The Anatomy of Human Platelets
History
The identification of platelets as a class of blood corpuscules was described by Bizzozzero (1882), the importance of platelets for the formation of a hemostatic plug was first reported by Eberth and Schimmelbusch (1888). Another milestone in platelet research was placed by Aschoff (1925), who’s opinion still provides two keys to the understanding of thrombogenesis:
1.) ‘…aggregations of platelets as they are present in a thrombus can only be sedimented as long as the blood is flowing.’
2.) ‘…formation of fibrin is not a primary event in thrombosis, but is preceded by important changes of the corpuscular elements of the blood. To understand the mechanism of thrombosis it is the latter changes that have to be understood.’
Description
Platelets are the smallest corpuscular components of human blood (diameter 2-4µm) – the physiological number varies from 150.000 to 300.000/mm³ blood. Despite their appearance on the face of it platelets are no cells, as they are not provided with a nucleus. The origin of platelets is the bone marrow, where megakaryocytes – as the results of mitotic proliferation of a committed progenitor cell – liberate platelets as the end product of protrusions of their membrane and cytoplasm. The typical shape of resting platelets is discoid, upon activation they undergo a shape change to a globular form with pseudopodia (up to 5µm long).
Typical smooth discoid shape of resting platelets
Typical spiny spheric shape of activated platelets
Membrane and Receptors
The cover consists of a typical phospholipid bilayer membrane. Embedded in this liquid structure are different kinds of glycoproteins (GP) – the receptors for activation and interaction with other cells. GPIb/IX mediates platelet adhesion to subendothelial collagen (COL) via vonWillebrand factor (vWf), GPIa mediates platelet adhesion via binding to COL. GPIIb/IIIa serves as the binding site for adhesive molecules, which possess a Arg-Gly-Asp-X =RGDX peptide sequence, e.g. fibrinogen, vWf, fibronectin and vitronectin. GPIIb/IIIa therefore permits the intercellular interaction between platelets or between platelets and tumor cells. For the majority of GP-complexes connections to the cytoskeleton have been identified.
Platelet cytoskeleton and Microtubular System (MTS)
Actin (10-20%) and myosin (15-20%) as the major platelet proteins form a three-dimensional network through the cytoplasm of platelets. A second two-dimensional network of shorter actin fibres serves as a membrane skeleton, responsible for the discoid shape of the resting platelet, since membrane receptors are linked via an actin-binding protein (ABP) to this network. Furthermore a marginal bundle of microtubules (MTS) supports the actin membrane skeleton in keeping this discoid shape.
Membrane Systems
In the periphery, close to the MTS a membrane system is located named dense tubular system (DTS), named according to the inherent electron opacity. The DTS serves as a pool for intraplatelet calcium and is the major compartment of arachidonate accumulation and thromboxane synthesis, since it is the site, where the enzyme cyclooxygenase (COX) is localized. The proximity to the MTS suggests its origin as a smooth endoplasmatic reticulum, analog to the sarcoplasmatic reticulum in muscular tissue. Surrounding the organelle zone is a membrane system with invaginations of the platelet’s plasma membrane. Since this system is connected to the platelet’s surface, it is called the open canalicular system (OCS) and offers additional membrane capacity during activation, when the surface-to-volume ratio increases through its extroversion.
Organelles
Organelles are almost evenly distributed in the cytoplasma of resting platelets. Mitochondria serve as energy source, since resting platelets cover their energy expenditure by oxidative phosphorylation, similar to other cells. The most organelles by far are storage granules (~40/platelet). Alpha-granules contain fibrinogen, thrombospondin, F V, von Willebrand factor, beta-thromboglobuline (ß-TG), platelet factor 4 (PF4), etc. Dense bodies contain calcium, serotonin, adenine nucleotides, etc. Following activation platelets release their granula contents, contributing to diverse interactions with other platelets or other cells.
