Platelets or thrombocytes are the smallest figured elements of the blood, with a discoid shape and a diameter between 2 and 3 µm. Unlike white blood cells (or leukocytes) and red blood cells (or erythrocytes), platelets are not real cells, but fragments of the cytoplasm of megakaryocytes located in the red marrow. These, in turn, derive from precursors called megakaryoblasts and appear as large multinucleated cells (diameter from 20 to 15 nm), which after various stages of maturation undergo cytoplasmic fragmentation phenomena, originating from 2000 to 4000 platelets. Thrombocytes, consequently, lack a nucleus (like red blood cells) and structures such as the endoplasmic reticulum and the Golgi apparatus; however, they are delimited by a membrane, which makes each platelet independent from the others, and have granules, various cytoplasmic organelles and RNA.
As anticipated, the dimensions of the plates are particularly small; despite this, their internal structure is extremely complex, since they intervene in a biological process of primary importance called hemostasis (haimablood + stasis block). In synergy with coagulation enzymes, platelets allow the passage of blood from the fluid to the solid state, forming a kind of plug (or thrombus) that obstructs the damaged points of the vessels.
The structure of platelets is extremely complex, such that they are activated only in response to precise and well-determined stimuli; if this were not the case, platelet aggregation in circumstances that are not strictly necessary, or its failure at the moment of need, would have very serious consequences for the organism (pathological thrombogenesis and hemorrhages).
Since incorrect blood clotting plays a role of primary importance in the genesis of strokes and heart attacks, the biological mechanisms that control it are still the subject of numerous studies.
Platelets are always present in the circulation, but are activated only when damage occurs to the walls of the circulatory system.
The structure of platelets, as well as their shape and volume, change profoundly in relation to the degree and stage of activity. In the inactive form, platelets are made up of a paler part (hyalomere) and a more refractile central part (chromomere), rich in granules containing coagulation proteins and cytokines. The cell membrane is rich in protein molecules and glycoproteins, which act as receptors regulating the interaction of the platelet with the surrounding environment (adhesion and aggregation).
Coagulation and platelets
Platelets are just some of the numerous players involved in the clotting process. Following the injury of a blood vessel, the release of certain chemical substances by the endothelial cells, and the exposure of the collagen of the damaged wall, determine the activation of the platelets (the endothelium is a particular tissue lining the internal surface of blood vessels, which under normal conditions separates the collagen matrix fibers from the blood, preventing platelet adhesion).
Platelets rapidly adhere to the exposed collagen in the damaged wall (platelet adhesion) and become activated by releasing particular substances (called cytokines) in the area of the injury. These factors promote the activation and association of other platelets, which aggregate to form a fragile plug, the so-called white thrombus; furthermore, they contribute to strengthening the local vasoconstriction previously triggered by some paracrine substances, released by the damaged endothelium with the aim of decreasing blood flow and pressure. Both reactions are mediated by the release of substances contained within some platelet granules, such as serotonin, calcium, ADP and platelet-activating factor (PAF). The latter triggers a signaling pathway that converts the phospholipids of the platelet membrane into thromboxane A2, which has a vasoconstrictor action and promotes platelet aggregation.
Platelets are extremely fragile: a few seconds after injury to a vessel they aggregate and break, releasing the contents of their granules into the surrounding blood and favoring the formation of a clot.
The aggregation of thrombocytes must obviously be limited to prevent the platelet plug from extending into areas not affected by endothelial damage; platelet adhesion to healthy vessel walls is thus limited by the release of NO and prostacyclin (an eicosanoid).
The primary platelet plug is consolidated in the next phase, in which a series of reactions rapidly follow collectively known as the coagulation cascade; at the end of this event the platelet plug is reinforced by a tangle of protein fibers (fibrin) and is called a clot (the red color of which is due to the incorporation of red blood cells or RBCs). Fibrin originates from a precursor substance, fibrinogen, thanks to the activity of the thrombin enzyme (the final result of two different pathways that participate in the aforementioned cascade).
If on the one hand the prostacyclin released by healthy endothelial cells inhibits platelet adhesion, on the other our body synthesizes anticoagulants – such as heparin, antithrombin III and protein C – to block and regulate some reactions involved in the coagulation cascade, which must necessarily be confined to the injured area.
|PHASES OF THE HEMOSTASIS PROCESS|
|Vascular phase → reduction of the vascular lumen
Contraction of the vascular muscles
Platelet phase → formation of the platelet plug
Coagulation phase → fibrin clot formation:
Cascade of enzymatic reactions
Fibrinolytic phase → clot dissolution:
Activation of the fibrinolytic system
Platelets have an essential role in stopping bleeding, but do not directly intervene in the repair of the damaged vessel, which is instead due to cellular growth and division processes (fibroblasts and vascular smooth muscle cells). Once the leak has been repaired, the clot slowly dissolves and retracts due to the action of the plasmin enzyme trapped inside the clot.