Dynamic Model of Platelet Activation in HIT

The initial event in HIT is the binding of HIT-IgG to PF4-H complexes on the platelet surface. HIT-IgG binds to platelets even if the Fc receptors are blocked (Newman and Chong, 2000). Platelet activation by HIT-IgG is a dynamic process: initially, tiny amounts of PF4-H complexes form on the platelet surface. HIT-IgG binds to these complexes then engaging and cross-linking FcyRIIa by their Fc moiety. FcyRIIa ligation triggers platelet activation and degranulation (including release of the crucial potentiator, ADP). The released PF4 binds heparin and forms more complexes containing antigen on the platelet surface. Thus, positive feedback accelerates platelet activation. HIT-IgG also causes the release of TF and interleu-kin-8 (IL-8) from monocytes (Arepally and Mayer, 2001). In addition, antibodies to IL-8 (a chemokine structurally related to PF4) have been reported in some HIT patients. It appears that these antibodies can activate platelets (Regnault et al., 2003).

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