ADP is an important autocrine stimulator of platelet activation by HIT-IgG (Chong et al., 1981). This observation was confirmed by Anderson and Anderson (1990) who showed that in vitro FcgRIIa-mediated platelet activation was augmented by ADP. Although ADP potentiates platelet activation by many agonists, Polgar and coworkers (1998) found that pretreatment of platelets with a potent ADP receptor antagonist completely blocked the activity of HIT sera. This observation indicates that ADP and a functional ADP receptor are crucial to FcgRIIa activation by HIT-IgG. However, it should be pointed out that patients receiving ADP receptor antagonists (e.g., clopidogrel) can still develop HIT and HIT-associated thrombosis (Selleng et al., 2005).
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