ABSTRACT
Platelet aggregation involves the binding of adhesive proteins (fibrinogen, von Willebrand factor) to the αIIbβ3 integrin, which assumes a high-affinity state for adhesive proteins during platelet activation. The occupied integrin sends signals back into the platelet, and the bound adhesive protein forms the bridges linking platelets together. Anti-integrin therapy is designed to inhibit this process in arterial thrombosis. Abciximab, mouse-human chimeric Fab fragments, blocks platelet aggregation and provides proven clinical benefit in acute situations such as in patients with unstable angina undergoing angioplasty or stenting. Eptifibatide and tirofiban are small molecular mass inhibitors also in current use. In contrast, oral inhibitors of αIIbβ3 have proved disappointing, provoking increased mortality without assuring an adequate blockade of αIIbβ3. The problems of using anti-integrin therapy are discussed in this article as are ways of improving its efficacity. Final thoughts provide ideas for a new generation of inhibitors.
KEYWORDS
Anti-integrin therapy - αIIbβ3 - platelets - arterial thrombosis
