Platelets play a critical role in hemostasis by forming the primary plug that initially seals vascular defects and by providing a surface that binds and concentrates activated coagulation factors. Platelets are disc-shaped anucleate cell fragments that are shed from megakaryocytes in the bone marrow into the bloodstream. Their function depends on several glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules. α-Granules have the adhesion molecule P-selectin on their membranes (Chapter 3) and contain proteins involved in coagulation, such as fibrinogen, coagulation factor V, and vWF, as well as protein factors that may be involved in wound healing, such as fibronectin, platelet factor 4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β. Dense (or δ) granules contain adenosine diphosphate (ADP) and adenosine triphosphate, ionized calcium, serotonin, and epinephrine.
After a traumatic vascular injury, platelets encounter constituents of the subendothelial connective tissue, such as vWF and collagen. On contact with these proteins, platelets undergo a sequence of reactions that culminate in the formation of a platelet plug (
Fig. 4.5B • Platelet adhesion is mediated largely via interactions with vWF, which acts as a bridge between the platelet surface receptor glycoprotein Ib (GpIb) and exposed collagen (
Fig. 4.6 ). Notably, genetic deficiencies of vWF (von Willebrand disease, Chapter 14) or GpIb (Bernard-Soulier syndrome) result in bleeding disorders, attesting to the importance of these factors.
Fig. 4.6 Plateletadhesionandaggregation.VWFfunctionsasanadhesionbridgebetweensubendothelialcollagenandtheglycoproteinIb(GpIb)plate-letreceptor.PlateletaggregationisaccomplishedbyfibrinogenbindingtoplateletGpIIb-IIIareceptorsondifferentplatelets.Congenitaldeficienciesinthevariousreceptorsorbridgingmoleculesleadtothediseasesindicatedinthecoloredboxes.ADP, Adenosinediphosphate.Deficiency:Bernard-SouliersyndromeEndothelium GpIIb-IIIa complex Fibrinogen von Willebrand factor Deficiency: von Willebrand disease ADP induces conformational change GpIb GpIb Platelet Deficiency: Glanzmann thrombasthenia Subendothelium
Platelets rapidly change shape following adhesion, being converted from smooth discs to spiky “sea urchins” with greatly increased surface area. This change is accompanied by alterations in glycoprotein IIb/IIIa that increase its affinity for fibrinogen (see later), and by the translocation of negatively charged phospholipids (particularly phosphatidylserine) to the platelet surface. These phospholipids bind calcium and serve as nucleation sites for the assembly of coagulation factor complexes.