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A defect of platelet aggregation associated with an abnormal distribution
of glycoprotein IIb-IIIa complexes within the platelet: the cause of a
lifelong bleeding disorder
R Hardisty, D Pidard, A Cox, T Nokes, C Legrand, C Bouillot, A Pannocchia, E Heilmann, P Hourdille and S Bellucci
Institute of Child Health, London, England.
A young Italian man (A.P.) has a lifelong history of bleeding from gums and
mucocutaneous tissue. Electron microscopy showed a wide diversity of
platelet size including giant forms. In citrated platelet-rich plasma
(PRP), platelet aggregation induced by adenosine diphosphate (ADP) and
other agonists was much reduced. Both secretion and clot retraction were
normal. The aggregation of washed platelets with ADP was improved but
remained subnormal, as was aggregation with collagen and thrombin.
Fibrinogen-binding was analyzed by flow cytometry using platelets in whole
blood or PRP and was markedly decreased. Crossed immunoelectrophoresis of
Triton X-100 extracts of (A.P.) platelets showed that GP IIb-IIIa levels
were 40% to 50% of normal. Glycoprotein (GP) IIb and GP IIIa were of usual
migration in sodium dodecyl sulfate- polyacrylamide gel electrophoresis,
but their labeling was much reduced during lactoperoxidase-catalyzed
iodination. Binding to (A.P.) platelets of four different 125I-labeled
monoclonal antibodies to GP IIb-IIIa complexes was reduced to 12% to 20% of
normal levels. However, when the patient's platelets were stimulated with
alpha-thrombin, monoclonal antibody binding showed the same increase
(approximately 20,000 sites) as normal platelets. Both flow cytometry and
immunocytochemical studies showed that the distribution of residual surface
GP IIb-IIIa within the total (A.P.) platelet population was heterogeneous
and not related to platelet size. Staining of ultrathin sections confirmed
the presence of an internal pool of GP IIb-IIIa. Monoclonal antibodies to
other membrane glycoproteins bound normally to (A.P.) platelets. The
patient has a selective deficiency of the surface pool of GP IIb-IIIa
complexes that is manifested clinically by a mild Glanzmann's
thrombasthenia-like syndrome.
Volume 80,
Issue 3,
pp. 696-708,
08/01/1992
Copyright © 1992 by The American Society of Hematology
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