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Direct detection of activated platelets and platelet-derived microparticles
in humans
CS Abrams, N Ellison, AZ Budzynski and SJ Shattil
Department of Medicine, University of Pennsylvania School of Medicine,
Philadelphia 19104.
Flow cytometry was used to determine whether activated platelets and
platelet-derived microparticles can be detected directly in whole blood
after a hemostatic insult. Two different in vivo models of platelet
activation were examined: (1) a standardized bleeding time, and (2)
cardiopulmonary bypass. Platelets and microplatelets were identified with a
biotinylated anti-glycoprotein (GP)lb antibody and a fluorophore,
phycoerythrin-streptavidin. Microparticles were distinguished from
platelets by light scatter. Activated platelets were detected with three
fluorescein-labeled monoclonal antibodies (MoAbs): (1) PAC1, which binds to
the activated form of GPIIb-IIIa; (2) 9F9, a newly developed antibody that
is specific for fibrinogen bound to the surface of activated platelets; and
(3) S12, which binds to an alpha- granule membrane protein expressed on the
platelet surface after granule secretion. In nine normal subjects, bleeding
times ranged from 4.5 to 7.5 minutes. Over this time, there was a
progressive increase in the amount of PAC1, 9F9, and S12 bound to platelets
in blood emerging from the bleeding time wound. With all three antibodies,
platelet activation was apparent as early as 30 seconds after the incision
(P less than .03). Activation was accompanied by a progressive decrease in
the concentration of platelets in blood from the wound, while the
concentration of microparticles increased slightly. In nine patients
undergoing open heart surgery, 1 hour of cardiopulmonary bypass caused a
2.2-fold increase in the relative proportion of microparticles in
circulating blood (P less than .001). Moreover, bypass caused platelet
activation as evidenced by a mean two- to threefold increase in PAC1
binding to platelets. Although this increase was significant (P less than
.02), PAC1 binding exceeded the normal range for unstimulated control
platelets in only 5 of 9 patients, and 9F9 and S12 binding exceeded the
normal range in only two patients. Taken together, these studies
demonstrate that it is now feasible using flow cytometry to evaluate the
extent of platelet activation and the presence of platelet- derived
microparticles in the circulation of humans.
Volume 75,
Issue 1,
pp. 128-138,
01/01/1990
Copyright © 1990 by The American Society of Hematology
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