Thrombophilie by change of the factor V

The thrombophilie by change of the factor V is most frequent of the Thrombophilie S. the frequency of this specific Mutation, with the state hétérozygote, in the European population in fact a question of current practice. It was identified in 1994 with Leyde (Netherlands) by Professors R. Bertina and Al

Other names of the disease

  • Change of Leiden

  • Change of the factor V of Leiden
  • Change of the factor V of Leiden with resistance to the protein C activated

Etiology

  • Mutation of the Gène F5 located on the Locus q23 of the Chromosome 1
  • the change consists of a substitution for the level of the Nucléotide 1691 of a Guanine by a Adénine of gene of the factor V involves the synthesis of a factor (Facteur V Leiden) resistant to the inactivation by the Protéine C activée.
Thrombin converts the factor V into its active form, which is inactivated by the activated protein C.

Incidence

The Prévalence varies considerably according to the populations.
  • the most rate is in the white population since 5 to 8% of this population would be Hétérozygote for this change with considerable variations according to the countries (10 to 15% of hétérozygotes in Sweden, 2 to 3% in Greece) the prevalence of the Homozygote S is of 1/5000.
  • the change is very rare in the black, Asian populations and the Australian aboriginals.

Description

This affection involves a coagulation faster Sang, which causes clots being able to lead to thrombo-embolic diseases by venous thrombosis or arterial.

Diagnosis

Private clinic

No clinical characteristic makes it possible to evoke the diagnosis of thrombophilie per change of the factor V. the conference of consensus of 2001 of the American college of clinical genetics recommends the research of the change in the cases below:
  • thrombo-embolic Disease before 50 years
  • a venous Thrombosis without particular context at any age
  • recurring thrombo-embolic Disease
  • venous Thrombosis of unusual site (cerebral, hepatic, mesenteric etc)
  • thrombo-embolic Disease during the pregnancy, the postpartum
  • thrombo-embolic Disease under oral contraception or substitute hormonal treatment
  • the first thrombosis with important family antecedents of thrombo-embolic disease (the definition of importance was not made).

The other demonstrations below can also taken into account:

  • unexplained fetal Loss of the second or third quarters
  • complicated Pregnancy of retro-placental and intra-uterine delay of growth
  • Thrombosis among women taking of the Tamoxifène or a selective Modulating of the receivers to the estrogens
  • Woman of month 50 years, smoky pre-eclampsia, hématome and doing to a Myocardial infarction
  • Anybody of more than 50 years making a thrombosis in the absence of cancer or of vascular prosthesis
  • Femme which one of the family members is carrying the change and who wishes to take an oral contraception or to be pregnant
  • Membre of a family with a known change.

The research of the change should not be made for:

  • Tracking of the population
  • Before a pregnancy or the catch of oral contraception or of a selective modulator of the receivers to the estrogens
  • Systematically in front of a thrombosis artérielle*

Biological

  • Screening test:
It is a phenotypical test which with the same sensitivity and specificity that the genetic diagnosis. The functional test evaluating resistance to the protein C activated (Resistance APC) makes it possible to detect more than 90% of the changes. But there exist some limits in its interpretation and it does not make it possible to differentiate in a reliable way the subjects hétérozygotes of the homozygotes.

Genetics

In France, it is obligatory to inform the patient of the realization of this test on the DNA genomic, and to conform in these circumstances to the legislation in force.
La research of the change by substitution of the Adénine by the Guanine on the level of the nucleotide 1691 of the F5 gene is positive in 100% of the cases.
Le the simplest test which can be fact is the use of the enzyme of MnlI restriction. The change is in the middle of a site of cut of the enzyme, and thus a simple PCR, a treatment of the DNA with MnlI, then an electrophoresis provides a fast diagnosic.
On can also use the Courbe of fusion in PCR in real-time. The presence of two different peaks show the presence or not change.

differential Diagnosis

  • In front of an increase in resistance to the protein C activated:
  • others trombophilies:
    • See the article thrombophilie

Assumption of responsibility of a person carrying a change

Systematic evaluation of the other causes of thrombophilies

Thrombosis

Prophylactic treatment

Pregnancy

Mode of transmission

  • dominant autosomic Transmission for the hétérozygotes
  • recessive autosomic Transmission for the homozygotes

The genetic Council

Sources

  • Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, MANDELEVIUM. MIM Number: 188055 * GeneTests: Medical Genetics Information Resource (database online). Copyright, University off Washington, Seattle. 1993-2005

Random links:Diaphragm (photography) | Geography of Aquitaine | Kfar-Haïm | Claude Schnitzler | ZRS | Gussie_Mueller