This project seeks to understand the physiologic and clinical relevance of inherited differences in expression of two receptors that mediate the in initial phase of platelet adhesion to the blood vessel wall, the glycoprotein (GP) Ib-IX-V complex and the integrin a2b1. The impetus for these studies derivess from 1) our observations that there are significant differences in platelet a2b1 density among normal individuals, that these defferences correlate with inheritance of three alleles of the a2 gene, and that these differences influence platelet adhesion to collagens ex vivo; and 2) the recent findings that a single nucleotide dimorphism (T/C) within the Kozak sequence of the 5' untranslated region of the GPIbb gene influences GPIb-IX-V density, while additional GPIBa gene polymorphisms modulate GPIb-IX-V activity.