Problems of Radiation Medicine and Radiobiology

О.Yu. Mishcheniuk¹, О.М. Kostiukevych¹, L.K. Benkovska¹, О.М. Kravchenko¹, S.V. Klymenko^2,3

¹State Institution of Sciences «Research and Practical Center of Preventive and Clinical Medicine», State
  Administrative Department, 5 Verkhnia St., Kyiv, 01014, Ukraine
²State Institution «National Research Center for Radiation Medicine of National Academy of Medical
  Sciences of Ukraine», 53 Yuriia Illienka St., Kyiv, 04050, Ukraine
³Shupyk National Medical Academy of Postgraduate Education, 9 Dorohozhytska St., Kyiv, 04112, Ukraine

CONTRIBUTION OF THE G1691A ALLELE CARRYING OF THE COAGULATION FACTOR V GENE TO THE DEVELOPMENT OF THROMBOSES IN EXPOSED PATIENTS WITH REACTIVE CHANGES IN PERIPHERAL BLOOD

Thrombosis triggers, in addition to «classic» risk factors (RFs) of cardiovascular events, includes the reactive changes of peripheral blood (RCPB), markers of the hereditary thrombophilia and radiation anamnesis. However, results of most studies suggest the «classic» RFs are able to neutralize the prothrombogenic potential of the hereditary thrombophilia and other, less powerful predictors of thrombosis.
Objective: to determine the influence of the G1691A allele of the proaccelerin gene carrying to the thrombosis development, taking into account the vascular type of their occurrence, the presence of RFs in individuals with RCPB (reactive leukocytosis and thrombocytosis, and secondary erythrocytosis), as well as with and without radiation anamnesis.
Material and methods. In general, it was analyzed the results of clinical and molecular-genetic data of 152 patients with RCPB, 19 patients had radiation anamnesis, 133 – did not have. The thrombotic complications were detected in 5 (26.31 %) of radiation-exposer patients and 25 (18.79 %) patients without radiation anamneses. The carrying of the G1691A allele proaccelerin gene (APG) (Leiden mutation (LM)) was detected using the allele-specific polymerase chain reaction.
Results. The LM was found in 5.9 % (9 carriers) of the general cohort (GC) of RPBC patients. There were no difference in the LM frequency between the groups of patients with and without radiation anamnesis (р = 0.312). In the group of radiation-exposer patients (р = 0.017), as well as in the group without its (р = 0.031), venous thromboses only were more frequently in the LM carriers. In the presence of a radiation anamnesis, G1691A APG carriers with RFs have the higher frequency (р = 0.008) and the probability of the occurrence (relative risk [RR] = 25.00; CI 95 %: 1.56–399.68) of venous thrombosis. In the group without radiation anamnesis, the frequency of venues thrombosis in the LM carriers is higher in the younger age subgroup (р = 0.001), without RFs (p = 0.044) and without RFs under 60 years (р = 0.023). The risk of venous thrombosis in the G1691A APG carriers of the group without radiation anamnesis is 5.78 (95 % CI: 1.58–21.13). In LM carriers without radiation anamnesis and RFs, as well as under the 60 years of age, the probability of venous thrombosis was 6.85 (95 % CI: 1.86–25.22) and 19.40 (95 % CI: 4.64–81.09), respectively, and in the absence of both criteria – 9.57 (95 % CI: 2.49–36.73).
Conclusions. In patients with and without radiation anamnesis, the risk of venues thrombosis are observed more often in carriers of LM. The carrying of the G1691A APG in patients with RPBC and without RA increased the risk of venues thrombosis development in subjects without FRs and below 60 years of age. In the radiation-exposure group, the frequency and the risk of venues thrombosis in the G1691A APG carriers was higher in the subgroup with RFs. It is probably due to the peculiarity of the samples, or prothrombogenic interaction between LM and radiation-associated endothelial damage.
Key words: reactive changes of peripheral blood, the G1691A allele of the coagulation factor V gene, risk factor of thrombosis.

Problems of Radiation Medicine and Radiobiology.
2020;25:502-515. doi: 10.33145/2304-8336-2020-25-502-515

full text

1. Adams MJ, Steven LE, Schwartz C, Fajardo LF, Coen V, Constine LS. Radiation associated cardiovascular disease: manifestations and management. Semin Radiat Oncol. 2003;13(3):346–356. doi: 10.1016/s1053-4296(03)00026-2.
2. Rutqvist LE. Novel approaches using radiation therapies. Recent Results Cancer Res. 1998;152:255–264. doi: 10.1007/978-3-642-45769-2_24.
3. Grau AJ, Boddy AW, Dukovic DA, Buggle F, Lichy C, Brandt T, et al. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke. 2004;35:1147–1152.
4. Khan PN, Nair RJ, Olivares J, Tingle LE, Li Z. Postsplenectomy reactive thrombocytosis. Proc (Bayl Univ Med Cent). 2009;22(1):9-12. doi: 10.1080/08998280.2009.11928458.
5. Nagaraju SP, Bairy M, Attur RP, Sambhaji CJ. Cerebral venous thrombosis and secondary polycythemia in a case of nephrotic syndrome. Saudi J Kidney Dis Transpl. 2016;27(2):391-394. doi: 10.4103/1319-2442.178575.
6. Spector EB, Grody WW, Matteson CJ, Palomaki GE, Bellissimo DB, Wolff DJ, et al. Technical standards and guidelines: venous thromboembolism (Factor V Leiden and prothrombin 20210G >A testing): a disease-specific supplement to the standards and guidelines for clinical genetics laboratories. Genet Med. 2005;7(6):444–453. doi: 10.1097/01.gim.0000172641.57755.3a.
7. Baglin T, Gray E, Greavegs M, Hunt BJ, Keeling D, Machin S, et al. British Committee for Standards in Haematology. Clinical guidelines for testin for heritable thrombophilia. Br J Haematol. 2010;149(2):209–220. doi: 10.1111/j.1365-2141.2009.08022.x. .
8. Walker ID, Greaves M, Preston F. Investigation and management of heritable thrombophilia. Br J Haematol. 2001;114(3):512–528. https://doi.org/10.1046/j.1365-2141.2001.02981.x
9. Franchini M, Lippi G. Factor V. Leiden and hemophilia. Thromb Res. 2010;125(2):119-123. doi: 10.1016/j.thromres.2009.11.003.
10. Segal JB, Brotman DJ, Necochea AJ, Emadi A, Samal L, Wilson LM, et al. Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review. JAMA. 2009;301(23):2472-2485. doi: 10.1001/jama.2009.853.
11. Mean M, Limacher A, Stalder O, Angelillo-Scherrer A, Alberio L, Fontana P, et al. Do factor V Leiden and prothrombin G20210A mutations predict recurrent venous thromboembolism in older patients? Am J Med. 2017;130(10):1220.e17-1220.e22. DOI: 10.1016/j.amjmed.2017.05.026.
12. Gupta N, Khan F, Tripathi M, Singh VP, Tewari S, Ramesh V, et al. Absence of factor V Leiden (G1691A) mutation, FII G20210A allele in coronary artery disease in North India. Indian J Med Sci. 2003;57(12):535-542.
13. Gandrille S, Alhenc-Gelas M, Aiach M. A rapid screening method for the factor V Arg506-->Gln mutation. Blood Coagul Fibrinolysis. 1995;6(3):245-248. doi: 10.1097/00001721-199505000-00008.
14. De Stefano V, Za T, Rossi E, Fiorini A, Ciminello A, Luzzi C, et al. Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia. Haematologica. 2009;94(5):733-737. doi: 10.3324/haematol.13869.