Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor.
BACKGROUND
Bleeding in hemophilic neonates has a low incidence. A possible explanation for this could be the peculiarities of the neonatal hemostatic system, especially low levels of the inhibitors tissue factor pathway inhibitor (TFPI) and antithrombin (AT).


OBJECTIVE
We investigated the influence of an elevation of these inhibitors to adult levels on the thrombin generation (TG) in normal neonatal plasma and factor (F) VIII-depleted neonatal plasma by means of incubation with anti-FVIII-antibodies.


METHODS
TG was measured after activation with low amounts of tissue factor (TF) by using Calibrated Automated Thrombography.


RESULTS
TG in FVIII-depleted neonatal plasma was nearly as high as in normal neonatal plasma. TG decreased after elevation of AT in both neonatal plasmas. After elevation of TFPI TG decreased much more in FVIII-depleted neonatal plasma than in normal neonatal plasma. After elevation of both inhibitors their synergistic effect led to a stronger decrease of TG in FVIII-depleted neonatal plasma. TG measured in plasma of one hemophilic newborn showed the same pattern as in FVIII-depleted neonatal plasma.


CONCLUSIONS
Our observation provides a biochemical basis for the rare bleeding in hemophilic neonates and shows the important role of the natural inhibitors in the hemostatic system of hemophilic patients.
Fritsch
P
P
Department of Pediatrics, Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Medical University of Graz, Auenbruggerplatz 30, 8036 Graz, Germany.
Cvirn
G
G
Cimenti
C
C
Baier
K
K
Gallistl
S
S
Koestenberger
M
M
Roschitz
B
B
Leschnik
B
B
Muntean
W
W
D000328:Adult; D000991:Antithrombins / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008074:Lipoproteins / Q000097:blood*; D010949:Plasma; D013917:Thrombin / Q000096:biosynthesis*
D000991:Antithrombins; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005169:Factor VIII; D013917:Thrombin