title: Age-specific onset and distribution of the natural anticoagulant deficiency in pediatric thromboembolism.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Ichiyama
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.affiliation: Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ochiai
authors.affiliation: Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Matsunaga
authors.affiliation: Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kusuda
authors.affiliation: Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ishimura
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Takimoto
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Hotta
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.affiliation: Comprehensive Maternity and Perinatal Care Center, Kyushu University Hospital, Fukuoka, Japan.|Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D000293:Adolescent; D017668:Age of Onset; D000990:Antithrombin III / Q000032:analysis / Q000235:genetics; D020152:Antithrombin III Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005165:Factor V / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D011486:Protein C / Q000032:analysis / Q000235:genetics; D020151:Protein C Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D017293:Protein S / Q000032:analysis / Q000235:genetics; D018455:Protein S Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology*; D019851:Thrombophilia / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D011486:Protein C; D017293:Protein S; C095381:factor V Leiden; D000990:Antithrombin III; D005165:Factor V; D011516:Prothrombin