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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2087-2093
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Effects of intravenous immunoglobulin on platelet count and
antiplatelet antibody disposition in a rat model of immune
thrombocytopenia
Ryan J. Hansen and
Joseph
P. Balthasar
From the Department of Pharmaceutical Sciences,
University at Buffalo, The State University of New York, Buffalo.
Experiments were conducted to investigate the effects of
intravenous immunoglobulin (IVIG) in a rat model of immune
thrombocytopenia (ITP). Rats were pretreated with 0 to 2 g/kg IVIG and
then challenged with an antiplatelet antibody (7E3, 8 mg/kg). IVIG
effects on 7E3-induced thrombocytopenia and on 7E3 pharmacokinetics
were determined. IVIG pretreatment led to significant changes in the degree and time-course of 7E3-induced thrombocytopenia
(P = .031). Nadir percent platelet counts were 121% to
279% greater in animals treated with IVIG (0.4-2 g/kg) than in animals
receiving 7E3 alone. IVIG treatment also led to dose-dependent
increases in 7E3 clearance (P < .001), with more than
2-fold increases in 7E3 clearance seen following the highest dose of
IVIG. In vitro experiments showed that IVIG effects on platelet count
are not likely due to anti-idiotypic inhibition of 7E3-platelet binding
and that IVIG did not directly bind to 7E3. Consequently, IVIG-7E3
binding cannot explain the increase of 7E3 clearance following IVIG
treatment. We propose that the observed increase in 7E3 clearance with
IVIG therapy is due to saturation of the FcRn salvage receptor for IgG.
The importance of the effect of IVIG on 7E3 clearance to the prevention of thrombocytopenia in these animals is unclear at present;
nonetheless, these data provide experimental support for a new
mechanism of IVIG action in ITP (ie, IVIG-mediated increases in
antiplatelet antibody elimination). This model of ITP will be useful
for further investigations of IVIG mechanism of action and for
development of new therapies for ITP.
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