Antigens involved in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT), a common side effect of heparin therapy, can be life-threatening. Following treatment with heparin, platelet factor 4 (PF4) is released into the circulation. Heparin can bind to PF4 to form a reactive antigen on the platelet. The formation of large heparin-PF4 (H-PF4) complexes that can react with HIT antibodies depends on the concentrations of heparin and PF4. Antibodies involved in HIT are usually of the IgG class, but can be IgA or IgM; Fab and Fc fragments are necessary for the activation of platelets. In a minority of cases of HIT, antibodies to H-PF4 are not present, but antibodies to other cytokines have been found. These antibodies frequently react either with interleukin-8 (IL-8) or with neutrophil-activating peptide 2 (NAP-2). Discontinuation of heparin has been the traditional first step in the treatment of HIT. Drugs that inhibit thrombin directly may be necessary in some cases.