Summary
The ability to generate thrombin is decreased and delayed in plasma from the healthy
newborn infant compared to the adult. Only 30 to 50% of peak adult thrombin activity
can be produced in neonatal plasma. To test whether this observation can be explained
by the low neonatal levels of the contact or vitamin K dependent factors, we measured
neonatal thrombin generation after raising the concentration of these factors to adult
values. We also determined whether the addition of a variety of blood products to
neonatal plasma improved thrombin generation. An amidolytic method was used to quantitate
intrinsic (APTT) and extrinsic (PT) pathway thrombin generation in defibrinated pooled
cord plasma from healthy term infants. Added individually, factors VII, IX, X or the
contact factors (CF) failed to alter the rate or the total amount of thrombin generated
in neonatal plasma. In contrast, the addition of prothrombin increased the total amount
of thrombin generated to above adult values in both the APTT and the PT systems but
did not alter the rate of thrombin generation. The rate of thrombin generation in
cord plasma shortened after a combination of II, IX, X and CF was added to the APTT
system or II, VII and X to the PT system. In both systems, the total amount of thrombin
generated was linearly related to the initial prothrombin concentration. Each of fresh
frozen plasma, cryoprecipitate, plasma from platelet concentrates, or factor IX concentrate
(in amounts used therapeutically) caused an increase in the total amount of thrombin
generated which was related to the increase in prothrombin concentration. Thus, the
total amount of thrombin generated in newborn plasma is critically dependent on the
prothrombin concentration whereas the rate at which thrombin is generated is dependent
on the levels of many other coagulation proteins in combination.
Keywords
Coagulation - Prothrombin - Newborn
