Bleeding and thrombosis issues in pediatric patients: current approach to diagnosis and treatment.

symptoms: cephalhematomas, injury-related bleeding and bleeding into the skin, manifesting as petechiae, purpura and ecchymoses. Persistent oozing from the umbilical stump is typical for infants with defective fi brinogen production or function and FXIII defi ciency. Joint hemarthroses, typical for severe hemophilias, rarely occur before ambulation. A small proportion of infants with severe coagulation factor defi ciencies may present with intracranial hemorrhage as the fi rst manifestation [8–10] . Laboratory variations of hemostatic tests may make it diffi cult to establish any diagnosis of bleeding disorder in infants [1–4] . Diagnostic problems of special concern are the need to adapt all coagulation assays for small amounts of blood and the age-related interpretation required for test results. The prolonged PT in neonates refl ects decreased plasma concentrations of vitamin K-dependent factors, whereas the prolonged PTT stems from decreased plasma levels of contact factors as well [2–4] . The levels of FVIII, FV and FXIII correlate well with adult boundaries. Plasma concentrations of fi brinogen may be skewed upwards, despite the fact that thrombin clotting time may be prolonged, due to a normally present ‘fetal’ fi brinogen [11] . Bleeding time is shorter in healthy neonates as compared to adults, probably because of increased concentrations and enhanced function of von Willebrand factor (VWF) and VWF large multimers [2–4, 12] , increased hematocrit and the presence of large red cells. The platelet numHemostasis is a dynamic process which begins in utero. Coagulation factors are synthesized by fetuses by 10 weeks’ gestational age and their concentrations gradually increase, being physiologically lower in premature infants as compared to full-term babies or healthy children [1–4] . In the neonate, plasma concentrations of vitamin Kdependent coagulation factors (II, VII, IX, X) and contact factors (XI, XII, prekallikrein and high-molecular-weight kininogen) are about 50% of adult values [4] . Furthermore, the capacity of newborns to generate thrombin, dependent upon plasma concentrations of procoagulants, is reduced [5, 6] . These facts, theoretically increasing the risk of severe bleeding, are balanced by the protective effects of physiological defi ciencies of the inhibitors of coagulation, as well as by the decreased fi brinolytic capacity in infants [4, 7] . In this special issue Chan and his colleagues discuss the phenomenon of reduced plasmin generation in neonates as compared to adults and the lower inhibitory antifi brinolytic effect of lipoprotein on neonatal as compared to adult plasma. The latter may stem from physiologically reduced plasminogen concentrations. Decreased neonatal fi brinolysis potentially increases the risk of perinatal thrombosis, which may require the use of thrombolytic therapy. The clinical presentation of bleeding disorders in infants is characterized by one or more of the following