Mutation factor V (Leiden mutation, resistance to protein C)

Mutation factor V has become the most common genetic cause of thrombophilia in the European population.

The factor V gene is located in chromosome 1, next to the antithrombin gene. Mutation of the gene leads to the fact that factor V replaces the amino acid arginine with glutamine at position 506. It is this point that serves as the site of action of activated protein C by factor V. Due to the replacement of amino acids, factor V does not activate protein C and as a result, there is no degradation of the factors Va and VIIIa, and this in turn leads to thrombosis.

Factor V mutation results in a lifetime risk of thrombosis, but at an older age than with a deficiency of antithrombin III and protein C and S. The risk of thrombosis in the resistance to protein C is extremely high. Among patients with this complication, the Leiden mutation is 25-40%. With this mutation, the risk of thrombosis is almost 8 times higher than without a mutation, and with homozygous carrier - almost 90 times.

Thrombosis often occurs in response to provoking factors, one of which is pregnancy.

According to M. Kupferminc et al. (1999), 25-50% of patients with placental abruption carry the gene of the Leiden mutation. Diagnosis of Factor V Leyden mutation is often carried out by determining the APTT without activated protein C and with it. If the APTT changes insignificantly with the addition of activated protein C, then we are dealing with resistance to activated protein C. However, in patients with similar obstetric complications, the APTT can be changed due to the presence of APS. Therefore, it is more rational to determine the mutation of the gene by PCR.

[1], [2], [3], [4], [5], [6], [7], [8]

Treatment of Factor V mutation (Leyden mutation, protein C resistance)

To date, there are no controlled, randomized trials of treatment efficacy in carriers of this mutation.

• Acute thrombosis in pregnancy - intravenous heparin at a dose of 10,000-15,000 units every 8-12 hours under the control of APTT, a course of 5-10 days, taking into account the severity of the condition, and then switch to low molecular weight heparin - dalteparin sodium at a dose of 5000-10 000 IU 2 times a day, supraparin calcium in a dose of 0.4-0.6 ml 2 times a day; Enoxaparin sodium in a dose of 40-60 mg 2 times a day.
• Complicated by thrombophilia during pregnancy and thromboembolic complications in the anamnesis - heparin sodium IV or low molecular weight heparin in smaller doses than with thromboembolic complications.
• In the absence of thromboembolic complications, but in the presence of mutation and thrombophilia - low-molecular-weight heparin in preventive doses throughout the pregnancy.
• After delivery, heparin sodium, then warfarin for 2-3 months after delivery, as this is the time of greatest risk of thromboembolism.