Variation in human platelet glycoprotein VI content modulates glycoproteinVI-specific prothrombinase activity

Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen that fi gures prominently in signal transduction. An addition to binding to type I and III collagens, GPVI is also bound specifically by collagen-related pept ide and convulxin (CVX), a snake venom protein. We developed a quantitative assay of platelet GPVI in which biotin-conjugated CVX binds selectively to GPVI in separated total platelet proteins by a ligand blot procedure. Usin g this approach, we have documented a 5-fold range in platelet GPVI content among 23 normal healthy subjects. In addition, we have determined that CVX -induced or collagen-related peptide-induced prothrombinase activity is dir ectly proportional to the platelet content of GPVI. A statistically signifi cant correlation was observed at 2 CVX concentrations: 14.7 ng/mL (R-2 = 0. 854 and P < 0.001, n = 11) and 22 ng/mL (R-2 = 0.776 and P < 0.001, n = 12) . In previous studies, we established a similar range of expression of the integrin collagen receptor alpha (2)beta (1) on platelets of normal subject s. Among 15 donors, there is a direct correlation between platelet alpha (2 )beta (1) density and GPVI content (R-2 = 0.475 and P = 0.004). In view of the well-documented association of GPVI with platelet procoagulant activity , this study suggests that the variation in GPVI content is a potential ris k factor that may predispose individuals to hemorrhagic or thromboembolic d isorders.