A previous blog post concerned the protein tissue factor and how rupture of blood vessel walls initiates fibrin clot formation. Platelets are cell fragments in the blood that normally lead a solitary existence, but they can quickly attach to damaged blood vessels and start participating in blood clot formation. Adherence of platelets at sites of blood vessel rupture usually initiates changes in platelet behavior that allow platelets to fully participate in hemostasis. In particular, activated platelets help support fibrin clot formation and they release chemical signals that stimulate vascular smooth muscle contraction. These two responses to blood vessel wall damage limit blood loss.
Normally, platelets exist in a special environment within the blood. However, extracellular matrix proteins such as collagen are always nearby, just on the other side of the endothelial lining that normally forms the inner surface of blood vessels. Platelets have receptors for extracellular matrix components such as collagen (1). The images (to the right) show platelets that have attached to a solid substrate that had been coated with collagen.
Along with collagen, von Willebrand factor plays an important role in the adhesion of platelets to ruptured blood vessels (2). The binding of platelet receptor proteins to collagen and von Willebrand factor activates signal transduction pathways that change the behavior of platelets, initiating the process of “platelet activation”. Thrombin production is stimulated by blood vessel wall damage (see this earlier discussion), and thrombin also acts on platelets to promote their activation.
Platelet activation involves several important changes in platelet function that contribute to hemostasis:
1. Activated platelets have increased activity of the enzyme cyclooxygenase and produce the signaling molecule thromboxane A2 (3). Thromboxane A2 has two major effects on hemostasis. It both helps to further activate platelets (4) and it acts on vascular smooth muscle to promote vasoconstriction (5), which limits blood flow through damaged blood vessels .
4. Activated platelets aggregate (7, 8) by means of their receptors for von Willebrand factor and fibrinogen. In the context of hemostasis, platelet aggregation occurs in parallel with fibrin clot formation.
The parallel production of thrombin and activated platelets involves several positive feedback processes that result in rapid production of a platelet-rich fibrin clot at locations of blood vessel rupture.
Image credits. These images of platelets adhering to a collagen-coated surface are from Figure 3 in Efficient Inhibition of Collagen-Induced Platelet Activation and Adhesion by LAIR-2, a Soluble Ig-Like Receptor Family Member, © copyright 2010 Lenting et al., an open-access article distributed under the terms of the Creative Commons Attribution License.