Anticoagulant effects of protein C, protein S, and antithrombin levels on the protein C pathway in young children

Abstract

The protein C (PC) pathway involves physiological anticoagulant factors (PC, protein S [PS], and factor V) and performs major anticoagulant functions in adults. Variations in the overall PC pathway function due to dynamic changes in PC and PS in early childhood are poorly understood. We aimed to evaluate the contributions of PC pathway function during early childhood by administering protac (a PC activator) and measuring changes in plasma thrombin generation (TG). The correlations between anticoagulant factors and percentage of protac-induced coagulation inhibition (PiCi%) were assessed. Before protac addition, TG in newborns (n=35), infants (n=42), early children (n=35), and adults (n=20) were 525±74, 720±96, 785±53, and 802±64 mOD/min, and the PiCi% were 42.1±9.9, 69.8±11.0, 82.9±4.4, and 86.9±3.4%, respectively. The distribution of PiCi% on the two axes of TG (with or without protac) continuously changed with age and differed from that of warfarin-treated plasma or adult PC- or PS-deficient plasma. PiCi% increased dynamically during infancy and correlated with PS levels in newborns and PC levels in young children. Increment of PC or fresh frozen plasma equivalent to approximately 25% PC in PC-deficient plasma improved PiCi%. This automatic measurement requiring a small sample volume is useful for the analysis of developmental hemostasis.