Naslov
Is inherited thrombophilia testing justified in children with perinatal arterial ishemic stroke?

Autori
Herak Coen, Desiree ; Radic Antolic, Margareta ; Horvat, Ivana ; Leniček Krleža, Jasna ; Đuranović, Vlasta ; Zadro, Renata

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
CiTH / - , 2014, 42-42

Skup
Congress on Controversies in Thrombosis & Hemostasis Berlin

Mjesto i datum
Berlin, Njemačka, 30.10.2014. - 01.11.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
perinatal arterial ishemic stroke, polymorphisms, inherited thrombophilia

Sažetak
Statement: Perinatal arterial ischemic stroke (PAIS) has received increased attention as an important cause of cerebral palsy and other neurological and cognitive disabilities. The incidence of PAIS is the highest among pediatric stroke patients, being as high as the incidence of large vessel ischemic stroke in adults. However, the pathogenesis of PAIS is still poorly understood and seems to be multifactorial including obstetrical and maternal factors, perinatal conditions, infections, thrombophilia and many others. Despite the fact that PAIS is as much as 17 times more common than arterial ischemic stroke at any time in childhood and adolescence, much less is known about the impact of inherited thrombophilia on the occurrence of PAIS. As compared to numerous published population studies and meta-analysis that have investigated inherited thrombophilia as a risk factor for childhood arterial ischemic stroke, available information in children with PAIS are limited to several case reports and few case- control studies only. Method: In order to elucidate the possible role of inherited thrombophilia in the etiology of PAIS we have performed a case-control study in 35 Croatian children (20 boys and 15 girls) with a confirmed diagnosis of PAIS and 100 age- and sex-matched control subjects from the same geographic region. A genotype analysis of 14 polymorphisms in 12 candidate genes encoding proteins of the coagulation and fibrinolysis systems (FV Leiden, FV HR2, FII G20210A, β- fibrinogen -455G>A, FXIII-A Val34Leu, PAI-1 4G/5G), homocysteine metabolism (MTHFR C677T, MTHFR A1298C) intermediate risk factors (ACE I/D, apoE ε2-4) was performed by using a multilocus genotyping assay (CVD Strip Assay, ViennaLab, Austria) and for human platelet alloantigens (HPA-1, -2, -3 and - 5) by ASO-PCR with sequence-specific primers according to Klüter et al. (Vox Sang 1996 ; 71: 121-5). Results: Among investigated polymorphisms, we have found a strong association between the presence of FV Leiden and PAIS (OR=8.29 ; 95% CI=1.95-35.24, P=0, 004). Furthermore a 2.89- fold increased risk for PAIS was found in carriers of the ACE I/D genotype (95% CI=1.05- 7.93 ; P=0.038), whereas the presence of at least one HPA-3b allele was associated with more than a 2-fold lower risk for the development of PAIS (OR=0.39 ; 95% CI=0.18-0.86, P=0.020). The presence of combined heterozygosity for FV Leiden and FV HR2 (2 out of 7 heterozygotes for FV Leiden) was identified in children with PAIS only. Moreover a 5.51-fold increased risk for PAIS (95% CI=1.22-24.82) was observed in children with the genotype combination GA (FV Leiden) and AA (wild type FV HR2). Conclusion: As this study has clearly demonstrated the role of inherited thrombophilia in the pathogenesis of PAIS we strongly support inherited thrombophilia testing. However, by performing the first-line thrombophilia screening, including FV Leiden, FII G20210A and MTHFR C677T, we would be able only to identify the strongest association between FV Leiden and PAIS as FII G20210A and MTHFR C677T were not found to be associated with PAIS in Croatian children. The extended inherited thrombophiliatesting panel has enabled us to identify new polymorphisms associated with PAIS and combined genetic traits that have to be confirmed in other population studies.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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