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Platelet adhesion and thrombus formation on subendothelium in platelets
deficient in glycoproteins IIb-IIIa, Ib, and storage granules
HJ Weiss, VT Turitto and HR Baumgartner
Patients whose platelets are deficient in glycoprotein (GP) Ib, IIb- IIIa
(thrombasthenia), or granule substances (storage pool deficiency, SPD) were
studied to define further the properties of platelets that mediate platelet
adhesion and thrombus formation on subendothelium. Both nonanticoagulated
and citrated blood were exposed to everted, de- endothelialized rabbit
vessel segments under controlled flow conditions and shear rates varying
from 650 to 3,300 sec-1. Morphometry was used to measure platelet thrombus
dimensions and the percentage of the subendothelial surface covered with
contact (C) or spread (S) platelets. Adhesion was defined as C + S. The
results in SPD demonstrated (1) reduced thrombus dimensions in delta-SPD
(pure dense granule deficiency) in proportion to the magnitude of the dense
granule defect; (2) an even greater reduction in thrombus dimensions in
patients with combined deficiencies of alpha and dense granules (alpha
delta-SPD); and (3) impaired platelet adhesion at several conditions in
alpha delta-SPD and, in delta-SPD, a hematocrit-dependent impairment of
adhesion in citrated blood at 2,600 sec-1. In thrombasthenia, platelets
were present as a monolayer on the subendothelial surface in both
nonanticoagulated and citrated blood, indicating an absolute requirement
for GPIIb-IIIa in promoting platelet-platelet interaction at all shear
rates and perfusion times. Two types of abnormalities in platelet-vessel
wall interactions were observed. In nonanticoagulated blood, the percentage
of platelets in the C phase was consistently increased at all shear rates,
but C + S values were normal. These observations indicate that platelets
deficient in GPIIb-IIIa do not spread normally on the subendothelial
surface exposed to nonanticoagulated blood. With citrated blood, the C + S
value in thrombasthenia was reduced at both 800 and 2,600 sec-1, as in von
Willebrand's disease, and a similar degree of reduction (about 50%) was
observed in normal blood treated with a monoclonal antibody to GPIIb- IIIa.
The findings, together with theoretical considerations, are consistent with
an hypothesis that GPIIb-IIIa mediates the spreading of platelets on
subendothelium following the initial attachment through GPIb and that
GPIIb-IIIa may be considered an adhesion site on the platelet membrane.
Abnormalities of GPIIb-IIIa may, depending on the conditions of study,
result in either increased values of C platelets or decreased values of C +
S. The results of the study further suggest that a complex interaction of
platelet granule factors and membrane GP mediate platelet adhesion and
thrombus formation.
Volume 67,
Issue 2,
pp. 322-330,
02/01/1986
Copyright © 1986 by The American Society of Hematology

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