Genetic Aspects of Hemostasis in Children with Arterial Ischemic Stroke
Abstract
In acute and recovery periods it is obligatory to detect blood diseases and pathological conditions leading to recurrent cerebral thrombosis.
Aim of the study. To define genetic factors influencing thrombogenesis in children with AIS.
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. 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. 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.
About the Authors
A. V. Minin
St. Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Aleksey V. Minin: assistant, Psychoneurology department
St. Petersburg, Litovskaya str., 2
K. I. Pshenichnaya
St. Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Ksenia I. Pshenichnaya: M.D., professor Pediatrics department
St. Petersburg, Litovskaya str., 2
A. B. Palchik
St. Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Alexander B. Palchik: M.D., neurologist, professor Psychoneurology departmen
St. Petersburg, Litovskaya str., 2
References
1. Alekseev N.A. Haemorrhagic diathesis and thrombophilia / N.A. Alekseev. – SPb.: Gyppokrat, 2005. – Р. 516–556.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Khan S. Hereditary thrombophilia / S. Khan, J.D. Dickerman // Thromb J.– 2006.– №4 .– Р.15.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. Yang J.Y. Pediatric thrombophilia / J.Y. Yang, A.K. Chan // Pediatr Clin North Am.– 2013. – Vol. 60, №6. – Р. 1443-1462.
20. 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.
Review
For citations:
Minin A.V., Pshenichnaya K.I., Palchik A.B. Genetic Aspects of Hemostasis in Children with Arterial Ischemic Stroke. Yakut Medical Journal. 2014;(2):25-27.
Views:
2
Email this article 