Factor V Leiden, also called APC resistance, causes a hereditary disease that interferes with blood clotting. This means that sufferers have a higher risk of getting thrombosis. We cause the disease by a genetic mutation in the blood coagulation factor V (five). Factor V Leiden therapy includes measures to prevent and treat thrombosis. Read all important information about Factor V Leiden here.
Factor V Leiden: description
Factor V Leiden (spoken: “factor five ailments”) refers to a mutation of the gene on which the blueprint for factor V (five) of the coagulation system can be found. The disease is named after the Dutch City of Leidenwhere it was first discovered.
Due to the Factor V Leiden mutation, it comes to the so-called APC resistance, Although Factor V Leiden is often used as a synonym for APC resistance. Actually, this actually only describes the genetic mutation, not the disease itself. Genetic modification leads to a tendency for the blood to clump up. This increases the risk of thrombosis (venous blood clots).
Doctors refer to a condition in which the risk of thrombosis is increased, generally as a so-called thrombophilia, APC resistance is the most common genetic thrombophilia in Europe. In Germany alone, the genetic mutation is generally present in about seven percent of the population.
However, the severity of the disease depends on whether both parents (homozygous) or only one parent (heterozygous) have passed on the altered gene. People with heterozygous factor V Leiden have about five to ten times the risk of thrombosis. If a defective gene is inherited from both parents, the risk of thrombosis is even increased by 50 to 100 times. However, this homozygous factor V Leiden mutation is much less common – affecting only 0.2 percent of the population.
Striking is that the APC resistance exclusively for people of European descent occurs. In the natives of Africa, Asia, the Americas and Australia, factor V Leiden does not occur. Researchers believe that gene modification in evolution may have been a survival advantage. Because in case of injuries, it can be helpful if the blood clots quickly, so a certain protection against the bleeding is offered. At the same time, life expectancy in people with factor V Leiden is usually not limited, which is why there was no disadvantage in evolution.
Factor V Leiden: Symptoms
Often, the APC resistance (factor V Leiden mutation) runs for a long time completely without discomfort. The disease is usually only discovered when it comes to a blood clot (thrombosis) due to the increased blood coagulability. These blood clots mainly affect the venous vessels, blood vessels that lead oxygenated blood to the heart.
Thrombosis most commonly occurs in the deep veins of the leg (= deep vein thrombosis, DVT). This results in a painfully swollen leg, which is also strikingly warm and dark red to purple colored. It becomes dangerous if the blood clot from the leg is transported further in the blood stream and reaches the lungs via the heart. There it can clog vessels in the lungs (pulmonary embolism). Pulmonary embolism is usually associated with pain and respiratory distress and can be acutely life threatening.
So far, there is insufficient evidence that Factor V Leiden also causes blood clots in arterial vessels. The APC resistance does not increase the frequency of blood clots in the coronary vessels (-> heart attack) and in the brain vessels (-> stroke). On the other hand, there are indications that miscarriages are more common in women with APC resistance.
Factor V Leiden: Causes and Risk Factors
The most common cause of APC resistance is the Factor V Leiden mutation. A mutation is generally understood as a change within a gene. This mutation is inherited dominant. That is, sufferers pass the defective gene in any case to their children.
Factor V Leiden mutation leads to excessive blood clotting
Blood clotting is a very complex process. The main component of blood clotting is the so-called coagulation factors. These are different proteins, which together ensure that the blood clumps. One of them is the factor V formed in the liver.
In the Factor V Leiden mutation, the structure of the affected protein is minimally altered due to the genetic misinformation. But this has consequences: Normally, the antagonist of factor V, the activated protein C prevents (APC), excessive blood clotting. Due to the slightly altered structure of the factor V, the APC can no longer inhibit the factor V. It is also said that factor V is “resistant”. Therefore, the disease is also referred to as “APC resistance”.
Risk factors for thrombosis
Thrombosis occurs spontaneously in factor V Leiden in about 60 percent of the cases, ie without further risk factors. In about 40 percent are probably other risk factors responsible for a thrombosis. These include the use of hormonal contraceptives (eg pill), pregnancy and childbirth, obesity, surgery and prolonged immobilization. By immobilization is meant that a human, for example, due to surgery can not move sufficiently. Even traveling, especially the prolonged stay in car, bus or plane can promote the formation of thrombosis.
Factor V Leiden: Examinations and Diagnosis
The right contact for suspected Factor V Leiden is a doctor who specializes in blood disorders (Haematologist). Most people look for this doctor, if a thrombosis has already occurred and is looking for the cause. Especially if the thrombosis occurred before the age of 45, it should always be checked whether an APC resistance was possibly the trigger for the thrombosis.
At the doctor’s appointment, the doctor will first ask you in a conversation (case history) some questions about the current symptoms and possible pre-existing conditions. Possible questions of the doctor could be:
- Have you had a blood clot (thrombosis)? If so, at which body site?
- Have you had multiple thromboses?
- Did someone in your relationship already have a thrombosis?
- Have you ever had a miscarriage?
- Do you take hormonal contraception drugs?
That a Factor V Leiden is a disorder of blood clotting is the blood test after the anamnesis interview, the first examination step. You measure the time that the blood needs for coagulation (clotting time). To clarify the APC resistance, one analyzes the clotting time after the addition of activated protein C. Normally it should prolong itself because the activated protein C inhibits the factor V and thus the blood coagulation in healthy humans. However, in factor V Leiden mutation, the addition of activated protein C does not change the clotting time.
If APC resistance could be determined by the blood test, then it must be checked if a factor V Leiden mutation is responsible for it. Because theoretically, other diseases can lead to APC resistance.
To clarify this, there is a genetic examination, It can be examined at the molecular biological level, whether the typical genetic defect (factor V Leiden mutation) exists or not. In addition, it can be accurately assessed how severe the genetic defect is, ie, whether both gene copies carry the defect or only one of the two gene copies have the gene defect. This distinction is important to better assess the risk of thrombosis and to better plan the therapy.
Factor V Leiden: treatment
Since APC resistance is a genetic disease due to a Factor V Leiden mutation, it has not been causally treated. In any case, Factor V Leiden therapy is only necessary in two situations: first, if there is an acute thrombosis and secondly, if thrombosis is at least likely in certain risk situations. Then a preventive treatment (thrombosis prophylaxis) is necessary.
An acute thrombosis is usually treated with heparins and so-called vitamin K antagonists (“coumarins”). Thereafter, the anticoagulant therapy lasts for at least six months. In a homozygous factor V Leiden treatment can be even longer, since the risk of thrombosis is also higher. For permanent thrombosis prophylaxis, the vitamin K antagonists are used because they are available in tablet form. The heparins, however, there are only as syringes, which is why a long-term use would be problematic with them.
This ingredient dissolves a blood clot and inhibits blood clotting. Heparin is injected under the skin (subcutaneously) or directly into the vein (intravenously), which is why this drug is especially suitable for short-term use. The administration of heparin is usually well tolerated. Side effects rarely include heparin-induced poverty of platelets (HIT 1 or HIT 2) and therefore increased bleeding. Pregnant women with Factor V Leiden are usually always heparinized as this drug is well tolerated and does not pose a risk to the unborn child.
Vitamin K antagonists (“coumarins”)
Vitamin K plays an important role in blood clotting, it is essential for the formation of coagulation factors. Vitamin K antagonists reduce the production of vitamin K. As a result, the coagulation factors are no longer formed in sufficient quantity, which prevents blood clotting. Doctors say the coumarins “dilute” the blood. Although this name is not scientifically correct, it does make it clear that the coagulability of these drugs is reduced.
As an undesirable drug effect, however, it can lead to heavy bleeding, because the blood clotting is virtually eliminated. This is particularly problematic for injuries. The correct dosage of vitamin K antagonists is based on regular blood tests, in which the so-called Quick value is determined (= thromboplastin time = TPZ). Meanwhile, however, so that the values of different laboratories can be better compared with each other, instead of the Quick value of INR (International Normalized Ratio). For thrombosis prophylaxis, the target value of the INR is 2.0-3.0. (Without blood dilution, the INR is 1.0). Cumarine should always be taken exactly as prescribed by the doctor due to the potentially serious side effects of overdose. During pregnancy, they must not be used, as they are teratogenic.
New oral anticoagulants
In addition, the so-called “new oral anticoagulants” (NOAC) have been available for several years. These include agents such as dabigatran and rivaroxaban. These medicines can be used instead of vitamin K antagonists. Which a doctor chooses depends on the individual situation, for example, which other illnesses still exist.
Factor V Leiden: Pregnancy
Factor V sufferers often wonder if the condition affects a possible pregnancy. Pregnancy generally increases the risk of thrombosis for all women through hormonal changes. In women with APC resistance, it is therefore further increased during pregnancy. This poses a risk to the mother as well as to the unborn child. Women with APC resistance increasingly suffer from spontaneous abortions (spontaneous abortions). But: with adequate thrombosis prophylaxis with heparin, a Factor V Leiden is not a fundamental obstacle to the desire to have a baby.
Whether thromboprophylaxis is used during pregnancy depends on how serious the factor V defect is: in women with heterozygous factor V Leiden thrombosis prophylaxis during pregnancy is only recommended if the woman has other risk factors for a thrombosis such as obesity or varicose veins. In pregnant women with homozygous factor V Leiden, thrombosis prophylaxis is generally carried out during the entire pregnancy and up to eight weeks after delivery.
Factor V Leiden: disease course and prognosis
The genetic defect can not be treated causally. Factor V Leiden significantly increases the risk of thrombosis in heterozygous factor V Leiden (five to tenfold) and in homozygous factor V Leiden (50-100 fold). However, if Factor V Leiden is recognized early enough, lifestyle adjustment can already significantly reduce the risk of thrombosis. A waiver of nicotine and possibly a weight reduction are helpful. Women with Factor V Leiden should consult the gynecologist about the alternatives to hormonal contraception. A healthy diet and exercise are also preventive against thrombosis. If a medical dilution of blood is initiated immediately when a thrombosis occurs, the prognosis is quite good. However, in people with Factor V Leiden such blood killers occur again and again.