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Protein C deficiency as the major cause of thrombophilias in childhood
Author(s) -
Ohga Shouichi,
Ishiguro Akira,
Takahashi Yukihiro,
Shima Midori,
Taki Masashi,
Kaneko Masatoki,
Fukushima Kotaro,
Kang Dongchon,
Hara Toshiro
Publication year - 2013
Publication title -
pediatrics international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.49
H-Index - 63
eISSN - 1442-200X
pISSN - 1328-8067
DOI - 10.1111/ped.12102
Subject(s) - medicine , compound heterozygosity , protein c deficiency , protein s deficiency , protein c , thrombophilia , purpura fulminans , mutation , asymptomatic , factor v , protein s , antithrombin , pediatrics , gene mutation , thrombosis , gastroenterology , venous thrombosis , genetics , surgery , gene , biology , heparin
Genetic predisposition of thromboembolism depends on the racial background. Factor V L eiden ( G 1691 A ) and factor II mutation ( G 20210 A ) are the leading causes of inherited thrombophilias in C aucasians, but are not found in A sian ancestries. Protein S ( PS ), protein C ( PC ) and antithrombin ( AT ) activity are reportedly low in 65% of adult J apanese patients with deep vein thrombosis. Approximately half of the patients with each deficiency carry the heterozygous mutation of PS ( PROS1 ; 20%), PC ( PROC ; 10%), and AT genes ( SERPINC 1 : 5%). Recently, several studies have revealed an outline of inherited thrombophilias in J apanese children. Congenital thrombophilias in 48 patients less than age 20 years consisted of 45% PC deficiency, 15% PS deficiency and 10% AT deficiency, along with other causes. All PS ‐ and AT ‐deficient patients had a heterozygous mutation of the respective gene. On the other hand, PC ‐deficient patients were considered to carry the homozygous or compound heterozygous mutation in 50%, the heterozygous mutation in 25%, and unknown causes in the remaining 25% of patients. Half of unrelated patients with homozygous or compound heterozygous PROC mutations carried PC ‐nagoya (1362del G ), while their parents with its heterozygous mutation were asymptomatic. Most of the PC ‐deficient patients developed intracranial lesion and/or purpura fulminans within 2 weeks after birth. Non‐inherited PC deficiency also conveyed thromboembolic events in early infancy. The molecular epidemiology of thrombosis in Asian children would provide a clue to establish the early intervention and optimal anticoagulant therapy in pediatric PC deficiency.