Factor V Leiden and Prothrombin Gene G 20210 A Variant in Children with Ischemic Stroke

Summary

Objective: To investigate if the factor V Leiden mutation (F-V-LM) and/or the prothrombin gene G 20210 A variant (P-G20210A-V) are risk factors for acute stroke in Austrian children. Patients: 33 children with acute ischemic stroke documented by computer tomography and/or magnetic resonance imaging of the brain were enrolled in an open multicenter survey. Results: 6/33 children had F-V-LM (5 heterozygous, 1 homozygous). This represents 18% (95% CI: 6.7-39.9%) of our pediatric stroke population and thus exceeds the expected prevalence in the Austrian population of 4,6% (Fischer’s exact test, p = 0.01). F-V-LM was not found in 11 children with neonatal stroke but in 6/22 children with stroke after the neonatal period. 5/6 children with F-V-LM had an underlying disorder that is a risk factor for stroke in children. The P-G20210A-V was detected in 1/26 (3.85%; 95% CI: 0.1-21.4%) patients. Comparison of the prevalence of P-G20210A-V in our study with that in the general population of Austria of 1% revealed no statistical significance (Fischer’s exact test, p = 0.38). Conclusion: Our data suggest that the F-V-LM is a risk factor for acute stroke in Austrian children beyond the neonatal period. The P-G20210A-V apparently does not represent a risk factor for stroke in Austrian children.

• References

• 1 Broderick J, Talbot T, Prenger E, Leach A, Brott T. Stroke in children within a major metropolitan area: the surprising importance of intracerebral hemorrhage. J Child Neurol 1993; 8: 250-5.
• 2 Riela AR, Roach ES. Etiology of stroke in children. J Child Neurol 1993; 8: 201-20.
• 3 Butler IJ. Cerebrovascular disorders of childhood. J Child Neurol 1993; 8: 197-200.
• 4 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a pre viously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
• 5 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
• 6 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346: 1133-4.
• 7 Zenz W, Muntean W, Gallistl S, Leschnik B, Beitzke A. Inherited resistance to activated protein C in a boy with multiple thromboses in early infancy. Eur J Pediat 1995; 154: 285-8.
• 8 Aschka I, Aumann V, Bergmann F, Budde U, Eberl W, Eckhof-Donovan S, Krey S, Nowak-Göttl U, Schobess R, Sutor AH, Wendisch J. Schneppen heim R.. Prevalence of factor V leiden in children with thrombo-embolism. Eur J Pediatr 1996; 155: 1009-14.
• 9 Nowak-Göttl U, Koch HG, Aschka I, Kohlhase B, Vielhaber H, Kurlemann G, Oleszuk-Raschke HG, Jürgens H, Schneppenheim R. Resistance to activated protein C (APCR) in children with venous or arterial thromboembolism. Br J Haematol 1996; 92: 992-8.
• 10 Ridker PM, Hennekens CH, Lindpaintner K, Stamfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke and venous thrombosis in apparently healthy men. N Eng J Med 1995; 332: 912-7.
• 11 Rosendaal FR, Siscovick DS, Schwartz SM, Beverly RK, Psaty BM, Long-streth WT, Raghunathan TE, Koepsell TD, Reitsma PH. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 89: 2817-21.
• 12 Halbmayer WM, Haushofer A, Angerer V, Finsterer J, Fischer M. APC resistance and factor V Leiden (FV:Q⁵⁰⁶) mutation in patients with ischemic cerebral events. Blood Coagulation and Fibrinolysis 1997; 8: 361-4.
• 13 Kontula K, Ylikorkala A, Miettinen H, Vuorio A, Kauppinen-Mäkelin R, Hämäläinen L, Palomäki H, Kaste M. Arg 506 Gln factor V mutation (factor V Leiden) in patients with ischemic cerebrovascular disease and survivors of myocardial infarction. Thromb Haemost 1995; 73: 558-60.
• 14 Nowak-Göttl U, Sträter R, Dübbers A, Oleszuk-Raschke K, Vielhaber H. Ischaemic stroke in infancy and childhood:role of the Arg 506 to Gln mutation in the factor V gene. Blood Coagulation and Fibrinolysis 1996; 7: 684-8.
• 15 Ganesan V, Kelsey H, Cookson J, Osborn A, Kirkham FJ. Activated protein C resistance in childhood stroke. Lancet 1996; 347: 260.
• 16 Riikonen RS, Vahtera EM, Kekomäki RM. Physiological anticoagulants and activated protein C resistance in childhood stroke. Acta Paediatr 1996; 85: 242-4.
• 17 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and increase in venous thrombosis. Blood 1996; 88: 3698-703.
• 18 Rosendaal FR, Siscovick DS, Schwartz SM, Psaty BM, Raghunathan TE, Vos HL. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood 1997; 90: 1747-50.
• 19 Födinger M, Mannhalter C, Pabinger I, Koizar D, Rintelen C, Hörl WH, Sunder Plassmann G. Resistance to activated protein C (APC): mutation at ARG⁵⁰⁶ of coagulation factor V and vascular access thrombosis in haemodialysis patients. Nephrol Dial Transplant 1996; 11: 668-72.
• 20 Watzke HH, Schuttrumpf J, Graf S, Huber K, Panzer S. Increased prevalence of a polymorphism in the gene coding for human prothrombin in patients with coronary heart disease. Thromb Res 1997; 87: 521-6.
• 21 Bridges ND, Hellenbrand W, Latson L, Filiano J, Newburger JW, Lock JE. Transcatheter closure of patent foramen ovale after presumed paradoxical embolism. Circulation 1992; 86: 1902-8.