Schematic of the mechanism by which heparin induces outside-in, αIIbβ3-dependent platelet potentiation. Multivalent heparin is proposed to interact with the integrin at or near its ligand-binding site, resulting in microclustering of αIIbβ3 complexes on the platelet surface, transactivation of integrin-associated Src-family kinases (SFK), and subsequent activation of downstream signaling pathways that either potentiate (solution heparin) or induce (immobilized heparin) platelet activation. Fibans, such as abciximab and eptifibatide, might be effective in blocking this antibody-independent form of heparin-induced platelet activation.