Antithrombin deficiency: A pediatric disorder

Natalie Smith, Beth Boulden Warren, Julie Smith, Linda Jacobson, Jennifer Armstrong, Jihye Kim, Jorge Di Paola, Marilyn Manco-Johnson

Research output: Contribution to journalArticlepeer-review


Introduction: Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilic disorder. Guidelines do not support routine testing of children based on personal or familial thrombosis. Aim: To investigate clinical, genetic and laboratory profiles of AT deficient children and their affected family members. Materials and methods: Data were analyzed from a prospective cohort of pediatric patients with AT deficiency. The SERPINC1 gene was sequenced for all individuals with available DNA. AT, thromboelastography (TEG), calibrated automated thrombogram (CAT), D-dimer, thrombin-antithrombin complex (TAT) and factor VIII activity were performed on patient samples. Results: Thirty-six individuals from 11 families had AT deficiency (activities 45–70 U/dL) with incident thrombosis in 13 children and 10 adults (64% overall). Three neonates presented with middle cerebral artery and/or aortic occlusions with inferior vena cava and cerebral or renal vein thromboses in 2 of the 3. Two pre-pubertal children were symptomatic, one with cerebral venous sinus thrombosis who suffered recurrent arterial and venous thrombi. Both Type I and Type II AT deficiencies conferred a high severity of thromboses. Heterozygous SERPINC1 mutations were identified in seven families; three were novel, resulting in missense, splice site and frameshift alterations. Thrombin generation (CAT) was increased in all asymptomatic affected patients including 9 children and 1 adult. Conclusions: Genetic AT deficiency often presents in infants and children, warranting laboratory evaluation based on personal and family history. Increased thrombin generation was detected in all asymptomatic children and adults, suggesting a possible role in detecting and monitoring individuals at risk for thrombosis.

Original languageEnglish
Pages (from-to)45-51
Number of pages7
JournalThrombosis Research
StatePublished - Jun 2021


  • Antithrombin deficiency
  • Antithrombin mutations
  • Calibrated automated thrombogram
  • Global assays
  • Thromboelastography
  • Thrombosis


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