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Heparin-induced thrombocytopenia: laboratory studies
JG Kelton, D Sheridan, A Santos, J Smith, K Steeves, C Smith, C Brown and WG Murphy
Department of Medicine, McMaster University Medical Centre, Hamilton,
Ontario, Canada.
This report describes studies into the pathophysiology of heparin- induced
thrombocytopenia. The IgG fraction from each of nine patients with
heparin-induced thrombocytopenia caused heparin-dependent platelet release
of radiolabeled serotonin. Both the Fc and the Fab portions of the IgG
molecule were required for the platelet reactivity. The platelet release
reaction could be inhibited by the Fc portion of normal human or goat IgG,
and patient F(ab')2, but not F(ab')2 from healthy controls. These results
suggested that the Fab portion of IgG binds to heparin forming an immune
complex and the immune complexes initiate the platelet release reaction by
binding to the platelet Fc receptors. To directly challenge this
hypothesis, we preincubated the serotonin-labeled platelets with the
monoclonal antibody against the platelet Fc receptor (IV.3). This
monoclonal antibody completely inhibited the release reaction caused by
heparin and patient sera, as well as heat aggregated IgG, but did not block
collagen or thrombin- induced platelet release. Heparin-dependent platelet
release also could be inhibited in vitro by the addition of monocytes and
neutrophils, but not by red cells, presumably because the Fc receptors on
the phagocytic cells have a higher binding affinity for IgG complexes than
do platelets. Platelets from patients with congenital deficiencies of
specific glycoproteins Ib and IX (Bernard-Soulier syndrome) and IIb and
IIIa (Glanzmann's thrombasthenia) displayed normal heparin-dependent
release indicating that the release reaction did not require the
participation of these glycoproteins. These studies indicate that
heparin-induced thrombocytopenia is an IgG-heparin immune complex disorder
involving both the Fab and Fc portion of the IgG molecule.
Volume 72,
Issue 3,
pp. 925-930,
09/01/1988
Copyright © 1988 by The American Society of Hematology
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