It is formed in the bone marrow by fragmentation of the cytoplasm of mature megakaryocytes. One megakaryocyte produces between 1000 – 3000 platelets. Platelet formation is mediated by thrombopoietin (TPO), a hormone that mostly originates from the liver and kidney.
The number of platelets in the blood varies between 150-350 x109 / L. Platelets participate in maintaining normal hemostasis of keeping the blood in fluid state, but mainly known for the constriction and repair of damaged blood vessels to prevent the loss of blood.
Platelets also participate in pathological processes and associated with thrombosis, bleeding, growth of tumor cells, inflammation, and the formation of atherosclerotic plaque.
This is corroborated by the fact that in the proper control of bleeding, it is sufficient to approximately have over 10 x109 / L of platelets to prevent spontaneous bleeding and over 50 x109 / L to control surgical bleeding, for platelets can also maintain participation in a number of pathophysiological processes.
The main function of platelets is a responsibility in the formation of blood clots during hemostasis. This is the most common and often described role of the blood component, whereas the remaining functions remain less known.
In recent decades, substantial efforts has been made in clarifying other physiological and pathological relevance of platelets. These have resulted to a growing number of researches on platelet function on inflammation, immune responses to oxidative stress, aging neurological and psychiatric diseases, lung diseases, tumor diseases, traumatic damage, allergic diseases, nephrology diseases, and diabetes. Read more about platelet function.
Platelets and Blood Clotting
Platelets circulate passively in the bloodstream through blood vessels lined with endothelium.
An injury to the blood vessel or any presence of endothelial damage (including atherosclerotic plaque rupture) is a stimulant to the platelets, triggering them to adhere at the site of damage, become activated, transform in shape, secrete the contents of their granules, and aggregate by binding to each other, creating a primary hemostatic platelet plug (see steps around platelet activation).
Even though platelets play a central role in primary hemostasis, another role is present during the secondary hemostasis on the provision of a phospholipid for the holding of few key coagulation reactions. Read about hemostasis.
After a vascular injury, the platelets can be activated in two different ways, which may act together or independently from each other.
The first method involves exposure of circulating platelets to the subendothelial collagen after tissue damage, causing platelet adhesion and activation via von Willebrand factor (VWF), which makes the bridge between collagen and platelet receptors like glycoprotein Ib (GPIb) / V / IX.
Additionally, the release of cytoplasmic calcium ions enable the secretion of platelet granules with the help of alpha-granules secreted by P-selectin, which causes the adhesion of monocytes and granulocytes in activated platelets and dense granule release of ADP to platelet receptors via P2Y1 released phospholipase A2 to the phospholipid membrane.
The process allows the release of arachidonic acid by COX-1 which produces TxA2 to promote platelet aggregation. The release of Ca2 + induces a conformational change in the platelet GPIIb / IIIa receptor which allows binding of fibrinogen with platelets.
The second way allows the binding of liberated tissue factor (TF) on plasma factor VII (FVII) (of which only 1-2% are in its active form as FVIIa) forming a complex of TF-FVIIa to activate F VII which is then bonded to the surface of cells expressing TF in the active complex of TF-FVIIa.
The process activates FIX and FX to FXa and FIX. Xa can be activated by plasma FV FXa while remaining attached to the surface of the cell, bearing the TF binds to the complex of the FVA to provide a small amount of thrombin from prothrombin conversion.
The amount of thrombin generated is less than 5% of the total amount of thrombin required in the process of blood coagulation and is not sufficient for the conversion of fibrinogen to fibrin for the formation of the hemostatic clot. However, this small amount of thrombin is sufficient for the activation of platelets and their localization at the site of exposure to TF.
Thrombin binds to the surface of non-activated platelets through at least three receptors: GPIbα, PAR1 and PAR 4 thus causing their activation.
The role of platelets in oxidative stress
Oxidative stress is a condition in which the cellular production of reactive oxygen species (ROS) exceeds the capacity of cellular antioxidant defense system, resulting to same time dysfunction and damage to the cell membrane and the endothelium of blood vessels.
Oxidative stress follows many of vascular diseases and is one of the main reasons for the reduction of NO concentration, for the superoxide radical reacts with NO producing peroxynitrite.
Peroxynitrite is a weaker vasodilator of NO, and also causes the formation of lipid peroxidation chain reactions of free radicals. Lipid peroxidation causes damage to lipids in the cell membrane, and the membrane becomes porous and loses its function.
Therefore, lipid peroxidation causes platelet adhesion and aggregation. The oxidative stress is stimulated by the activation of NF-αB which prompts the emergence of proatherogenic cytokine TNFα, interleukins IL-1 and IL-6, and chemokines that inhibits the formation of NO.
Endothelial cells release angiotensin converting enzyme (ACE), which is an antagonist of NO and which converts angiotensin I to angiotensin II, resulting in vasoconstriction. All these processes favor the progression of atherosclerosis.
The role of platelets in inflammation
The endothelium of healthy blood vessels disables the activation of circulating procoagulant proteins, as well as prevent platelet (thrombocyte) activation and adhesion.
In the absence of any vascular trauma, the blood remains in liquid form due to antithrombotic properties of endothelial cells.
However, in cases of inflammatory conditions and appearance of proinflammatory cytokines (even if there has been no damage to blood vessels), it can lead to the activation of endothelial cells, assuming prothrombotic properties.
Secretion of various antithrombotic molecules such as NO, prostaglandins, and ectonucleotide becomes decreased, and the increased expression of proinflammatory and prothrombotic molecules will be observed.
P-selectins, present on activated endothelium and platelets on the surface, can cause the activation and adhesion of platelets as well as the manifestation of atherosclerotic plaque rupture in the occurrence of acute myocardial infarction (AMI).
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