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HJ Hassan, A Leonardi, C Chelucci, G Mattia, G Macioce, R Guerriero, G Russo, PM Mannucci and C Peschle
Department of Hematology-Oncology, Istituto Superiore di Sanita, Rome,
Italy.
The expression of a number of blood coagulation factors (F) (FX, FIX,
FVIII, FVII, alpha-, beta-, gamma-fibrinogen chains, protein C, and
antithrombin III [AT III]) was analyzed at RNA and protein level in 5- to
10-week-old human embryos and fetuses. FX, FIX, and FVII were also analyzed
at protein level. Total and poly(A)+ RNA, extracted from embryonic-fetal
(FL) and adult liver (AL), were analyzed by dot and Northern blot
hybridization with specific cDNA probes. The results indicate that: (1) the
size of the messenger RNAs of these factors is equivalent in FL and AL; (2)
in the 5- to 10-week period, their abundance in FL increases from 30% to
50% of the adult level except for FIX (from 2% to 10%) and FX (always 100%
of the adult value). Western blot analysis of FIX, FX, and FVII in 5- to
10-week soluble liver proteins and 6- to 8-week plasma showed a low level
of FIX versus a higher concentration of both FVII and FX, when compared
with corresponding adult values, ie, a liver protein level of 10% versus
100% and a plasma concentration level of 10% versus 40%. Although little is
known so far on the activity and the functional role of the clotting
factors in early human ontogenic development, these studies suggest an
activation of FX via the FVII/tissue factor activity rather than the
FIXa/FVIIIa phospholipid complex in human embryonic and early fetal life.
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