Mutations and Polymorphisms in Genes Affecting Haemostasis Components in Children with Thromboembolic Events

Abstract

The distribution of mutations/polymorphisms in genes affecting haemostasis [factor V Leiden (FVL), FV H1298R (FVR₂), FII 20210A, b-Fib 455G→A, FXIII V34L, PAI-1 4G, HPA-1b] among 141 children with thrombosis at various sites and 103 controls was compared. Additionally, the carriage of these mutations/polymorphisms was associated with the levels of their corresponding proteins in thrombosed children. Thrombosis was more frequent in boys (p = 0.021). No studied mutation/polymorphism was found to be a risk factor for thrombosis, except for FVL (odds ratio 3.8, 95% CI 1.4–10.6). The risk of thrombosis for FVL carriers was twice as high in children with an idiopathic thrombosis (odds ratio 5.4) than in thrombosed children with an underlying disease or a triggering event (odds ratio 2.7). FVL carriers had an odds ratio of 5.9 (95% CI 1.8–19.6) when FVR₂ was absent. In thrombosed children, the activated protein C resistance ratio was significantly lower in the presence of FVL (p < 0.001). Prothrombin and fibrinogen levels, although higher in FII 20210A and b-Fib 455G→A carriers, did not reach statistical significance.

Fibrinolytic parameters in children with noncatheter thrombosis: a pilot study

“…The role of elevated PAI concentrations and PAI-4G/ 4G genotype in thrombosis is currently being investigated [15]. Though an elevation in PAI-1 concentration is thought to incur a moderate thrombotic risk, the presence of the 4G/4G genotype is not clearly associated with thrombosis in children [16][17][18]. In our patients, we did not screen for the presence of 4G/4 G genotype but elected to test the PAI-1 activity as the PAI-1 concentrations are affected by other environmental factors.…”

Gene Variations in the Protein C and Fibrinolytic Pathway: Relevance for Severity and Outcome in Pediatric Sepsis

“…Although higher FXIII activity was found for 34Leu carriers, 140 the Val34Leu polymorphism was not associated with susceptibility to venous thrombosis or ischemic stroke. 100,103,140,141 In two large studies, Leu/Leu genotype 142 and 34Leu allele 19 revealed a protective effect on venous thrombosis.…”

“…8 In adult patients with severe pneumonia, the 4G allele has also been associated with increased susceptibility to community-acquired pneumonia, increased mortality, and fewer ventilator-free days. 98,99 The SERPINE1 4G/5G polymorphism has already been extensively studied in venous thrombosis 18,90,100,101 and ischemic stroke. [102][103][104][105][106] Most studies, including both small and large groups of patients, failed to associate this polymorphism with disease.…”

“…118 In children, this polymorphism was not associated with susceptibility to ischemic stroke 103,119 or venous thrombosis. 90,100,120 It has been suggested that high values of plasma fibrinogen may be associated with thromboembolic disorders mainly in elderly, and that elevated fibrinogen values reflect accumulated age-associated risk factors for cardiovascular disease. 121 The FGA A312G (Thr312Ala) polymorphism (rs6050) is associated with fibrin fibers thickness and α-chain crosslinking, hence difference in resistance to fibrinolysis.…”