Impact of high risk thrombophilia status on recurrence among children and adults with VTE: An observational multicenter cohort study

Brüwer, Gloria; Limperger, Verena; Kenet, Gili; Klostermeier, Ulrich C.; Shneyder, Maria; Degenhardt, Frauke; Finckh, Ulrich; Heller, Christine; Holzhauer, Susanne; Trappe, Ralf Ulrich; Kentouche, Karim; Knoefler, Ralf; Kurnik, Karin; Krümpel, Anne; Lauten, Melchior; Manner, Daniela; Mesters, Rolf M.; Junker, Ralf; Nowak‐Göttl, Ulrike

doi:10.1016/j.bcmd.2016.10.024

Cited by 11 publications

(10 citation statements)

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“…Specifically, as demonstrated recently in children with recurrent deep venous thrombosis and thromboembolic stroke, heterozygous antithrombin deficiency is a major risk factor for second AIS events. 31 In addition, data presented here confirm an increased risk for recurrent stroke events in the subgroup of patients with an underlying vasculopathy. 15,22,32–35…”

Section: Discussionsupporting

confidence: 71%

Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population

et al. 2019

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Risk factors for arterial ischemic stroke in children include vasculopathy and prothrombotic risk factors but their relative importance to recurrent stroke is uncertain. Data on recurrent stroke from databases held in Canada (Toronto), Germany (Kiel-Lübeck/Münster), and the UK (London/Southampton) were pooled. Data were available from 894 patients aged 1 month to 18 years at first stroke (median age, 6 years) with a median follow-up of 35 months. Among these 894 patients, 160 (17.9%) had a recurrence between 1 day and 136 months after the first stroke (median, 3.1 months). Among 288 children with vasculopathy, recurrence was significantly more common [hazard ratio (HR) 2.5, 95% confidence interval (95% CI) 1.92-3.5] compared to the rate in children without vasculopathy. Adjusting for vasculopathy, isolated antithrombin deficiency (HR 3.9; 95% CI: 1.4-10.9), isolated elevated lipoprotein (a) (HR 2.3; 95% CI: 1.3-4.1), and the presence of more than one prothrombotic risk factor (HR 1.9; 95% CI: 1.12-3.2) were independently associated with an increased risk of recurrence. Recurrence rates calculated per 100 person-years were 10 (95% CI: 3-24) for antithrombin deficiency, 6 (95% CI: 4-9) for elevated lipoprotein (a), and 13 (95% CI: 7-20) for the presence of more than one prothrombotic risk factor. Identifying children at increased risk of a second stroke is important in order to intensify measures aimed at preventing such recurrences.

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Section: Discussionsupporting

confidence: 71%

Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population

et al. 2019

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Section: Discussionsupporting

confidence: 71%

Recurrent Stroke: The Role of Thrombophilia in a Large International Pediatric Stroke Population

deVeber

Kirkham²,

Shannon

et al. 2018

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Risk factors for arterial ischaemic stroke in children include vasculopathy and prothrombotic risk factors but their relative importance to recurrent stroke is uncertain. Data on recurrent stroke from the databases held in Canada (Toronto), Germany (Kiel-Lübeck/Münster), and UK (London/Southampton) were pooled. Data were available from 894 patients aged 1 month to 18 years at first stroke (median age 6 years) with a median follow-up of 35 months. 160/894 patients (17.9%) had recurrence from 1 day to 136 months after first stroke (median 3.1 months). Among 288 children with vasculopathy, recurrence was significantly more common (hazard ratio (HR) 2.5, 95% confidence intervals (CI) 1.92-3.5) compared to children without vasculopathy. Adjusting for vasculopathy, isolated antithrombin deficiency (HR 3.9; 95%CI 1.4-10.9), isolated elevated lipoprotein (a) (HR 2.3; 95%CI 1.3-4.1), and the presence of more than one prothrombotic risk (HR 1.9; 95%CI 1.12-3.2) were independently associated with an increased risk of recurrence. Recurrence rates calculated per 100 person-years were 10 (95%CI 3-24) for antithrombin deficiency, 6 (95%CI 4-9) for elevated lipoprotein (a), and 13 (95%CI 7-20) for the presence of more than one prothrombotic risk.Identifying children at increased for second stroke events is important in intensifying measures aimed at preventing recurrent stroke. Abstract: 199Main Text: 2630, 3 Figures, 3 Tables, 1 supplemental Figure

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“…On the other hand, the substantial risk of thrombotic events in newborn patients depends on the genetic predisposition and triggers such as asphyxia and infection. The effect size of thrombophilia genes in individuals might be augmented during the perinatal and adolescent periods according to age-associated conditions, compared to the adult patients with thromboembolism [6].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic challenge of the newborn patients with heritable protein C deficiency

et al. 2018

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AbstarctObjectiveThe diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan.Study designWe determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry.ResultPhysiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off < 10%, odds ratio = 30.0) and PC/PS-activity ratio (cut-off < 0.35, odds ratio = 22.7), with 93% sensitivity and 44% specificity for determining patients with mutation(s).ConclusionThe PC/PS-activity ratio is an effective parameter for the genetic screening of neonatal-onset PC-deficiency in Japanese population.

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Impact of high risk thrombophilia status on recurrence among children and adults with VTE: An observational multicenter cohort study

Cited by 11 publications

References 37 publications

Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population

Recurrent stroke: the role of thrombophilia in a large international pediatric stroke population

Recurrent Stroke: The Role of Thrombophilia in a Large International Pediatric Stroke Population

Diagnostic challenge of the newborn patients with heritable protein C deficiency

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