Factor V Leiden and Antiphospholipid Antibodies Are Significant Risk Factors for Ischemic Stroke in Children

Abstract

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 (ORϭ7, 95% CI 0.75 to 65.1). Heterozygous FII G20210A and homozygous MTHFR 677T were not associated with an increased risk for stroke (ORϭ1.29, 95% CI 0.2 to 8.2; and ORϭ1.06, 95% CI 0.4 to 2.7, respectively). In contrast, the presence of APLA was associated with a Ͼ6-fold risk of stroke (ORϭ6.08, 95% CI 1.5 to 24.3), and the heterozygosity for FVL increased the risk of stroke by almost 5-fold (ORϭ4.82, 95% CI 1.4 to 16.5). Five patients with pediatric stroke had a combination of Ն2 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.

Ischemic stroke in children: a study of the associated alterations

“…The female sex was most affected in the present study with 52% of the cases contrary to the great majority of the other studies where the male sex represents between 50 and 60% of the cases 7,11,12,[14][15][16][17] . Perhaps this is due to the association of the male sex with arterial trauma dissection as a basic cause of AIS 18 , which did not occur in this study.…”

“…Bonduel et al verified that 30% of AIS patients presented prothrombotic disorders, but this occurred in about 50% in our study 7 . This fact may be due to the great number of associated infections, principally sepsis, because the acquired deficiencies of the proteins of coagulation and thrombosis of the central nervous system, are associated with infections 6,28 , and it could also be a consequence of the inclusion of newborn in the research, because the prevalence of prothrombotic risk factors is high in this age 9,15 . The presence of more than one altered coagulation protein in one patient only probably indicates that the deficiency is acquired 6 and multiple alterations are common in cases of AIS as compared to the controls 15 and this occurred in five of our patients.…”

Perinatal stroke – risk factors and management

“…In older children with AIS, the data has been conflicting and has been hampered by the small number of cases in some of the published studies (Bonduel et al, 1999;McColl et al, 1999;Nowak-Gottl et al, 1999;Strater et al, 1999;Kenet et al, 2000). Nevertheless, there does seem to be a trend towards an increased incidence of prothrombotic abnormalities in older children with AIS Chan et al, 2000).…”

Cerebral sinovenous thrombosis in children – analysis of 5 CSVT cases from Child Neurology Clinic in Rzeszow

“…Pacjent z takimi czynnikami ryzyka zgodnie z wytycznymi CHEST 2012 [6] powinien otrzymywać leczenie przeciwzakrzepowe przez okres od 6 do 12 miesięcy po epizodzie zakrzepicy naczyń żylnych mózgowia. Mutacja Leiden czynnika V stanowi jedną z najczęstszych wrodzonych trombofilii [21]. Kliniczna ekspresja defektu Leiden charakteryzuje się znaczną różnorodnością zależną od współtowarzyszących procesów zaburzających hemostazę.…”

“…Kent i wsp. w swoich badaniach nad nawrotową zatorowością u dzieci z wrodzonymi trombofiliami podkreślają moż-liwość wystąpienia epizodów zakrzepowo-zatorowych w okresie dojrzewania i intensywnego wzrastania [21,22]. Goldenberg i wsp.…”