Protein C deficiency as the major cause of thrombophilias in childhood.

Abstract

Genetic predisposition of thromboembolism depends on the racial background. Factor V Leiden (G1691A) and factor II mutation (G20210A) are the leading causes of inherited thrombophilias in Caucasians, but are not found in Asian ancestries. Protein S (PS), protein C (PC) and antithrombin (AT) activity are reportedly low in 65% of adult Japanese 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 (SERPINC1: 5%). Recently, several studies have revealed an outline of inherited thrombophilias in Japanese 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 (1362delG), 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.

• Authors: Shouichi Ohga, Akira Ishiguro, Yukihiro Takahashi, Midori Shima, Masashi Taki, Masatoki Kaneko, Kotaro Fukushima, Dongchon Kang, Toshiro Hara, Japan Childhood Thrombophilia Study Group
• Journal: Pediatrics international : official journal of the Japan Pediatric Society (Pediatr Int) Vol. 55 Issue 3 Pg. 267-71 (Jun 2013) ISSN: 1442-200X [Electronic] Australia
• PMID: 23521084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

Chemical References

• Anticoagulants
• Antithrombins
• Protein C
• Protein S

Topics

• Adolescent
• Anticoagulants (therapeutic use)
• Antithrombins (blood)
• Blood Coagulation Tests
• Child
• Child, Preschool
• Diagnosis, Differential
• Early Diagnosis
• Early Medical Intervention
• Humans
• Infant
• Infant, Newborn
• Japan
• Protein C (metabolism)
• Protein C Deficiency (blood, diagnosis, drug therapy)
• Protein S (metabolism)
• Protein S Deficiency (blood, diagnosis, drug therapy, genetics)
• Reference Values
• Thrombophilia (blood, diagnosis, genetics)