[PS3-1C-3] Heritable protein C deficiency in pediatric stroke and thrombosis
Stroke has been increasingly recognized in infants and children. The underlying conditions include surgery, infection, inflammatory disease, cardiovascular anomaly, and malignancy. Inherited thrombophilia also raises the risk of stroke, while the prevalence depends on the age and ethnicity of population. Pediatric patients with stroke are usually screened for heritable hypercoagulability. Heterozygous protein C (PC), protein S (PS) or antithrombin (AT)-deficient adults are at a higher risk of venous thrombosis than factor V Leiden or factor II G20210A carriers. Both variants of coagulation factors are the leading causes of inherited thrombophilia in Caucasian, but not, in Asian ancestries. The anticoagulant deficiency thus greatly contributes to thromboembolic events in Asian patients.
We have reported that PC-deficiency is the leading genetic cause of thrombosis in Japanese children. The majority of cases presented intracranial infarction and/or hemorrhage followed by purpura fulminans in newborns, or infection-triggered thrombosis in infancy and adolescence. Of newly identified 50 PC-deficient pediatric patients, half of them presented during the early neonatal period. Forty% of all patients harbored double and single allele mutation(s) of PROC in half and half, respectively. For the screening of newborn patients, <10% of plasma PC activity and <0.35 of PC/PS activity ratio effectively discriminated PROC mutants from non-mutants. The genotype of double-PROC mutations differed between the newborn-onset and the late-onset of disease. Neonatal cerebrovascular events are a target of genetic screening for PC-deficiency. Further study on PC-deficiency in Asian children would provide more information about the early diagnosis, management, and prophylaxis for pediatric stroke.
We have reported that PC-deficiency is the leading genetic cause of thrombosis in Japanese children. The majority of cases presented intracranial infarction and/or hemorrhage followed by purpura fulminans in newborns, or infection-triggered thrombosis in infancy and adolescence. Of newly identified 50 PC-deficient pediatric patients, half of them presented during the early neonatal period. Forty% of all patients harbored double and single allele mutation(s) of PROC in half and half, respectively. For the screening of newborn patients, <10% of plasma PC activity and <0.35 of PC/PS activity ratio effectively discriminated PROC mutants from non-mutants. The genotype of double-PROC mutations differed between the newborn-onset and the late-onset of disease. Neonatal cerebrovascular events are a target of genetic screening for PC-deficiency. Further study on PC-deficiency in Asian children would provide more information about the early diagnosis, management, and prophylaxis for pediatric stroke.