Platelet and leukocyte Fcγ receptors in heparin-induced thrombocytopenia

INTRODUCTION Heparin-induced thrombocytopenia (HIT) is a unique immune-mediated disorder. The central paradigm is that HIT is caused by IgG that produces strong platelet activation via interaction with platelet FcγIIa receptors (FcγRIIa). HIT is relatively common, occurring in as many as 5% of certain heparin-treated patient populations. Affected patients have thrombocytopenia, often develop a paradoxical thrombotic episode, with timing consistent with heparin being the causal agent, and without any other obvious cause (Lo et al., 2006). One possible reason for the unique clinical profi le is the central role that platelet FcγRIIa plays in mediating platelet activation in HIT. Indirect evidence suggests a crucial role for platelet activation in the pathogenesis of HIT because thrombocytopenia and the presence of HIT antibodies are strongly associated with thrombosis, whereas the formation of antibodies without thrombocytopenia is not (Warkentin et al., 1995). Notwithstanding the role that platelet FcγRIIa plays in platelet activation, leukocyte FcγRs may also contribute to the pathogenesis of HIT (Xiao et al., 2008).