title: The unique immunological features of heparin-induced thrombocytopenia.
abstract: Heparin-induced thrombocytopenia (HIT) is a serious drug reaction that leads to a decrease in platelet count and a high risk of thrombosis. HIT patients produce pathogenic immunoglobulin G (IgG) antibodies that bind to complexes of platelet factor-4 (PF4) and heparin. HIT immune complexes crosslink Fc-receptors resulting in platelet and monocyte activation. These events lead to the release of procoagulant chemokines and tissue factor, which together create an intensely prothrombotic state. HIT represents an atypical immune response because it has features of both T cell-dependent and T cell-independent mechanisms. The disorder is characterized by newly formed anti-PF4/heparin IgG antibodies, which are characteristic of a T cell-dependent mechanism; however, re-exposure to heparin, months after HIT, does not lead to a memory response, which is consistent with a T cell-independent mechanism. In this review, we discuss the immunobiological events that can explain these features, including the role for T cell-dependent and T cell-independent mechanisms in HIT antibody generation, the immunogenic characteristics of the PF4/heparin antigen, and the concept of a temporary loss in immune regulation contributing to the onset of HIT. We also present a novel immunobiological model to explain the atypical immune response that is characteristic of HIT.
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Phillip
authors.identifier: 0000-0002-9095-9543
authors.initials: P
authors.lastname: Staibano
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.|Canadian Blood Services, Hamilton, ON, Canada.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Arnold
authors.affiliation: McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
authors.forename: Dawn M E
authors.initials: DM
authors.lastname: Bowdish
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Ishac
authors.identifier: 0000-0002-5695-4343
authors.initials: I
authors.lastname: Nazy
mesh_terms: D000818:Animals; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology*
chemical_list: D006493:Heparin
keywords: T cells; antibodies; heparin-induced thrombocytopenia; immunology; platelet factor 4