Submitted June 15, 2005
Accepted March 22, 2006
Relative efficacy of intravenous immunoglobulin G in
ameliorating thrombocytopenia induced by anti-platelet
GPIIbIIIa versus GPIb
antibodies
Michelle Lee Webster, Ebrahim Sayeh, Min Crow, Pingguo Chen, Bernhard Nieswandt, John Freedman, and Heyu Ni*
The Canadian Blood Services, and St. Michael's Hospital, University of Toronto
Institute of Clinical Biochemistry and Pathobiochemistry, and Rudolf Virchow Center for Experimental
Toronto Platelet Immunobiology Group and Department of Laboratory Medicine, St. Michael's Hospital
* Corresponding author; email: nih{at}smh.toronto.on.ca.
Intravenous immunoglobulin G (IVIG) is used to treat
idiopathic thrombocytopenic purpura (ITP). While many
patients benefit from IVIG, some are refractory to this
therapy. ITP is characterized by platelet clearance
mediated primarily by anti-platelet antibodies against
GPIIbIIIa and/or the GPIb
complex. These two
groups of antibodies may induce ITP through different
mechanisms. We tested the hypothesis that IVIG may not
be equally effective in preventing ITP caused by anti-
GPIIbIIIa versus anti-GPIb antibodies in mice.
Thrombocytopenia was induced in BALB/c mice using
monoclonal antibodies against either mouse GPIIbIIIa
(JON1, JON2, and JON3) or GPIb (p0p3, p0p4,
p0p5, p0p9, and p0p11). Pre-treatment with IVIG
significantly ameliorated ITP in all anti-GPIIbIIIa-
injected animals. Conversely, IVIG failed to prevent
ITP in all anti-GPIb-treated mice, except for
p0p4. These results were repeated in C57BL/6 mice, and
with different IVIG preparations. These data in mice suggest that patients with ITP mediated by anti-GPIb antibodies may be less responsive to IVIG treatment.
