ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМПymj-1379Research ArticleСтатьиГенетические аспекты гемостаза у детей с артериальными ишемическими инсультамиGenetic Aspects of Hemostasis in Children with Arterial Ischemic StrokeМининК. И.MininA. V.

Минин Алексей Владимирович – ассистент кафедры психоневрологии 

Aleksey V. Minin: assistant, Psychoneurology department 

St. Petersburg, Litovskaya str., 2 

aleksey_minin@mail.ruПшеничнаяК. И.PshenichnayaK. I.

Пшеничная Ксения Ивановна – д.м.н., проф. 

Ksenia I. Pshenichnaya: M.D., professor  Pediatrics department 

St. Petersburg, Litovskaya str., 2 

kpshenichnaya@yandex.ruПальчикА. Б.PalchikA. B.

Пальчик Александр Бейнусович – д.м.н, проф. 

Alexander B. Palchik: M.D., neurologist, professor Psychoneurology departmen

St. Petersburg, Litovskaya str., 2 

xander57@mail.ruСанкт-Петербургский гос. педиатрический университетРоссияSt. Petersburg State Pediatric Medical UniversityRussian Federation201414092025022527Copyright © Минин К.И., Пшеничная К.И., Пальчик А.Б., 20252025Минин К.И., Пшеничная К.И., Пальчик А.Б.Minin A.V., Pshenichnaya K.I., Palchik A.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/1379

В условиях нейрохирургического отделения детской городской больницы (г. Санкт-Петербург) обследованы дети (мальчики и девочки) в возрасте от 6 месяцев до 17 лет, перенесшие артериальный ишемический инсульт (АИИ). У 3 детей и 17 родителей диагностированы различные нарушения гемостаза: медленное угасание синяков, носовые кровотечения, кровоизлияние в склеры, кровоточивость десен и др. Исследование генов-маркеров тромбофилии у обследованных детей показало, что редко встречаемые в популяции (1-4%) генотипы G/g и G/A протромбина G20210A выявлены у 50% обследованных больных.

In acute and recovery periods it is obligatory to detect blood diseases and pathological conditions leading to recurrent cerebral thrombosis. 

Aim of the study

Aim of the study. To define genetic factors influencing thrombogenesis in children with AIS.

Materials and methods

Materials and methods. At neurosurgical department of Children’s City Clinical Hospital named after N.F. Filatov (St. Petersburg) we observed 33 children with AIS (20 male and 13 female) aged from 6 months to 17 years old. The diagnose was based on the developed focal neurological symptoms, that were present more than 24 hours, and changes, characteristic for AIS [18, 4], on the KT and MRT images. During history taking hemostasis disorders were detected in children and their relatives. 18 children had molecular genetic investigation of 10 genes thrombophilia markers.

Results and discussion

Results and discussion. In the history evidence of hemostasis disorders was found in 3 children with AIS and included: easy development and slow disappearance of bruises, inadequacy of hematomas to pattern and severity of injury, prolonged nasal, sclerotic and gum bleeding (also after traumas and operations). Parents of children with AIS hadn’t suffered stroke, but their nearest relatives had different strokes – in 6 cases on the mother’s side, and in 8 cases on the father’s side. During history taking in some parents, mainly in mothers (15 cases), and in 2 fathers hemostasis disorders signs were detected, in the majority of cases – haemorrhagic. At data assessment of thrombophilia genes’ polymorphism (in 18 children) the occurrence frequency of mutant allele in the European population was considered. We determined the coefficient of ratio of gene mutation frequency in the study group (p%) to the mean figures in the general population (P%), and we may estimate the value of this polymorphism in the course of AIS in the study group. According to this ratio (p/P) prothrombin gene Prt (G20210A), MTHFR A1298C, fibrinogen FGB (G-455A), platelet receptor gene GP Ib and GP IIIa had the highest coefficient. The widespread cause of cerebral vessels’ thrombosis, factor V Leiden mutation, was not detected.

Conclusion

Conclusion. The obtained results demonstrate that during history taking in children with AIS and their parents it is important to detect not only thrombosis but also haemorrhagic disorders. Children with confirmed AIS need further molecular genetic study of thrombophilic markers to detect etiological factors, as all the examined children had heterozygous and homozygous mutant genes.

детиартериальный ишемический инсульттромбофилиягенетические маркерыchildrenarterial ischaemic strokethrombophiliagene markersReferencesАлексеев Н.А. Геморрагические диатезы и тромбофилии / Н.А. Алексеев. – СПб.: Гиппократ, 2005. – С. 516–556.Alekseev N.A. Haemorrhagic diathesis and thrombophilia / N.A. Alekseev. – SPb.: Gyppokrat, 2005. – Р. 516–556.Зыков В.П. Диагностика и лечение артериального ишемического инсульта у детей в остром периоде / В.П. Зыков, И.Б. Комарова, Л.В. Ушакова // Вопросы современной педиатрии. -2011. – №4. – С. 70-77.Zykov V.P. Diagnostics and treatment of an arterial ischemic stroke in children in acute period / V.P. Zykov, I.B. Komarova, L.B.Ushakova // Questions of modern pediatrics. -2011. – №4.– Р. 70-77.Пшеничная К.И. Геморрагический синдром у детей и подростков с маркерами наследственной тромбофилии / К.И. Пшеничная, Т.А. Мельникова, Е.В. Люгаев // Педиатрия. – 2009.– №4. – С. 64-68.Pshenichnaya K.I. Hemorrhagic syndrome in children and teenagers with markers of a hereditary trombofiliya / K.I. Pshenichnaya, T.A. Melnikova, E.V. Lugaev // Pediatry. -2009. – №4.– Р. 64-68.Arterial ischemic stroke in children / J.J. Gemmete, I. Davagnanam, A.K. Toma [et al.] // Neuroimaging Clin N Am. – 2013. – Vol. 23, №4. – Р. 781-98.Arterial ischemic stroke in children / J.J. Gemmete, I. Davagnanam, A.K. Toma [et al.] // Neuroimaging Clin N Am. – 2013. – Vol. 23, №4. – Р. 781-98.Clinical and radiological recurrence after chldhood arterial ischemic stroke / V. Ganesan, M. Prengler, A. Wade [et al.] // Circulation. 2006.– Vol. 114, №20. – Р. 2170-2177.Clinical and radiological recurrence after chldhood arterial ischemic stroke / V. Ganesan, M. Prengler, A. Wade [et al.] // Circulation. 2006.– Vol. 114, №20. – Р. 2170-2177. 6. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies / G.L. Kenet, L.K. Lьtkhoff, M. Albisetti [et al.] // Circulation. -2010.– Vol. 121, №16. – Р. 1838-47.Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies / G.L. Kenet, L.K. Lьtkhoff, M. Albisetti [et al.] // Circulation. -2010.– Vol. 121, №16. – Р. 1838-47.Inherited and acquired risk factors for arterial ischemic stroke in childhood / G. Lippi, M. Franchini, M. Montagnana [et al.] // J Thromb Thrombolysis. –2009. –Vol. 27, №2. –Р. 239-248.Inherited and acquired risk factors for arterial ischemic stroke in childhood / G. Lippi, M. Franchini, M. Montagnana [et al.] // J Thromb Thrombolysis. –2009. –Vol. 27, №2. –Р. 239-248.Jordan L. C. Challenges in the diagnosis and treatment of pediatric stroke / L. C. Jordan, A. E. Hillis // Nat Rev Neurol. – 2011. – Vol. 7, №4.– Р. 199–208.Jordan L. C. Challenges in the diagnosis and treatment of pediatric stroke / L. C. Jordan, A. E. Hillis // Nat Rev Neurol. – 2011. – Vol. 7, №4.– Р. 199–208.Khan S. Hereditary thrombophilia / S. Khan, J.D. Dickerman // Thromb J.– 2006.– №4 .– Р.15.Khan S. Hereditary thrombophilia / S. Khan, J.D. Dickerman // Thromb J.– 2006.– №4 .– Р.15.Lack of progressive arteriopathy and stroke recurrence among children with cryptogenic stroke / S. Darteyre, S. Chabrier, E. Presles [et al.] // Neurology. – 2012.– Vol. 79, №24.– Р. 2342- 2348.Lack of progressive arteriopathy and stroke recurrence among children with cryptogenic stroke / S. Darteyre, S. Chabrier, E. Presles [et al.] // Neurology. – 2012.– Vol. 79, №24.– Р. 2342- 2348.Lyle C.A. Childhood arterial ischemic stroke: a review of etiologies, antithrombotic treatments, prognostic factors, and priorities for future research / C.A. Lyle, T.J. Bernard, N.A. Goldenberg // Semin Thromb Hemost.– 2011.– Vol. 37, №7.– Р. 786-793.Lyle C.A. Childhood arterial ischemic stroke: a review of etiologies, antithrombotic treatments, prognostic factors, and priorities for future research / C.A. Lyle, T.J. Bernard, N.A. Goldenberg // Semin Thromb Hemost.– 2011.– Vol. 37, №7.– Р. 786-793.Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young / E. S. Roach, M. R. Golomb, R. Adams [et al.] // Stroke.– 2008. – Vol. 39. – Р. 2644-2691.Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young / E. S. Roach, M. R. Golomb, R. Adams [et al.] // Stroke.– 2008. – Vol. 39. – Р. 2644-2691.Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study / C. Amlie-Lefond, T.J. Bernard, G. Sйbire [et al.] // Circulation.– 2009. – Vol. 119. – Р. 1417–1423.Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study / C. Amlie-Lefond, T.J. Bernard, G. Sйbire [et al.] // Circulation.– 2009. – Vol. 119. – Р. 1417–1423.Prothrombotic genetic risk factors in stroke: a possible different role in pediatric and adult patients / V. Djordjevic, M. Stankovic, V. Brankovic-Sreckovic [et al.] // Clin Appl Thromb Hemost.– 2012. – Vol. 18, №6. – Р. 658-661.Prothrombotic genetic risk factors in stroke: a possible different role in pediatric and adult patients / V. Djordjevic, M. Stankovic, V. Brankovic-Sreckovic [et al.] // Clin Appl Thromb Hemost.– 2012. – Vol. 18, №6. – Р. 658-661.Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging / H.J. Fullerton, Y.W. Wu, S. Sidney [et al.] // Pediatrics. – 2007. – Vol. 119, №3.– Р. 495-501.Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging / H.J. Fullerton, Y.W. Wu, S. Sidney [et al.] // Pediatrics. – 2007. – Vol. 119, №3.– Р. 495-501.The roles of anatomic factors, thrombophilia, and antithrombotic therapies in childhood-onset arterial ischemic stroke / J. B. Timothy, J. Marilyn [et al.] // Thromb Res.– 2011.– Vol. 127, №1.– Р. 6–12.The roles of anatomic factors, thrombophilia, and antithrombotic therapies in childhood-onset arterial ischemic stroke / J. B. Timothy, J. Marilyn [et al.] // Thromb Res.– 2011.– Vol. 127, №1.– Р. 6–12.The role of imaging in acute ischemic stroke / E. Tong, Q. Hou, J.B. Fiebach [et al.] // Neurosurg Focus. – 2014. – Vol. 36, №1. – Р. 3.The role of imaging in acute ischemic stroke / E. Tong, Q. Hou, J.B. Fiebach [et al.] // Neurosurg Focus. – 2014. – Vol. 36, №1. – Р. 3.Thrombophilia and first arterial ischaemic stroke: a systematic review / S. Haywood, R. Liesner., S. Pindora [et al.] // Arch Dis Child. – 2005. – Vol. 90, №4. – Р. 402-405.Thrombophilia and first arterial ischaemic stroke: a systematic review / S. Haywood, R. Liesner., S. Pindora [et al.] // Arch Dis Child. – 2005. – Vol. 90, №4. – Р. 402-405.Thrombophilic screening in young patients (<40 years) with idiopathic ischemic stroke: a controlled study / F. Dragoni, F. Chiarotti, G. Rosa-no [et al.] // Thromb Res.-Vol. 127, № 2. – Р. 85-90.Thrombophilic screening in young patients (<40 years) with idiopathic ischemic stroke: a controlled study / F. Dragoni, F. Chiarotti, G. Rosa-no [et al.] // Thromb Res.-Vol. 127, № 2. – Р. 85-90.Yang J.Y. Pediatric thrombophilia / J.Y. Yang, A.K. Chan // Pediatr Clin North Am.– 2013. – Vol. 60, №6. – Р. 1443-1462.Yang J.Y. Pediatric thrombophilia / J.Y. Yang, A.K. Chan // Pediatr Clin North Am.– 2013. – Vol. 60, №6. – Р. 1443-1462.Zadro R. Inherited prothrombotic risk factors in children with first ischemic stroke / R. Zadro, D.C. Herak // Biochem Med (Zagreb). – 2012. – Vol. 3.– Р. 298–310.Zadro R. Inherited prothrombotic risk factors in children with first ischemic stroke / R. Zadro, D.C. Herak // Biochem Med (Zagreb). – 2012. – Vol. 3.– Р. 298–310.Zadro R. Inherited prothrombotic risk factors in children with first ischemic stroke / R. Zadro, D.C. Herak // Biochem Med (Zagreb). – 2012. – Vol. 3.– Р. 298–310.

The authors declare that there are no conflicts of interest present.