(Stroke. 2000;31:1283.)
© 2000 American Heart Association, Inc.
Original Contributions |
Factor V Leiden and Antiphospholipid Antibodies Are Significant Risk Factors for Ischemic Stroke in Children
From the Institute of Thrombosis and Haemostasis (G.K., U.M., N.R., S.G., A.I.), Institute of Clinical Epidemiology (S.S., H.M.), and Pediatric Hematology Unit (G.R.), Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Correspondence to Aida Inbal, MD, Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel. E-mail aidainbal{at}hotmail.com
Background and Purpose—The association between ischemic childhood stroke and thrombophilia has been debated. We studied the prevalence of thrombophilia risk factors in 65 unrelated children with ischemic stroke compared with 145 control subjects.
Methods—Patients and control subjects were tested for antithrombin protein C and protein S deficiencies, the presence of antiphospholipid antibodies (APLA), factor V Leiden (FVL), G20210A polymorphism of factor II gene (FII G20210A), and C677T polymorphism of 5,10-methylenetetrahydrofolate reductase gene (C677T MTHFR).
Results—Of 65 children, 7 had a stroke in the neonatal/perinatal
period and therefore were analyzed separately. Thirty-one of
the remaining 58 patients with pediatric stroke (53.4%) were found to
have at least 1 thrombophilia marker compared with only 25.5% of
control subjects. None of the patients or control subjects had protein
S or antithrombin III deficiency. The prevalence of protein C
deficiency was higher among pediatric stroke patients than among
control subjects, but the difference was not statistically significant
(OR=7, 95% CI 0.75 to 65.1). Heterozygous FII G20210A and homozygous
MTHFR 677T were not associated with an increased risk for stroke
(OR=1.29, 95% CI 0.2 to 8.2; and OR=1.06, 95% CI 0.4 to 2.7,
respectively). In contrast, the presence of APLA was associated with a
>6-fold risk of stroke (OR=6.08, 95% CI 1.5 to 24.3), and the
heterozygosity for FVL increased the risk of stroke by almost 5-fold
(OR=4.82, 95% CI 1.4 to 16.5). Five patients with pediatric stroke had
a combination of 
2 thrombophilia markers, whereas none of the control
subjects had a combination of the markers. Most of the patients with
neonatal/perinatal stroke were found to have at least 1 thrombophilia
marker.
Conclusions—These data suggest that the prevalence of thrombophilia markers is increased in children with stroke compared with control subjects and, specifically, that FVL and APLA contribute significantly to stroke occurrence.
Key Words: child • stroke, ischemic • thrombophilia
This article has been cited by other articles:
 |
|
 |
|
  E. Aoun, K. Musallam, I Uthman, A Beydoun, T El-Hajj, and A. Taher Childhood stroke in a child with familial Mediterranean fever carrying several prothrombotic risk factors Lupus, August 1, 2009; 18(9): 845 - 847. [Abstract] [PDF]
|
|
|
|
 |
|
 D. C. Herak, M. R. Antolic, J. L. Krleza, M. Pavic, S. Dodig, V. Duranovic, A. B. Brkic, and R. Zadro Inherited Prothrombotic Risk Factors in Children With Stroke, Transient Ischemic Attack, or Migraine Pediatrics, April 1, 2009; 123(4): e653 - e660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Golomb, H. J. Fullerton, U. Nowak-Gottl, G. deVeber, and for the International Pediatric Stroke Study Group Male Predominance in Childhood Ischemic Stroke: Findings From the International Pediatric Stroke Study Stroke, January 1, 2009; 40(1): 52 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Simchen, G. Goldstein, A. Lubetsky, T. Strauss, E. Schiff, and G. Kenet Factor V Leiden and Antiphospholipid Antibodies in Either Mothers or Infants Increase the Risk for Perinatal Arterial Ischemic Stroke Stroke, January 1, 2009; 40(1): 65 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. O. Dundar, O. Duman, A. Aralasmak, and S. Haspolat Ischemic Cerebral Infarction in an Infant Following Gonadotropin Treatment for Undescended Testes J Child Neurol, November 1, 2008; 23(11): 1324 - 1327. [Abstract] [PDF]
|
|
|
|
|
|
J. W. Heil, L. Malinowski, A. Rinderknecht, J. P. Broderick, and D. Franz Use of Intravenous Tissue Plasminogen Activator in a 16-Year-Old Patient with Basilar Occlusion J Child Neurol, September 1, 2008; 23(9): 1049 - 1053. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Descloux, I. Durieu, P. Cochat, D. Vital Durand, J. Ninet, N. Fabien, and R. Cimaz Paediatric systemic lupus erythematosus: prognostic impact of antiphospholipid antibodies Rheumatology, February 1, 2008; 47(2): 183 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gokben, A. Tosun, N. Bayram, G. Serdaroglu, M. Polat, K. Kavakli, and H. Tekgul Arterial Ischemic Stroke in Childhood: Risk Factors and Outcome in Old Versus New Era J Child Neurol, October 1, 2007; 22(10): 1204 - 1208. [Abstract] [PDF]
|
|
|
|
|
|
T. N.K. Raju, K. B. Nelson, D. Ferriero, J. K. Lynch, and and the NICHD-NINDS Perinatal Stroke Workshop Part Ischemic Perinatal Stroke: Summary of a Workshop Sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke Pediatrics, September 1, 2007; 120(3): 609 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Duran, B. Biner, and M. Demir Factor VIII Levels in Children With Ischemic Stroke Clinical and Applied Thrombosis/Hemostasis, July 1, 2007; 13(3): 334 - 335. [PDF]
|
|
|
|
 |
|
 S. Austin, H. Cohen, and N. Losseff Haematology and neurology J. Neurol. Neurosurg. Psychiatry, April 1, 2007; 78(4): 334 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ozyurek, G. Balta, A. Degerliyurt, H. Parlak, S. Aysun, and A. Gurgey Significance of Factor V, Prothrombin, MTHFR, and PAI-1 Genotypes in Childhood Cerebral Thrombosis Clinical and Applied Thrombosis/Hemostasis, April 1, 2007; 13(2): 154 - 160. [Abstract] [PDF]
|
|
|
|
|
|
O. Hudaoglu, S. Kurul, U. Yis, E. Dirik, H. Cakmakci, and S. Men Basilar Artery Thrombosis in a Child Heterozygous for Prothrombin Gene G20210A Mutation J Child Neurol, March 1, 2007; 22(3): 329 - 331. [Abstract] [PDF]
|
|
|
|
|
|
N. Bednarek, P. Morville, G. Delebarre, A. Akhavi, and C. Sommer Necrotic Skin Lesions and Cerebral Infarction in the Newborn: Two Case Reports J Child Neurol, March 1, 2007; 22(3): 354 - 357. [Abstract] [PDF]
|
|
|
|
|
|
N. Akar, B. Donmez, and G. Deda FXIII Gene Val34Leu Polymorphism in Turkish Children with Cerebral Infarct J Child Neurol, February 1, 2007; 22(2): 222 - 224. [Abstract] [PDF]
|
|
|
|
|
|
B. Voetsch, R. C. Jin, C. Bierl, K. S. Benke, G. Kenet, P. Simioni, F. Ottaviano, B. P. Damasceno, J. M. Annichino-Bizacchi, D. E. Handy, et al. Promoter Polymorphisms in the Plasma Glutathione Peroxidase (GPx-3) Gene: A Novel Risk Factor for Arterial Ischemic Stroke Among Young Adults and Children Stroke, January 1, 2007; 38(1): 41 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Vagiakou, K. A. Voudris, Y. Dimitriou, A. Skardoutsou, and S. Mastroyianni Different Additional Risk Factors for Cerebral Infarctions Associated With the Factor V Leiden Mutation in a Family J Child Neurol, October 1, 2006; 21(10): 903 - 907. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Schneppenheim and J. Greiner Thrombosis in Infants and Children Hematology, January 1, 2006; 2006(1): 86 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Lynch, C. J. Han, L. E. Nee, and K. B. Nelson Prothrombotic Factors in Children With Stroke or Porencephaly Pediatrics, August 1, 2005; 116(2): 447 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Golomb, J. Biller, J. L. Smith, M. Edwards-Brown, J. C. Sanchez, T. D. Nebesio, and B. P. Garg A 10-Year-Old Girl With Coexistent Moyamoya Disease and Graves' Disease J Child Neurol, July 1, 2005; 20(7): 620 - 624. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Jabbour, A. Taher, A. Shamseddine, and S. F. Atweh Moyamoya Syndrome With Intraventricular Hemorrhage in an Adult With Factor V Leiden Mutation Arch Neurol, July 1, 2005; 62(7): 1144 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tzoufi, S. Giotopoulou, P. Papadimitriou, E. Dokou, N. I. Kolaitis, A. Siamopoulou, and G. Vartholomatos Genetic Risk Factors Associated With Thrombosis in Children With Congenital Neurologic Disorders J Child Neurol, June 1, 2005; 20(6): 509 - 512. [Abstract] [PDF]
|
|
|
|
|
|
M. Tzoufi, S. Giotopoulou, P. Papadimitriou, E. Dokou, N. I. Kolaitis, A. Siamopoulou, and G. Vartholomatos Genetic Risk Factors Associated With Thrombosis in Children With Congenital Neurologic Disorders J Child Neurol, June 1, 2005; 20(6): 509 - 512. [Abstract] [PDF]
|
|
|
|
 |
|
 S Haywood, R Liesner, S Pindora, and V Ganesan Thrombophilia and first arterial ischaemic stroke: a systematic review Arch. Dis. Child., April 1, 2005; 90(4): 402 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Bowen, C. R. Burak, and T. F. Barron Childhood Ischemic Stroke in a Nonurban Population J Child Neurol, March 1, 2005; 20(3): 194 - 197. [Abstract] [PDF]
|
|
|
|
|
|
R. Duran, B. Biner, M. Demir, C. Celtik, and S. Karasalihoglu Factor V Leiden Mutation and Other Thrombophilia Markers in Childhood Ischemic Stroke Clinical and Applied Thrombosis/Hemostasis, January 1, 2005; 11(1): 83 - 88. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Ashwal, B. S. Russman, P. A. Blasco, G. Miller, A. Sandler, M. Shevell, and R. Stevenson Practice Parameter: Diagnostic assessment of the child with cerebral palsy: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society Neurology, March 23, 2004; 62(6): 851 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Fullerton and E. von Scheven Back to school on APS: Rethinking the risk of recurrent stroke in children Neurology, January 27, 2004; 62(2): 172 - 173. [Full Text] [PDF]
|
|
|
|
|
|
S. Lanthier, F. J. Kirkham, L. G. Mitchell, R. M. Laxer, E. Atenafu, C. Male, M. Prengler, T. Domi, A. K.C. Chan, R. Liesner, et al. Increased anticardiolipin antibody IgG titers do not predict recurrent stroke or TIA in children Neurology, January 27, 2004; 62(2): 194 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kurnik, A. Kosch, R. Strater, R. Schobess, C. Heller, and U. Nowak-Gottl Recurrent Thromboembolism in Infants and Children Suffering From Symptomatic Neonatal Arterial Stroke: A Prospective Follow-Up Study Stroke, December 1, 2003; 34(12): 2887 - 2892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Katsarou, A. Attilakos, S. Fessatou, H. Tsapra, V. Tzavara, and C. Dracou Anti-{beta}2-Glycoprotein I Antibodies and Ischemic Stroke in a 20-Month-Old Boy Pediatrics, July 1, 2003; 112(1): 188 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Besnier, C Frances, A Ankri, M Aiach, and J C Piette Factor V Leiden mutation in Sneddon syndrome Lupus, May 1, 2003; 12(5): 406 - 408. [Abstract] [PDF]
|
|
|
|
|
|
P. A. Nigrovic, R. C. Fuhlbrigge, and R. P. Sundel Raynaud's Phenomenon in Children: A Retrospective Review of 123 Patients Pediatrics, April 1, 2003; 111(4): 715 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sanna, M. L. Bertolaccini, M. J. Cuadrado, M. A. Khamashta, and G. R. V. Hughes Central nervous system involvement in the antiphospholipid (Hughes) syndrome Rheumatology, February 1, 2003; 42(2): 200 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Simsic, W. E. Uber, J. Lazarchick, and S. M. Bradley Systemic-to-pulmonary artery shunt thrombosis in a neonate with factor V Leiden mutation Ann. Thorac. Surg., December 1, 2002; 74(6): 2179 - 2181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tormene, P. Simioni, P. Prandoni, F. Franz, P. Zerbinati, G. Tognin, and A. Girolami The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study Blood, September 18, 2002; 100(7): 2403 - 2405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Deda, D. Icagasioglu, H. Qaksen, and N. Akar Combined Genetic Defects in a Child With Ischemic Stroke: Case Report J Child Neurol, July 1, 2002; 17(7): 533 - 534. [Abstract] [PDF]
|
|
|
|
|
|
K. Juul, A. Tybjarg-Hansen, R. Steffensen, S. Kofoed, G. Jensen, and B. G. Nordestgaard Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses Blood, June 17, 2002; 100(1): 3 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Avcin, R Cimaz, and P L Meroni Recent advances in antiphospholipid antibodies and antiphospholipid syndromes in pediatric populations Lupus, January 1, 2002; 11(1): 4 - 10. [Abstract] [PDF]
|
|
|
|
|
|
J.Y. Streifler, N. Rosenberg, A. Chetrit, R. Eskaraev, B.A. Sela, R. Dardik, A. Zivelin, B. Ravid, J. Davidson, U. Seligsohn, et al. Cerebrovascular Events in Patients With Significant Stenosis of the Carotid Artery Are Associated With Hyperhomocysteinemia and Platelet Antigen-1 (Leu33Pro) Polymorphism Stroke, December 1, 2001; 32(12): 2753 - 2758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Strater, K. Kurnik, C. Heller, R. Schobess, P. Luigs, and U. Nowak-Gottl Aspirin Versus Low-Dose Low-Molecular-Weight Heparin: Antithrombotic Therapy in Pediatric Ischemic Stroke Patients: A Prospective Follow-Up Study Stroke, November 1, 2001; 32(11): 2554 - 2558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Lynch, K. B. Nelson, C. J. Curry, and J. K. Grether Cerebrovascular Disorders in Children With the Factor V Leiden Mutation J Child Neurol, October 1, 2001; 16(10): 735 - 744. [Abstract] [PDF]
|
|