Autoantibodies in Heparin-Induced Thrombocytopenia
Heparin-induced thrombocytopenia (HIT) is a common and clinically important autoimmune disease in which antibodies to complexes of platelet factor 4 (PF4) and heparin cause platelet activation, thrombocytopenia, and predisposition to thrombosis. HIT provides a model of autoimmunity in which a heterologous GAG combines with a normal endogenous protein that is released from platelets in specific clinical settings to generate autoantibodies in a high percentage of otherwise immunologically normal individuals. A subset of seropositive individuals develops thrombocytopenia and is at risk for life-threatening thrombotic complications. Recent studies using recombinant proteins and murine models have provided insights into mechanisms governing PF4/heparin antigenicity, autoantibody development, and thrombotic injury.
