Biomarkers of vascular disease: GPVI shedding

Along with aggregation/thrombosis, platelets modulate a surfeit of important, additional pathophysiologic processes, including inflammation and coagulation. Thrombotic outcomes are associated with high platelet reactivity and with the advent of targeted platelet therapies, reliable laboratory tools to assess changes in platelet activity are vital for the clinician caring for patients undergoing both acute and chronic treatment for cardiovascular disorders. In the absence of a flow cytometer and/or platelet aggregometer, clinical platelet activity assays rely on secreted or released platelet products to act as biomarkers of platelet activation. The soluble ectodomain of glycoprotein (GP)VI is produced by metalloproteolysis of the platelet-specific collagen receptor, GPVI. Soluble GPVI is found in plasma at relatively low levels in healthy donors, but is elevated in plasma from patients with autoimmune-based platelet dysfunction, and in response to shear- or ligand-activation of platelets in vitro. This perspective examines soluble GPVI as a candidate biomarker, specific for platelet activation that is stable in plasma and can be conveniently measured by routine enzyme-linked immunosorbent assay (ELISA). Preliminary studies indicated the presence of elevated levels of soluble GPVI in plasma from patients at risk of thrombosis.