[Molecular mechanisms and indicators of thrombogenesis after heart valve replacement]

Complex interactions among constituents of blood, components of the subendothelial extracellular matrix, and artificial surfaces of cardiovascular devices are involved in the thrombogenesis following heart valve replacement. Recently, the molecular basis of some of these interactions has been studied in detail. These insights have extended our understanding of interactive processes between platelet receptors, adhesive macromolecules, and abnormal flow conditions during platelet adhesion and aggregation. On the basis of new experimental data, it is concluded that circulating nonactivated platelets are capable of recognizing surface-bound fibrinogen via their glycoprotein receptor GPIIb-IIIa and become activated as a consequence of this specific interaction. In addition, a molecular mechanism has been proposed indicating that high-shear stress created by prosthetic heart valves can induce platelet aggregation. For this platelet reaction, multimeric von Willebrand factor is essential; its structure function relationship and its interaction with the platelet membrane GPIb receptor have been elucidated. The progress made provides specific targets for selective antithrombotic strategies. Moreover, new molecular activation markers have become available which permit appropriate control of established and experimental antithrombotic regimens. This paper reviews some aspects of recent advances in this area.