Assessment of the role of hemostatic gene polymorphisms in the development of venous thrombosis and pulmonary embolism in the perioperative period in patients with malignant tumors of thoracoabdominal localization
Abstract
Background. Venous thrombosis is one of the most common complications among patients
suffering from cancer. Currently the leading role in the pathogenesis of venous
thromboembolism is given to the phenomenon of thrombophilia, which implies
a violation of the hemorheological properties of blood with the
development of thrombosis. These conditions can be either
genetically determined or acquired. However, the dependence of thrombotic
complications on genetic factors in operated cancer patients has not been
sufficiently studied.
Aim - to evaluate the role of polymorphisms of blood coagulation system genes
(F2, F5, F7, F13, FGB, ITGA2,
ITGB3, PAI-1) in the development of
venous thrombosis and pulmonary embolism in patients with malignant tumors
of thoracoabdominal localization.
Material and methods. The prospective study included 121 patients operated in the Oncology
Department of Surgical Methods of Treatment # 11 (Thoracic Oncology) of
Thoracoabdominal Department of the N.N. Blokhin NMRCO in 2018-2019. The
study group (n=40) consisted of
patients with venous thrombosis/pulmonary embolism in the perioperative
period. The control group (n=81) included
patients who had no severe concomitant cardiovascular pathology, including a
family history.
Results. In patients with malignant tumors of thoracoabdominal localization
undergoing venous thrombosis/pulmonary embolism compared to patients without
thrombotic complications there were statistically significant difference
in the frequency of carrying the heterozygous variant (GA) mutation in the F5 gene (coagulation factor V, Leiden factor) (х2=4,118, p=0,043),
the homozygous form (CC) mutation
in the ITGB3 gene (platelet receptor fibrinogen) (х2=4,118, p=0,043),
the overall frequency of mutations in the PAI-1 gene (plasminogen activator inhibitor) (х2=4,025, p=0,045),
homo- (TT) and heterozygous forms (CT) of the mutation, as well as the overall
frequency of genetic disorders in the ITGA2 (integrin alpha-2) gene (х2=6,977, p=0,009;
х2=9,081, p=0,003;
x2=19,6, p<0,001,
respectively). Association of procoagulant mutations in the genes F2 (coagulation factor II prothrombin), FGB (fibrinogen)
with venous thrombosis did not reach statistical significance. The study
also did not show a significant difference in the group of patients with
thrombotic complications and in the control group in terms of the
frequency of carrying polymorphisms G10976A of the F7 gene (coagulation factor VII) and G103T of the F13 gene (coagulation factor XIII) associated with hypocoagulant-type
blood clotting disorders.
Conclusion. Thus, according to the results of the molecular genetic study, a
statistically significant difference in the frequency of polymorphisms G1691A
of the F5 gene, C807T of the ITGA2 gene, and T1565C of the ITGB3 gene and 5G(-675)4G of the PAI-1 gene was determined in patients with thoracoabdominal tumors who
underwent venous thrombosis/pulmonary embolism, compared with patients
without thrombotic complications. The issue of prevention of thrombosis in
cancer patients who are carriers of procoagulant mutations in the genes of
the hemostatic system requires further study.
Keywords:gene polymorphism, hemostasis system, thrombophilia, molecular genetic diagnostics, thrombosis, thromboembolism
Funding. The study was conducted without sponsorship.
Conflict of interests. The authors declare that there is not conflict of
interests.
For citation: Korolyova A.A., Gerasimov S.S., Kononets P.V., Lyubchenko L.N. Assessment
of the role of hemostatic gene polymorphisms in the development of venous
thrombosis and pulmonary embolism in the perioperative period in
patients with malignant tumors of thoracoabdominal localization. Clinical
and Experimental Surgery. Petrovsky Journal. 2021; 9 (1): 55-62.
DOI: https://doi.org/10.33029/2308-1198-2021-9-1-55-62 (in Russian)
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