Developmental hemostasis and its relevance to pediatric thrombosis

The coagulation system of neonates and children evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins between children of different age groups and adults.This concept is known as “developmental hemostasis” and it is well recognized internationally.

Developmental hemostasis has important biological and clinical implications. Coagulation factors are synthesized by the fetus and begin to appear at 10 weeks’ gestation and their levels are lower in premature infants compared to full-term babies and healthy children. The hemostatic system, however, is balanced by the protective effects of physiologic deficiencies of the inhibitors of coagulation, as well as by the decreased fibrinolytic capacity in infants.

Since developmental hemostasis has important biological and clinical implications, laboratory test results should always be compared to age-related reference intervals, in order to avoid misclassifications of “healthy”, or prone to “bleeding” or “thrombosis” at any given age. Overall, impaired platelet function, along with physiologic deficiency of coagulation factors in otherwise healthy neonates may yield poorer clot firmness, in correlation with gestational age. None the less, high activity of VWF and low levels of coagulation inhibitors, counterbalance the newly formed, delicate, hemostatic system. This system, however, has little reserve capacity; thus preterm babies or sick infants are extremely vulnerable and predisposed to hemorrhagic or thrombotic complications.

The most commonly reported venous thromboembolisms (VTEs) in neonates are renal vein thrombosis (the presenting symptom of which may be hematuria in association with thrombocytopenia), vena caval occlusion, and thromboembolic stroke mainly of venous origin. Additional perinatal and neonatal locations of childhood VTEs are cerebral venous thrombosis and portal or mesenteric vein thrombosis. Purpura fulminans, a life-threatening event characterized histologically by microvascular thromboses in the dermis followed by perivascular hemorrhage and skin necrosis, has been reported in neonates with congenital absence of protein C or protein S, or the presence of a homozygous F5 mutation (FVleiden).

Thrombosis in children is gaining increasing awareness as advanced medical care increases treatment intensity of hospitalized pediatric patients. Among pediatric patients, children with cancer, especially those who have Central lines, may be highly susceptible for thrombotic complications. Guidelines for the diagnosis and treatment of children and neonates with thrombosis are mostly extrapolated from adult data, despite the uniqueness of their hemostatic system.

This special issue of ICHTIC magazine will focus upon challenging issues dealing with children with cancer and thrombosis, the potential role of thrombophilic risk factors and current and future treatments.

References