The prototype immune thrombocytopenia is (auto)immune thrombocytopenic purpura, ITP.
The major issues in the pathophysiology, diagnosis, and therapy of ITP are presented.
Mouse models of the pathophysiology of ITP have allowed greater understanding of the
role of antiplatelet antibodies and of antibody effector mechanisms. In addition,
there has been a substantial increase in interest in the use of mouse models to understand
the mechanisms of action of therapeutics for ITP, with notable progress for intravenous
immunoglobulin (IVIG) and anti-red blood cell therapies. The immune-mediated thrombocytopenia
and thrombosis syndromes are a common cause of morbidity and mortality; the prototype
is heparin-induced thrombocytopenia and thrombosis (HITT). There has been substantial
progress in understanding the pathophysiology, diagnosis, and therapy of HITT in the
last decade, but there remain major questions. The four necessary and sufficient elements
for HITT in vivo were established in our mouse model (namely platelet factor 4 [PF4],
heparin, antibody to the heparin/PF4 complex, and platelet Fc receptor for immunoglobulin
G [FcγRIIa]). Currently, our HITT mouse models are being used to address a number
of questions. For example, what are the roles of antibody titer, isotype, and epitope
targets? Are there genetic determinants of platelet activation, such as the platelet
FcγRIIa receptor density, operable in HITT? What are the roles of tissue factor/factor
VIIa (TF/VIIa), monocytes, and blood cell-derived microparticles? What is the contribution
of pre-existing endothelial cell (EC) dysfunction, and/or induced EC dysfunction?
As in many human disorders, preclinical mouse models will continue to be important
in the immune thrombocytopenia syndromes to achieve translation into improved patient
care.
KEYWORDS
Immune thrombocytopenia - ITP - antiplatelet antibodies - heparin-induced thrombocytopenia/thrombosis
- HITT - mouse models
REFERENCES
in vitro
.
Blood.
2003;
102
887-895
steven.mckenzie@mail.tju.edu
