Properties of factor VIIa/tissue factor complexes in an umbilical vein
model
FE Almus, LV Rao, RA Fleck and SI Rapaport
Department of Medicine, University of California, San Diego, La Jolla
92093.
An umbilical vein model was designed in which washed vein segments are
filled with a reaction mixture containing factor VIIa, Ca(+)+, and a
substrate, either 3H-factor IX or 3H-factor X. The vein wall provides the
tissue factor (TF) for factor VIIa/TF complexes that activate the
substrates as measured by activation peptide release. The model was
developed to study TF induced on venous endothelium in situ. However,
unlike previous studies with TF expressed on cultured umbilical vein
endothelial cells, factors IX and X were activated without first having to
expose the vein wall to a perturbing stimulus. Histologic studies revealed
that washing the vein and mixing the reaction mixture before subsampling
had disrupted the endothelium. Immunostaining with anti-TF antibodies
revealed no staining of endothelium but intense staining in extensions of
Wharton's jelly penetrating fenestrations of the muscularis media of the
vein. Thus, the model provided data on factor VIIa/TF formed, not on
endothelium, but within the mucoid connective tissue of Wharton's jelly. It
is known that factor VIIa/TF formed with TF in suspension or with TF
expressed on the surface of cultured cells activates factor X more rapidly
than factor IX. In contrast, in the umbilical vein model, when each
substrate was present in an 88 nmol/L concentration, factors IX and X were
activated at equivalent rates (mean activation rate for factor IX, 18.8 +/-
3.6 nmol/L/h; for factor X, 17.8 +/- 2.9 nmol/L/h; n = 9 paired vein
segments). These data strengthen the evidence that factor VIIa/TF
activation of factor IX represents a key initial reaction of coagulation in
tissues. These results also show that data obtained with factor VIIa/TF
complexes formed on the surface of cultured cells need not hold for factor
VIIa/TF complexes formed in extracellular matrix.
Volume 76,
Issue 2,
pp. 354-360,
07/15/1990
Copyright © 1990 by The American Society of Hematology
