Factor V Leiden

The factor V Leiden mutation ( "Factor Five Leiden mutation "; FVL ) is the most common inherited risk factor for thrombosis ( thrombophilia ), in which the increased risk of a blood clot (thrombosis ) to suffer. FVL results from a point mutation in the gene for factor V, a protein that plays an important role in the blood coagulation.

The modified base triplet leads to the incorporation of the amino acid glutamine in place of arginine at position 506 of the protein. The resulting clotting factor will now factor V Leiden, FVL briefly mentioned. By the change in the protein sequence, produces the so -called APC resistance: Usually the factor V is degraded by proteolysis, and thereby rendered ineffective by the activated protein C (APC). The altered structure in the FVL degradation of factor V by APC is inhibited ( it is "resistant" ), and the factor V retains its procoagulant effect. This leads to an imbalance of anticoagulant and procoagulant factors, thereby reducing the tendency to develop thrombosis, increases ( thrombophilic ).

In Europe, about 5 % of the population are heterozygous carriers of the FVL mutation, 0.05-0.5 % are homozygous carriers who have ever inherited a mutated allele from the father and mother.

Diagnosis of FVL mutation

The point mutation in the Factor V gene of guanine (G) to adenine (A) at position 1691 can be detected by DNA - sequencing. However, since the method for the direct detection is very expensive, the mutation usually have a restriction fragment length polymorphism (RFLP ) is demonstrated.

For this purpose, the DNA of a patient's blood sample with a polymerase chain reaction ( PCR) amplified and cut into different lengths nucleic acid chains, the gene in question by a chemical reaction using a restriction enzyme ( MLA1 ). The length of the nucleic acid chains is then determined in a gel electrophoresis. Restriction fragments of PCR products carrying the FVL mutation, exhibit a different size distribution than those derived from healthy volunteers, as a recognition site for the restriction enzyme is removed by the mutation.

Indication for study

Persons who come into closer kinship circle - this includes grandparents, parents, siblings and children of their own - repeatedly unexplained thromboses have occurred, to a coagulation diagnostics can undergo. This includes, among other things, the investigation on the FVL mutation and APC resistance. If at a person even occurred one or more thromboembolic disease, a coagulation diagnostics is also recommended. This applies even more so when for the occurrence of thrombosis there is no established risk factors ( obesity, immobilization, such as after surgery or fractures, taking hormonal contraceptives, etc.). In recent years (so-called habitual abortion ), stillbirth otherwise unknown cause and was in patients with recurrent miscarriages in severe intrauterine growth retardation also found an association with maternal thrombophilia ( thrombophilia ), so that even in these cases, a coagulation study of the mother and, if appropriate, prophylaxis is appropriate.

Inheritance of FVL mutation

The FVL mutation is inherited as an autosomal dominant. This means that even people who inherit the FVL mutation from only one parent ( heterozygous ), already a 5 - to 10-fold increased risk have to suffer a thrombosis. 8 % of the population of Bavaria alone have the genetic defect on in this form. If both parents the FVL mutation to their child pass (homozygous ), this even has a 50 - to 100-fold increased risk of thrombosis, because in his blood is present exclusively in the APC -resistant Factor V.

Historical Aspects

A blood coagulation factor V deficiency was first discovered in 1955 by Max Hermann Horder and a blood clotting factor V inhibitor ( FVI ) is returned. In 1993, then the factor V Leiden mutation ( FVL ) was for the first time by the Swedish doctor Björn Dahlbäck described, which ultimately results in an increased tendency to blood clotting. Dahlbäck had in 1989 an unusual accumulation of venous thrombosis observed in a young man, even with other family members of the man thrombosis were already occurred. For detailed examination of blood samples of the family first had to be developed and refined methods of investigation. Finally, the detection of a point mutation in the coding able to coagulation factor V gene is located on chromosome 1. The mutation is a single nucleotide at position 1691 changed (adenine instead of guanine). Dahlbäck named this genetic alteration, as is common among genome researchers, after the place of its discovery - the Dutch city of Leiden - as the factor V Leiden mutation.