Background.Von Willebrand disease is a hereditary malfunction of the blood coagulation system caused by waveform quantitative and/or qualitative deficiency of von Willebrand factor (vWF).Aim.To evaluate the frequency of occurrence of FVLeiden and FII G20210A mutations in female patients with von Willebrand type 1 disease.Materials and methods.136 women aged from 18 to 45 years (mean 31.7 ± 0.5 years) were enrolled in a study conducted during the January 2011 — December 2017 period. Questionnaire was used to reveal hemorrhagic diathesis. Inclusion criteria were as follows: no less than 3 positive responses to questions 1–7, or 2 positive responses to questions 1–7 plus no less than 100 points of the evaluated menstrual blood loss. An independent inclusion criterion was 180 points or more in the question concerning menstrual blood loss. A mandatory inclusion criterion was the confirmation of absence of thromboembolic events in a proband and first line relatives. The study included assessment of such parameters as ristocetin-cofactor activity of von Willebrand factor (vWF:RCo), von Willebrand factor antigen (vWF:Ag), factor VIII (FVIII:C), platelet aggregation induced with ADP, ristomycin, collagen, as well as molecular-genetic assay of factor V (FVLeiden) and gene (FII G20210A) polymorphism using allele-specific polymerase chain reaction.Results.No mutations of FVLeiden and FII G20210A were revealed in 102 women with von Willebrand disease type 1. Heterozygous mutation of FVLeiden was found in 12 (8.8 %) subjects with von Willebrand disease type 1 (vWF:RCo from 27 to 47 % (mean 37.3 ± 0.8 %), vWF:Ag from 25 to 46 % (mean 37.5 ± 0.8 %), FVIII:C from 29 to 49 % (mean 44.1 ± 0.5 %). Homozygous mutation of FVLeiden was identified in 3 (2.2%) women with von Willebrand disease type 1, with vWF:RCo being 40, 43 and 45 %, vWF:Ag — 39, 44 and 42 %, FVIII:C — 47, 45 and 48 %, respectively. Heterozygous mutation FII G20210A was detected in 19 (13.9 %) subjects with von Willebrand disease type 1 (vWF:RCo from 36 to 49 % (mean 43.0 ± 0.4 %), vWF:Ag from 32 to 46 % (mean 42.2 ± 0.6 %), FVIII:C from 30 to 49 % (mean 45.1 ± 0.4 %).Conclusion.By means of diminishing the coagulation potential of the blood coagulation system, a decrease in the activity of VIII and von Willebrand factors may compensate possible negative effects associated with FVLeiden and FII G20210A gene mutations in female patients with von Willebrand type 1 disease.
Polymorphism in the promoter region of von Willebrand factor gene and von Willebrand disease type 1