Autoantibodies in heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia and thrombosis (HITT) is a common and clinically important autoimmune disease in which antibodies to complexes between heparin and platelet factor 4 (PF4) cause platelet activation, thrombocytopenia and thrombosis. HITT provides a model of autoimmunity in which a heterologous glycosaminoglycan 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. The pathogenic relevance of anti-PF4/heparin antibodies is supported by their presence in almost all affected individuals, such as, by their capacity to recapitulate the salient features of the disease in animal models. Laboratory methods to support the diagnosis of HIT fall into two broad categories: assays that measure platelet function and antigen-based tests. The serotonin release assay (SRA) and platelet aggregation using washed platelets have been judged as having comparable sensitivity and specificity. Aggregometry using platelet-rich plasma is less reliable. The sensitivity and specificity of flow cytometric analysis of platelet activation or microparticle release has not been well studied. The utility of fluid phase and rapid gel-card assays compared with existing enzyme-linked immunosorbent assay (ELISAs) is under investigation.
