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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1694-1702
Surface expression and functional characterization of  -granule
factor V in human platelets: effects of ionophore A23187, thrombin,
collagen, and convulxin
L. Alberio,
O. Safa,
K. J. Clemetson,
C.
T. Esmon, and
G. L. Dale
From the W. K. Warren Medical Research Institute and Department of
Medicine, University of Oklahoma Health Sciences Center; the
Cardiovascular Biology Research Program, Oklahoma Medical Research
Foundation, and Howard Hughes Medical Institute, Oklahoma City, OK; and
Theodor Kocher Institute, University of Berne, Switzerland.
Factor V (FV) present in platelet  -granules has a significant but
incompletely understood role in hemostasis. This report demonstrates
that a fraction of platelets express very high levels of surface-bound,
-granule FV on simultaneous activation with 2 agonists, thrombin and
convulxin, an activator of the collagen receptor glycoprotein VI. This
subpopulation of activated platelets represents 30.7% ± 4.7% of
the total population and is referred to as convulxin and
thrombin-induced-FV (COAT-FV) platelets. COAT-FV platelets are also
observed on activation with thrombin plus collagen types I, V, or VI,
but not with type III. No single agonist examined was able to produce
COAT-FV platelets, although ionophore A23187 in conjunction with either
thrombin or convulxin did generate this population. COAT-FV platelets
bound annexin-V, indicating exposure of aminophospholipids and were
enriched in young platelets as identified by the binding of thiazole
orange. The functional significance of COAT-FV platelets was
investigated by demonstrating that factor Xa preferentially bound to
COAT-FV platelets, that COAT-FV platelets had more FV activity than
either thrombin or A23187-activated platelets, and that COAT-FV
platelets were capable of generating more prothrombinase activity than
any other physiologic agonist examined. Microparticle production by
dual stimulation with thrombin and convulxin was less than that
observed with A23187, indicating that microparticles were not
responsible for all the activities observed. These data demonstrate a
new procoagulant component produced from dual stimulation of platelets
with thrombin and collagen. COAT-FV platelets may explain the unique
role of -granule FV and the hemostatic effectiveness of young platelets.
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