Protein C deficiency as the major cause of thrombophilias in childhood

Area of Science:

• Hematology
• Genetics
• Pediatrics

Background:

• Thromboembolism predisposition varies by race.
• Factor V Leiden and factor II mutations are common in Caucasians but absent in Asians.
• Low protein S (PS), protein C (PC), and antithrombin (AT) activity are observed in Japanese adults with deep vein thrombosis.

Purpose of the Study:

• To outline inherited thrombophilias in Japanese children.
• To investigate the genetic basis of congenital thrombophilias in pediatric patients.
• To inform early intervention and treatment strategies for pediatric protein C deficiency.

Main Methods:

• Analysis of congenital thrombophilias in 48 Japanese patients under 20 years old.
• Identification of mutations in protein S (PROS1), protein C (PROC), and antithrombin (SERPINC1) genes.
• Comparison of genetic findings between pediatric and adult thrombophilia patients.

Main Results:

• Protein C deficiency was the most frequent congenital thrombophilia (45%) in Japanese children, followed by PS deficiency (15%) and AT deficiency (10%).
• Homozygous or compound heterozygous mutations in PROC were found in 50% of PC-deficient children, with PC-nagoya (1362delG) identified in half of these cases.
• Severe neonatal complications like intracranial lesions and purpura fulminans were common in PC-deficient infants, even with non-inherited deficiency.

Conclusions:

• Inherited thrombophilias in Japanese children have a distinct molecular epidemiology compared to Caucasians.
• Protein C deficiency, particularly with homozygous/compound heterozygous mutations, poses significant risks in early infancy.
• Understanding the molecular basis of pediatric thrombophilia is essential for developing targeted interventions and optimizing anticoagulant therapy.