Platelets (thrombocytes) are small pieces of cytoplasm released from the cytoplasm of mature Megakaryocyte in bone marrow. Although Megakaryocyte are the least number of hematopoietic cells in bone marrow, accounting for only 0.05% of the total number of bone marrow nucleated cells, the platelets they produce are extremely important for the hemostatic function of the body. Each Megakaryocyte can produce 200-700 platelets.
The platelet count of a normal adult is (150-350) × 109/L. Platelets have the function of maintaining the integrity of blood vessel walls. When the platelet count decreases to 50 × When the blood pressure is below 109/L, minor trauma or only increased blood pressure can cause blood stasis spots on the skin and submucosa, and even large purpura. This is because platelets can settle on the vascular wall at any time to fill the gaps left by endothelial cell detachment, and can fuse into vascular endothelial cells, which may play an important role in maintaining endothelial cell integrity or repairing endothelial cells. When there are too few platelets, these functions are difficult to complete and there is a tendency for bleeding. The platelets in the circulating blood are generally in a “stationary” state. But when blood vessels are damaged, platelets are activated through surface contact and the action of certain coagulation factors. Activated platelets can release a series of substances necessary for the hemostatic process and exercise physiological functions such as adhesion, aggregation, release, and adsorption.
Platelet producing Megakaryocyte are also derived from hematopoietic stem cells in bone marrow. Hematopoietic stem cells first differentiate into megakaryocyte progenitor cells, also known as colony forming unit megakaryocyte (CFU Meg). The chromosomes in the nucleus of the progenitor cell stage are generally 2-3 ploidy. When the progenitor cells are diploid or tetraploid, the cells have the ability to proliferate, so this is the stage when Megakaryocyte lines increase the number of cells. When the megakaryocyte progenitor cells further differentiated into 8-32 ploidy Megakaryocyte, the cytoplasm began to differentiate and the Endomembrane system gradually completed. Finally, a membrane substance separates the cytoplasm of Megakaryocyte into many small areas. When each cell is completely separated, it becomes a platelet. One by one, platelets fall off from Megakaryocyte through the gap between the endothelial cells of the sinus wall of the vein and enter the blood stream.
Having completely different immunological properties. TPO is a glycoprotein mainly produced by the kidneys, with a molecular weight of approximately 80000-90000. When platelets in the bloodstream decrease, the concentration of TPO in the blood increases. The functions of this regulatory factor include: ① enhancing DNA synthesis in progenitor cells and increasing the number of cell polyploids; ② Stimulate Megakaryocyte to synthesize protein; ③ Increase the total number of Megakaryocyte, resulting in increased platelet production. At present, it is believed that the proliferation and differentiation of Megakaryocyte are mainly regulated by two regulatory factors on the two stages of differentiation. These two regulators are megakaryocyte Colony-stimulating factor (Meg CSF) and Thrombopoietin (TPO). Meg CSF is a regulatory factor that mainly acts on the progenitor cell stage, and its role is to regulate the proliferation of megakaryocyte progenitor cells. When the total number of Megakaryocyte in bone marrow decreases, the production of this regulatory factor increases.
After platelets enter the bloodstream, they only have physiological functions for the first two days, but their average lifespan can be 7-14 days. In physiological hemostatic activities, platelets themselves will disintegrate and release all active substances after aggregation; It may also integrate into vascular endothelial cells. In addition to aging and destruction, platelets may also be consumed during their physiological functions. Aging platelets are engulfed in the spleen, liver, and lung tissues.
1. Ultrastructure of platelets
Under normal conditions, platelets appear as slightly convex discs on both sides, with an average diameter of 2-3 μ m. The average volume is 8 μ M3. Platelets are nucleated cells with no specific structure under an optical microscope, but complex ultrastructure can be observed under an electron microscope. At present, the structure of platelets is generally divided into surrounding area, sol gel area, Organelle area and special membrane system area.
The normal platelet surface is smooth, with small concave structures visible, and is an open canalicular system (OCS). The surrounding area of the platelet surface is composed of three parts: the outer layer, the unit membrane, and the submembrane area. The coat is mainly composed of various glycoproteins (GP), such as GP Ia, GP Ib, GP IIa, GP IIb, GP IIIa, GP IV, GP V, GP IX, etc. It forms a variety of adhesion receptors and can connect to TSP, thrombin, collagen, fibrinogen, etc. It is crucial for platelets to participate in coagulation and immune regulation. The unit membrane, also known as the plasma membrane, contains protein particles embedded in the lipid bilayer. The number and distribution of these particles are related to platelet adhesion and coagulation function. The membrane contains Na+- K+- ATPase, which maintains the ion concentration difference inside and outside the membrane. The submembrane zone is located between the lower part of the unit membrane and the outer side of the microtubule. Submembrane area contains submembrane filaments and Actin, which are related to platelet adhesion and aggregation.
Microtubules, microfilaments and submembrane filaments also exist in the sol gel region of platelets. These substances constitute the skeleton and contraction system of platelets, playing an important role in platelet deformation, particle release, stretching, and clot contraction. Microtubules are composed of Tubulin, accounting for 3% of the total platelet protein. Their main function is to maintain the shape of platelets. Microfilaments mainly contain Actin, which is the most abundant protein in platelets and accounts for 15%~20% of total platelet protein. Submembrane filaments are mainly fiber components, which can help Actin-binding protein and Actin crosslink into bundles together. On the premise of the presence of Ca2+, actin cooperates with prothrombin, contractin, binding protein, co actin, myosin, etc. to complete platelet shape change, pseudopodium formation, cell contraction and other actions.
Table 1 Main Platelet Membrane Glycoproteins
The Organelle area is the area where there are many kinds of Organelle in platelets, which has a vital impact on the function of platelets. It is also a research hotspot in modern medicine. The most important components in the Organelle area are various particles, such as α Particles, dense particles（ δ Particles) and Lysosome（ λ Particles, etc., see Table 1 for details. α Granules are the storage sites in platelets that can secrete proteins. There are more than ten in each platelet α Particles. Table 1 lists only the relatively main components, and according to the author’s search, it has been found that α There are over 230 levels of platelet derived factors (PDF) present in the granules. Dense particle ratio α The particles are slightly smaller, with a diameter of 250-300nm, and there are 4-8 dense particles in each platelet. At present, it has been found that 65% of ADP and ATP are stored in dense particles in platelets, and 90% of 5-HT in blood is also stored in dense particles. Therefore, dense particles are crucial for platelet aggregation. The ability to release ADP and 5-HT is also being used clinically to evaluate platelet secretion function. In addition, this region also contains mitochondria and Lysosome, which is also a research hotspot at home and abroad this year. The 2013 Nobel Prize in Physiology and Medicine was awarded to three scientists, James E. Rothman, Randy W. Schekman, and Thomas C. S ü dhof, for discovering the mysteries of intracellular transport mechanisms. There are also many unknown fields in the metabolism of substances and energy in platelets through intracellular bodies and Lysosome.
The special membrane system area includes OCS and dense tubular system (DTS). OCS is a tortuous pipeline system formed by the surface of platelets sinking into the interior of platelets, greatly increasing the surface area of platelets in contact with plasma. At the same time, it is an extracellular channel for various substances to enter platelets and release various particulate contents of platelets. The DTS pipeline is not connected to the outside world and is a place for the synthesis of substances within blood cells.