Low Arterial Saturation Is Associated With Increased Sensitivity to Activated Protein C in Children With Congenital Heart Disease

Objectives: Children with congenital heart disease experience both hemorrhagic and thrombotic complications. In this report the authors test the hypothesis that hypoxemia is associated with altered sensitivity to activated protein C (aPC) in pediatric patients with congenital heart lesions.Design: A retrospective genetic registry review, with statistical evaluation of factors contributing to the aPC ratio.Setting: Large university hospital.Participants: Cohort of 92 children with congenital heart disease undergoing cardiac catheterization procedures.Interventions: The authors measured the aPC ratio at cardiac catheterization and evaluated the contribution of independent variables using linear regression and classification tree approaches. Independent variables included age, gender, use of aspirin, history of thrombosis, room air arterial saturation, factor VIII:C levels, presence of congestive heart failure, and heterozygosity for factor V Leiden.Measurements and Main Results: At univariate analysis, factor V Leiden, female gender, room air arterial saturation, age greater than 6 months, and plasma factor VIII:C levels were associated with a lower aPC ratio (resistance to aPC). At stepwise linear regression, arterial saturation, factor VIII:C level, female gender, and factor V Leiden were independently associated with a lower aPC ratio, and these variables explained about 49% of the variability in aPC ratio. The classification tree approach confirmed the dependence of aPC ratio on factor V genotype and arterial saturation.Conclusions: The aPC ratio in this population is associated with hypoxemia, independent of factors previously observed in adults. Further studies are under way to determine how aPC resistance or sensitivity may independently affect perioperative hemostasis in this population.