Factor V Leiden if:
* You’ve experienced VTE at a young age, usually below 50
* You’ve had blood clots in unusual places, like veins in your ovaries, portal vein (which transports blood to your liver), or kidneys
* You’ve suffered from unexplainable arterial thrombosis
* You have a strong family history of thrombophilia
* You’ve developed VTE, despite taking blood-thinning medication
* You’ve had recurrent, unexplained cases of deep vein thrombosis/PE
If you are over 50 and have experienced your first episode of VTE or thrombosis, you are less likely to be tested.
Factor V Leiden can be diagnosed through genetic testing or a blood clotting test for Activated Protein C (APC) resistance. More specifically,
* Genetic testing is recommended if you have a family history of Factor V Leiden, if you are part of a family with a high rate of thrombophilia, if you have a condition called antiphospholipid syndrome, or if you need to take anticoagulants. If you have a positive result in the APC resistance test, you should also have a genetic test done.
* Mutation testing involves a technique called polymerase chain reaction, which detects the Factor V Leiden mutation. In this test, a unique enzyme would “cut” DNA from individuals who do not have the mutation; however, it will not cut the DNA in patients with the Factor V Leiden mutation. This results in a distinct pattern on a DNA gel.
* Functional APC resistance tests cost less than genetic tests. However, in rare cases, they may inaccurately indicate normal results in individuals on certain medications or those with a lupus anticoagulant disorder.
Treatment Options for Factor V Leiden Mutation
If you have a condition known as factor V Leiden mutation and develop venous thromboembolism (VTE), which is a blood clot in your veins, your treatment will be the same as someone without this mutation. Your doctor’s choice of blood thinner (anticoagulant) won’t be influenced by the presence of this mutation.
Anticoagulant selection depends on things like your preferences, your ability to stick with the treatment, how severe your blood clot is, and how this medication might interact with your other medicines.
Usually, drugs called direct oral anticoagulants (DOACs) are the first choice for typical VTE cases. If there’s worry about you sticking to the treatment, or if you have a severe pulmonary embolism (a blood clot in your lungs), your doctor might use a drug called warfarin. This medicine allows for more precise control over the blood’s ability to clot.
The length of time you’ll need to be treated for VTE doesn’t change if you have a factor V Leiden mutation. It’s based on your risk of getting another blood clot. In certain cases, like if your VTE is unexplained, threatens your life, occurs in a strange location, or happens more than once, you might need to stay on the anticoagulant indefinitely.
If you have two copies of the factor V Leiden mutation (you’re homozygous) and you’re getting surgery, your medical team will treat you as a high-risk patient. This means you’ll receive preventive blood thinning medications.
What else can Factor V Leiden Mutation be?
When checking for deep vein thrombosis (DVT), that’s a condition where a blood clot forms in the deep veins of your body, doctors might also need to rule out other conditions. They need to consider two main categories:
1. Inherited Thrombophilia: These are conditions that you might inherit genetically and can increase your risk of blood clots:
- Prothrombin G20210A mutation
- Protein S deficiency
- Protein C deficiency
- Antithrombin (AT) deficiency
2. Other Conditions: These include other diseases or factors that may increase your chance of having blood clots:
- Cancer
- Trauma or surgery
- Pregnancy or the use of birth control pills
- Long periods of no movement or being overweight
- Nephrotic syndrome, a kidney disorder causing your body to expel too much protein in the urine
- Antiphospholipid syndrome, when your body’s immune system attacks normal proteins in the blood
- Paroxysmal nocturnal hemoglobinuria, a rare disease resulting in the destruction of red blood cells
- Myeloproliferative disorders, conditions that cause your body to produce too many blood cells
- Heart failure
- Severe liver disease or cirrhosis
- Medications like tamoxifen, thalidomide, or lenalidomide
What to expect with Factor V Leiden Mutation
A certain number of people who have a condition known as factor V Leiden might experience a condition called venous thrombosis. This is a condition where blood clots form, often in the veins of the leg. Sometimes, these clots can travel to other parts of the body, like the lungs, leading to a serious and potentially deadly condition called thromboembolism, or more specifically, pulmonary embolism.
However, even though having factor V Leiden can raise your risk of developing a venous thromboembolism, current research hasn’t found any evidence that being a carrier of this condition (also known as being heterozygous) increases your overall risk of dying.
Preventing Factor V Leiden Mutation
Doctors encourage patients to focus on specific healthy lifestyle habits in order to improve their outlook for the future. This includes:
* Trying to maintain a healthy weight, and losing weight if needed.
* Eating a diet filled with healthy foods.
* Aiming to do at least 2.5 hours of exercise each week. Activities such as walking, swimming, cycling, running, playing tennis, or engaging in team sports are all recommended.
* Avoiding smoking as it can increase the risk of blood clots. Doctors can provide you with resources and medication to help quit smoking permanently.
