Platelet Glycoprotein IIbIIIa Inhibitors

Several platelet glycoprotein (GP) IIb/IIIa inhibitors are now available that potently block fibrinogen binding to platelets. They also can reduce thrombin generation by inhibiting the exposure of procoagulant phospholipid surfaces on platelets (Pedicord et al., 1998; Keularts et al., 1998; Hérault et al., 1998). In vitro, GPIIb/IIIa antagonists inhibit platelet aggregation (Hérault et al., 1997), endothelial cell activation (Herbert et al., 1998), and platelet microparticle generation (Mak et al., 1998) by HIT antibodies. However, Fc receptor-dependent platelet activation by HIT antibodies is independent of the GPIIb/IIIa complex (Greinacher et al., 1994a); therefore, GPIIb/IIIa inhibitors do not inhibit platelet granule release (Tsao et al., 1997;

Polgár et al., 1998). As these agents do not have a direct anticoagulant effect, they probably need to be combined with an anticoagulant (danaparoid, lepirudin, or argatroban) to treat HIT. Because there are no data available on the interaction of these newer anticoagulants with the GPIIb/IIIa inhibitors, and because a synergistic effect on bleeding is likely, combined use for the management of HIT should be considered experimental. Theoretically, synthetic GPIIb/IIIa inhibitors with a short half-life could be safer than agents with a long half-life (e.g., abciximab)

Recommendation. GPIIb/IIIa inhibitors should be considered as experimental treatment in HIT and used with caution if combined with anticoagulant drugs (grade 2C).

0 0

Post a comment