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Fc gamma RIIA H/R 131 polymorphism, subclass-specific IgG anti-
heparin/platelet factor 4 antibodies and clinical course in patients with
heparin-induced thrombocytopenia and thrombosis
G Arepally, SE McKenzie, XM Jiang, M Poncz and DB Cines
Department of Medicine, University of Pennsylvania, Philadelphia 19104,
USA.
The explanation why only a subset of patients with heparin-induced
thrombocytopenia (HIT) develop clinically apparent thromboses (HITT)
remains uncertain. It has been proposed that platelet activation induced by
cross-linking of Fc gamma RIIA by anti-heparin/platelet factor 4 (PF4)
antibodies is central to the pathogenesis of thrombosis. The observation
that a common functional polymorphism of Fc gamma RIIA, involving either an
arginine (R) or histidine (H) at amino acid 131, may underlie disease
susceptibility prompted us to investigate the prevalence of receptor
isoforms in patients with HIT and HITT. Furthermore, because these isoforms
reportedly differ in their avidity for immune complexes containing human
IgG2, we also analyzed sera from patients with HIT and HITT for the
prevalence of various subclass- specific IgG anti-heparin/PF4 antibodies.
No difference in the allele frequency of Fc gamma RIIA-H131 or R131 was
identified among 13 patients with HIT or 23 with HITT compared with 102
controls (chi 2 = 1.21, P = .8). Furthermore, although most patients had
IgG2 antibodies (62%), IgG, was the predominant subclass in 30 of the 34
patients with IgG anti-heparin/PF4 antibodies and in 12 was the exclusive
subclass found. Also, there was no association between the concordance of
IgG2 anti-heparin/ PF4 antibodies and the expression of Fc gamma RIIA-H131
in patients with HITT compared with patients with thrombocytopenia alone.
These results make it unlikely that the Fc gamma RIIA-H131 isoform or IgG2
anti-heparin/PF4 antibodies are required to develop HITT, suggesting that
factors in addition to cross-linking of Fc gamma RIIA receptors contribute
to the pathogenesis of thrombosis in patients with heparin-dependent
antiplatelet: antibodies.
Volume 89,
Issue 2,
pp. 370-375,
01/15/1997
Copyright © 1997 by The American Society of Hematology
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