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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 182-187
Heparin-induced thrombocytopenia: new evidence for the dynamic
binding of purified anti-PF4-heparin antibodies to platelets and
the resultant platelet activation
Peter M. Newman and
Beng H. Chong
From the Centre for Thrombosis and Vascular Research, Prince of
Wales Hospital, Sydney, New South Wales, Australia.
Immune heparin-induced thrombocytopenia (HIT) is associated with
antibodies directed against a complex of platelet factor 4 (PF4) and
heparin. We were able to affinity purify anti-PF4-heparin IgG (HIT
IgG) from the plasma of 2 patients with HIT. Under conditions that were
more physiological and sensitive than those in previous studies, we
observed that this HIT IgG caused platelet aggregation on the addition
of heparin. Platelets activated with HIT IgG increased their release
and surface expression of PF4. We quantitated, for the first time, the
binding of affinity-purified HIT iodine 125-IgG to platelets as they
activated in a plasma milieu. Binding of the HIT IgG was dependent on
heparin and required some degree of platelet activation. Blocking the
platelet Fc RII with the monoclonal antibody IV.3 did not prevent HIT
IgG binding to activated platelets. We concluded that anti-PF4-heparin
IgG is the component in these HIT plasmas that induces platelet
aggregation. The Fab region of HIT IgG binds to PF4-heparin on the
surface of activated platelets. We propose that only then does the Fc
portion of the bound IgG further activate the same or adjacent
platelets through the Fc receptor. Our data support a dynamic model of
platelet activation in which released PF4 enhances further antibody
binding and more release.
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