revention of blood loss at sites of tissue damage is a complex process requiring adhesion of platelets to the exposed subendothelium, the deposition of further cells onto the monolayer and assembly of a haemostatic plug 1 . Collagen fibres play a critical role in this process through direct and indirect regulation of platelet adhesion and activation. Adhesion of platelets at the high shear forces found within small or damaged arteries and arterioles is mediated through binding of the surface glycoprotein (GP) Ib-IX-V to the adhesion molecule von Willebrand's factor (vWf), which itself attaches to subendothelial collagen fibres. The fast association of vWf to GPIb-IX-V is critical for the rapid platelet arrest that occurs at high shear. In addition, vWf dissociates rapidly from GPIb-IX-V, and interactions with other subendothelial proteins, notably collagen fibres and fibrinogen, are required to hold the platelet at the site of damage. At lower flow rates, collagen and fibrinogen can support adhesion of platelets in the absence of vWf.
As well as supporting adhesion, subendothelial proteins stimulate platelet activation leading to, among other responses, a conformational change in the integrin, GPIIb-IIIa (β£ IIb β€ 3 ), enabling platelet-platelet interactions and the build up of further cells onto the adhered monolayer. Collagen is unique among this group of subendothelial proteins in that it induces platelet activation through the phosphoinositide second messenger pathway. This leads to activation of GPIIb-IIIa, and stimulates release of thromboxanes and other agonists such as ADP that activate further platelets, as well as inducing expression of aminophospholipids, which support key enzymes in the clotting cascade. The importance of collagen in haemostasis is demonstrated by the bleeding problems that occur following impairment of its ability to support adhesion or activation of platelets. Despite this, considerable controversy has surrounded the number and identity of the cell surface receptors that underlie the action of collagen on the platelet.