[Precision diagnosis and genetic counseling for early-onset hereditary thrombosis].

Abstract

The rapid global adoption of genomic medicine has recently deepened understanding of the triggers and predisposing factors of thromboembolism. This led to a greater diagnostic significance of heritable thrombophilia, even among infants, children, adolescents, and young adults in Asian countries, whose genetic predisposition had previously received little attention. With the advent of direct oral anticoagulants and replacement agents, the treatment and preventive management of thromboembolism have become a common challenge across all age groups and ethnic backgrounds. In the setting of advanced perinatal and pediatric medicine in Japan, the focus has remained on thrombophilia in patients with early-onset thrombosis (EOT) and clinical guidelines were established in 2024. Heritable thrombophilia is easier to understand when categorized into "high-frequency and low-risk" and "low-frequency and high-risk" variants of anticoagulant genes. The high penetrance of heritable protein C deficiency and the concurrent thromboembolic events observed in mother-child pairs with EOT during the perinatal period highlight the need for genetic counseling with appropriate treatment and preventive management. This review describes age-dependent diagnosis and management of EOT based on its molecular epidemiology in Japan, and discusses genetic counseling for family members in the precision medicine era.