Age-specific onset and distribution of the natural anticoagulant deficiency in pediatric thromboembolism

Pediatr Res. 2016 Jan;79(1-1):81-6. doi: 10.1038/pr.2015.180. Epub 2015 Sep 15.

Abstract

Background: The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation.

Methods: We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged ≤20 y using the screening of plasma activity and genetic analysis.

Results: Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism.

Conclusion: Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated Protein C Resistance / blood
  • Activated Protein C Resistance / diagnosis
  • Activated Protein C Resistance / epidemiology*
  • Activated Protein C Resistance / genetics
  • Adolescent
  • Age of Onset
  • Antithrombin III / analysis
  • Antithrombin III / genetics
  • Antithrombin III Deficiency / blood
  • Antithrombin III Deficiency / diagnosis
  • Antithrombin III Deficiency / epidemiology*
  • Antithrombin III Deficiency / genetics
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / etiology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Factor V / genetics
  • Female
  • Genotype
  • Humans
  • Infant
  • Japan / epidemiology
  • Male
  • Promoter Regions, Genetic / genetics
  • Protein C / analysis
  • Protein C / genetics
  • Protein C Deficiency / blood
  • Protein C Deficiency / diagnosis
  • Protein C Deficiency / epidemiology*
  • Protein C Deficiency / genetics
  • Protein S / analysis
  • Protein S / genetics
  • Protein S Deficiency / blood
  • Protein S Deficiency / diagnosis
  • Protein S Deficiency / epidemiology*
  • Protein S Deficiency / genetics
  • Prothrombin / genetics
  • Thromboembolism / epidemiology
  • Thromboembolism / etiology*
  • Thrombophilia / blood
  • Thrombophilia / diagnosis
  • Thrombophilia / epidemiology
  • Thrombophilia / genetics*

Substances

  • Protein C
  • Protein S
  • factor V Leiden
  • Antithrombin III
  • Factor V
  • Prothrombin