Factor V Leiden is a coagulation disorder common among Caucasians that is associated with an increased risk of thrombosis. A thrombus is a blood clot in the blood vessels. In addition to heparins, so-called coumarins are available for therapeutic prophylaxis.
What is factor V Leiden?
Factor V Leiden mutation or factor V Leiden is a genetic coagulation defect. The genetic disposition affects clotting factor V of the clotting cascade. Affected individuals suffer from a tendency to thrombosis and therefore form blood clots significantly more frequently than other people. Factor V deficiency is also the most common cause of APC resistance. A deficiency in blood clotting factor V was first discovered by Max-Hermann Hörder in 1955. At that time, he attributed the deficiency to the blood clotting factor V inhibitor. In 1993, Swedish physician Björn Dahlbäck first described the factor V Leiden mutation. Dahlbäck named the genetic predisposition to thrombosis after the city of Leiden, where he lived during his research in the field. The FVL mutation follows the autosomal dominant mode of inheritance. Even when only one parent carries the FVL mutation, offspring have a five- to 10-fold higher risk of developing thrombosis.
Causes
Factor V Leiden is based on a point mutation. The mutation affects the gene that codes for factor V in blood clotting, respectively. Factor V Leiden results from a point mutation in the gene encoding factor V (mutation F506Q or G169A). In Europe, about 2-15% of the population are heterozygous carriers of the FVL mutation. (Source: MVZ Dr. Eberhard und Partner Dortmund) Factor V is the precursor of co-factor Va, which is irreplaceable for blood clotting and supports factor Xa in thrombin formation. Factor V is activated by thrombin and factor Xa via a positive feedback mechanism and inhibited by the protein C/protein S system. When factor V mutates, it cannot be cleaved and inactivated by the activated protein C. This is why the coagulation process proceeds as planned. For this reason, the coagulation cascade of patients runs with increased activity and the risk of blood clots increases. In Europe, five percent of the population are heterozygous carriers of the mutation. Only 0.5 percent of patients are homozygous carriers with mutations in both parents. The factor V Leiden mutation exists exclusively among Caucasians, but not among other ethnic groups.
Symptoms, complaints, and signs
Factor V Leiden carriers are affected by thrombotic tendencies. In medicine, thrombosis is a vascular disease in which blood clots form in blood vessels. In principle, all vessels can be affected by thrombi, although blood clots are far more common in the veins. The most common thrombosis, for example, is in the deep veins of the legs, which is a frequent complication, especially during pregnancy. People with factor V Leiden can also develop thrombosis in the arteries. Somewhat less frequently affected are the sinus veins in the brain. Blood clots in the sinus veins are referred to as sinus vein thrombosis. Superficial venous thrombosis presents clinically with a different picture than blood clots of the deep veins. Often, clot formation in superficial veins is associated with inflammatory components. The most common symptoms of thrombosis include swelling and feelings of warmth or tightness. The skin may become red or even blue in color. Many thromboses remain asymptomatic. However, it is symptomless clots that can subsequently cause engorgement, such as in pulmonary embolism, the most common complication of thrombosis.
Diagnosis
Factor V Leiden mutation can be diagnosed using functional testing and molecular genetics. In functional testing, the mutation appears as a prolongation of clotting time. In molecular testing, on the other hand, the laboratory detects the causative point mutation in the DNA. In addition, the analysis classifies the patient into the heterozygous or homozygous form. This differentiation is all-important. The two forms are associated with a clearly different risk of thrombosis. Therefore, different treatment guidelines apply to the forms. If a close relative is affected by thrombosis, testing for Factor V Leiden may be considered.Analysis may also be indicated in patients with repeated miscarriages of unclear cause or intrauterine growth retardation. The prognosis depends on the time of diagnosis. Factor V Leiden is now easily treatable. However, if prophylaxis is omitted because of lack of knowledge, an unfavorable to fatal prognosis may apply.
When should you see a doctor?
If signs of thrombosis – swelling, warm sensations, or a blue discoloration of the skin – are noticed, a visit to the doctor is recommended. Factor V Leiden is a serious condition that must be clarified and treated quickly to rule out complications. If symptoms occur, the patient must see a physician or go to a clinic on the same day. A pulmonary embolism must be treated immediately by a doctor. If chest pain, shortness of breath and palpitations suddenly occur, this indicates a serious condition and an emergency physician should be alerted. The affected person must be treated in a hospital in any case. If homozygous Factor V Leiden has been diagnosed, a doctor should be consulted regularly so that any thromboses can be detected at an early stage. In the event of unusual symptoms or signs of a new blood clot, it is best to call the emergency services or take the patient to the nearest hospital. If people in the family circle have been affected by thrombosis or even factor V Leiden, a preventive examination with regard to the clotting disorder is advisable.
Treatment and therapy
Factor V Leiden mutation cannot be treated causally. Symptomatic therapy is available. Treatment of factor V Leiden is required in only two situations. In acute thrombosis and in certain high-risk situations, therapy should occur. In this context, we are talking about thromboprophylaxis. For the treatment of acute thrombosis, heparins and vitamin K antagonists such as coumarins are mainly given. Heparins dissolve blood clots and inhibit blood coagulation. Coumarins curb the production of vitamin K, which plays a crucial role in blood clotting. Vitamin K is essential for the formation of clotting factors, so that by curbing it with coumarins, the clotting factors are only formed in small quantities. In this way, the substances reduce blood clotting. The anticoagulant treatment lasts about six months. Patients with homozygous factor V Leiden require longer therapy, as their risk of thrombosis is higher. Permanent thromboprophylaxis is given with vitamin K antagonists in tablet form.
Outlook and prognosis
The prognosis in factor V Leiden depends on many different factors. For example, the affected person’s lifestyle is primarily involved in the likelihood of developing a thrombosis. A healthy lifestyle and exercise reduce the risk. Smoking and being overweight, on the other hand, increase the risk immensely. Nevertheless, even in people who behave in an exemplary manner (from a medical point of view), thrombosis will occasionally occur. Whether or not it becomes a danger for the affected person depends on the time of detection. The better the formation of possible thromboses is kept in view and treated, the lower the risk of a dangerous incident caused by the thrombosis. Moreover, most thromboses can be dissolved without any problems. In addition, it is also relevant whether the factor V Leiden is heterozygous or homozygous: While the former only increases the tendency to thrombosis tenfold, the latter increases it a hundredfold. Accordingly, persons with homozygous factor V Leiden must be even more attentive to their bodies. In addition, affected women should not use the classic contraceptive pill, as this increases the risk of thrombosis in combination with the factor V Leiden mutation. Since there is no causal cure for the disease, affected individuals must deal with it throughout their lives.
Prevention
Factor V Leiden is a genetic defect. Therefore, the clotting disorder cannot be actively prevented to date. Molecular genetic analysis of blood clotting factors can at least be understood as a preventive measure for serious consequences of the mutation. If the analysis reveals factor V Leiden, thrombi can be prevented by prophylactic therapy, if necessary.
Follow-up
In factor V Leiden, there are usually no special aftercare options available to the affected individual.In most cases, the disease cannot be completely treated, so that patients are usually dependent on lifelong treatment. Self-cure does not occur. In general, the support and care of those affected by the family and close friends has a positive effect on the course of the disease. In particular, psychological upsets or depression can be prevented. In many cases, intensive discussions with close friends are necessary. Contact with other people affected by Factor V Leiden can also be very useful. The treatment of Factor V Leiden itself is usually carried out with the help of medication. Care must be taken to ensure that the medication is taken correctly and regularly, and attention must also be paid to possible interactions with other medications. Since the risk of thrombosis is also significantly increased by Factor V Leiden, regular examinations by a physician should be performed to prevent it. In general, a healthy lifestyle also has a positive effect on the course of this disease, and a healthy diet is also necessary.
This is what you can do yourself
No self-treatment is possible for factor V Leiden. Patients are always dependent on treatment by a physician in order to avoid further complaints. As a rule, however, taking vitamin K has a positive effect on the disease. However, those affected are also dependent on taking blood-clotting agents to alleviate the symptoms of Factor V Leiden. Early diagnosis and treatment are important in this disease. The earlier the disease is detected, the greater the likelihood of a positive outcome. Should a pulmonary embolism occur as a result of Factor V Leiden, a doctor should be consulted immediately. In acute emergencies, an emergency physician may also be called. In some cases, discoloration of the skin can be alleviated by cold applications. If the Factor V condition leads to psychological discomfort, support for the patient from friends and relatives can be helpful. Contact with other patients can also have a positive effect on the course of the disease. Since the disease also promotes the formation of thromboses, the affected person is dependent on regular examinations by a physician.
