Clinical implications of genetic testing for congenital protein C deficiency in pregnancy

Congenital protein C (PC) deficiency is a mostly autosomal dominant hereditary thrombophilia associated with early onset arterial and venous thrombotic diseases. In newborns, PC deficiency results in severe complications such as cerebral hemorrhage, cerebral infarction, and purpura fulminans, leading to death in some cases. We report two cases of deep vein thrombosis diagnosed during pregnancy that prompted genetic testing confirming definitive congenital PC deficiency. One patient with deep vein thrombosis at 30 weeks of gestation underwent anticoagulation therapy with the placement of an inferior vena cava filter. Genetic testing revealed a missense mutation in the PC gene. Another patient developed deep vein thrombosis at 9 weeks of gestation and received anticoagulant therapy, revealing a frameshift mutation in the gene. Genetic testing confirming congenital PC deficiency facilitates tailored postpartum management, including long-term anticoagulation therapy, based on the mother's thrombosis risk. For newborns, early diagnosis allows timely preparation of treatments, such as freshly thawed frozen plasma or PC replacement therapy and ensures closer monitoring through imaging evaluations, enabling early intervention to decrease the severity of potential complications. Given its utility in managing maternal and neonatal outcomes, early genetic testing in suspected cases of maternal PC deficiency is crucial before delivery.