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Antithrombin deficiency: A pediatric disorder.

Natalie Smith1, Beth Boulden Warren1, Julie Smith1

  • 1Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

Thrombosis Research
|March 16, 2021
PubMed
Summary
This summary is machine-generated.

Hereditary antithrombin deficiency in children can cause severe thrombosis. Increased thrombin generation in asymptomatic individuals suggests a potential method for early detection and monitoring of thrombosis risk.

Keywords:
Antithrombin deficiencyAntithrombin mutationsCalibrated automated thrombogramGlobal assaysThromboelastographyThrombosis

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Area of Science:

  • Pediatric Hematology
  • Thrombophilia Genetics
  • Molecular Diagnostics

Background:

  • Hereditary antithrombin (AT) deficiency is an autosomal dominant disorder linked to thrombosis.
  • Current guidelines do not recommend routine genetic testing for AT deficiency in children based solely on personal or family history of thrombosis.

Purpose of the Study:

  • To characterize the clinical, genetic, and laboratory profiles of children with AT deficiency and their affected family members.
  • To investigate the utility of thrombin generation assays in identifying thrombosis risk in asymptomatic individuals.

Main Methods:

  • Prospective cohort study of pediatric patients with AT deficiency.
  • Genetic sequencing of the SERPINC1 gene.
  • Laboratory assays including antithrombin activity, thromboelastography (TEG), calibrated automated thrombogram (CAT), D-dimer, thrombin-antithrombin complex (TAT), and factor VIII activity.

Main Results:

  • Thirty-six individuals from 11 families were identified with AT deficiency (45-70 U/dL).
  • Thrombosis occurred in 64% of individuals (13 children, 10 adults), including severe neonatal cases and symptomatic pre-pubertal children.
  • Heterozygous SERPINC1 mutations were found in seven families, with three novel mutations identified. Increased thrombin generation (CAT) was observed in all asymptomatic affected individuals.

Conclusions:

  • Genetic antithrombin deficiency frequently manifests in infants and children, necessitating laboratory evaluation guided by clinical and family history.
  • Elevated thrombin generation in asymptomatic patients suggests its potential as a biomarker for thrombosis risk assessment and monitoring.