Platelets (also known as thrombocytes, from the Greek θρόμβος, thròmbos, “lump” and κύτος, cytos, “cell”) are corpuscular elements of the blood without a nucleus. Platelets derive essentially from the lysis of the cytoplasm of bone marrow cells called megakaryocytes (each megakaryocyte produces about 4000 platelets), are round or oval in shape, with a diameter of about 1–3 μm, and circulate in the blood in a variable number, generally between 150–400 × 109/L, with a half-life of about 5–9 days and elimination mainly by splenic catabolism. Even if they are “terminal” elements, as they have no nucleus, these cellular fragments contain inside them three types of granulations, which represent the prerequisite for their functioning. Briefly, the platelet granules are subdivided into α, δ, and γ granules, as described below.

• Granules α (alpha): Slightly opaque, very numerous, and contain mainly fibrinogen, VWF, factors V and XIII, fibronectin, platelet factor 4 (FP4), β-thromboglobulin (β-TG), thrombospondin, and various growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-β

• δ (delta) granules or “dense” granules: Contain mainly histamine, serotonin, calcium, ADP, and ATP

• γ (gamma) or lysosomal granules: Contain mainly lysosomal hydrolases and peroxisomes

As previously described, platelets play an essential role in physiological hemostasis, representing the main effectors of primary hemostasis. Briefly, the role of these small corpuscular elements is to form a first “plug” (called “platelet plug,” formed by the “weak” association of platelets) or bulwark to the leakage of blood following the loss of integrity of the vessel.

To briefly summarize the cascade of events, following vascular damage, the platelets are exposed to the subendothelium (collagen, proteoglycans, fibronectin, and other glycoproteins), and this causes their activation. The platelet response is implemented through biochemical, structural, and morphological alterations. The response to a stimulus is due to the coordinated intervention of the membrane, gran ules, and cytoskeleton and can be divided into several phases, which may overlap (Fig. 1).

Fig1. Primary hemostasis. (Copyright EDISES 2021. Reproduced with permission)

Phase I: Adhesion (to the Subendothelium)

The adhesion of platelets to the subendothelium occurs mainly by binding to the subendothelial collagen, which is exposed following the loss of integrity of the vascular wall (rupture of the endothelial layer). The binding between platelets and collagen is mediated not only by a receptor located on the platelet membrane, the glycoprotein Ia/IIa (gp Ia/IIa), but also by the bridging function exerted by VWF, which binds with a part of the molecule to the collagen and with another part to a receptor located on the platelet mem brane, the glycoprotein Ib (gp Ib). The binding of the platelet to the subendothelium is also mediated by other platelet membrane receptors, such as the glycoprotein Ic/IIa (gp Ic/ IIa), which binds laminin and fibronectin, and, most likely, by the glycoprotein IV (gp IV), which binds to collagen by means of a bridge-bond with thrombospondin. The activation of these platelet receptors is an essential prerequisite for the subsequent phases of the process, which consist of the change in the structure of the platelet (shape change) and its contextual activation. The binding of these first platelets to collagen (through the Ia/IIa receptor) and to VWF (which in turn acts as a bridge for further binding to collagen) causes a deformation of the three-dimensional structure of the plate lets; this change facilitates further aggregation of the plate lets among themselves and above all stimulates the so-called release reaction.

Phase II: Shape Change

 The change in platelet shape (from roughly circular and/or ovaloid elements to a very irregular, almost starry shape, characterized by pseudopod generation) is sustained by the contraction of the platelet cytoskeleton and is a propaedeutic event to the granule release reaction. Of particular interest is the phenomenon known as the “flip-flop” of phosphatidyl serines, in which FP4 is exposed on the platelet surface and represents the physiological binding site of coagulation fac tors during their activation process (described in detail below).

Phase III: Activation and Secretion of Granules (Release)

The activation of the platelet and the consequent release of internal granules (through the open canalicular system by direct exocytosis) are aimed at releasing the numerous mediators contained within the three different types of granules and at enhancing primary hemostasis. This process can be summarized with the term autocrine activation, a mechanism according to which a cellular element (the platelet) produces mediators (mainly ADP and serotonin) that have the function of activating other identical cellular elements (other platelets), thus amplifying the subsequent phenomenon, platelet aggregation. It is also important to remember that the release of TXA2 by the platelets contributes to further stimulating vasoconstriction and thus limiting the caliber of the vessel and the outflow of blood.

Phase IV: Aggregation (Between Them)

 Following the contraction of the cytoskeleton (shape change), activation, and secretion of granules, platelets express on their membrane surface the glycoprotein IIb/IIIa (gp IIb/ IIIa), which specifically binds fibrinogen. Since two contiguous activated platelets express gp IIb/IIIa at the same time, it is not difficult to understand how they can form bridges between them (gp IIb/IIIa-fibrinogen-gp IIb/IIIa), which, therefore, represents the prerequisite for the phenomenon known as platelet aggregation. Thrombospondin also seems to play a role in this process, increasing the size of the platelet aggregate by forming a bridge (cross-link) between platelets and fibrinogen or by positioning itself directly as a bridge between gp IIb and IIIa of two adjacent platelets. Interestingly, platelet aggregation occurs in two phases. Primary aggregation is promoted by a modest concentration of agonists (ADP, collagen, thrombin, and platelet-activating factor) and is essentially reversible, whereas secondary aggregation is determined by higher concentrations of agonists (ADP and TXA2).

The combination of all the phenomena described above, in the absence of quantitative or qualitative platelet abnormalities, effectively contributes to limiting the leakage of blood from the damaged vessel within a few minutes. The platelet plugs thus formed, however, do not have stability requirements to allow a permanent interruption of blood leakage, especially in vessels with higher blood flow and high pressure. The subsequent stabilization of the hemostatic plug will be guaranteed by the intervention of secondary hemostasis, described in detail in the next paragraph.

Platelet Disorders

Although a detailed description of platelet diseases is beyond the scope of this chapter, it may be useful to recall that, like many other human diseases, they are essentially subdivided into quantitative (decrease in the number of platelets, also known as thrombocytopenia) or qualitative (altered platelet function) diseases, which are in turn subdivided into con genital (or hereditary) and acquired diseases. The principal platelet pathologies are described in Table 1. It should be noted that thrombocytopenia with platelet counts greater than 50 × 10⁹/L is usually asymptomatic, 30 to 50 × 10⁹/L is usually accompanied by mild bleeding symptoms, and 10 to 30 × 10⁹/L is associated with moderate bleeding symptoms, whereas a decrease in platelet counts to values <10  × 10⁹/L frequently results in spontaneous mucosal skin bleeding, generalized purpura, and the risk of severe urinary, gastrointestinal, and central nervous system bleeding.

Table1. Main platelet pathologies

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مواضيع ذات صلة

Fibrinolysis

Secondary Hemostasis

Primary Hemostasis and Vessel Participation

Phenotypic and Functional Properties of Erythroid Progenitor Cells

GRAPHICAL ANALYSIS OF VENTRICULAR PUMPING

The Heart Valves Prevent Backflow of blood during Systole

Excitation-Contraction Coupling— function of calcium ions and the transverse tubules

PHYSIOLOGIC ANATOMY OF CARDIAC MUSCLE

الطحال Spleen

الثايمس Thumus

اللوزتان Tonsils

العقد الليمفاوية