PLATELETS: CHARACTERISTICS, MORPHOLOGY, ORIGIN, FUNCTIONS - BIOLOGY - 2024

The platelets or thrombocytes are cellular fragments irregular morphology no nucleus and are part of the blood. They are involved in hemostasis - the set of processes and mechanisms that are responsible for controlling bleeding, promoting coagulation.

The cells that give rise to platelets are called megakaryocytes, a process orchestrated by thrombopoietin and other molecules. Each megakaryocyte will progressively fragment and give rise to thousands of platelets.

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Platelets form a kind of "bridge" between hemostasis and the processes of inflammation and immunity. Not only do they participate in aspects related to blood coagulation, but they also release antimicrobial proteins, which is why they are involved in defense against pathogens.

In addition, they secrete a series of protein molecules related to wound healing and connective tissue regeneration.

Historical perspective

The first investigators to describe thrombocytes were Donne et al. Later, in 1872, Hayem's research team corroborated the existence of these blood elements, and confirmed that they were specific to this liquid connective tissue.

Later, with the arrival of electron microscopy in the 1940s, the structure of these elements could be elucidated. The discovery that platelets are formed from megakaryocytes is attributed to Julius Bizzozero - and independently to Homer Wright.

In 1947, Quick and Brinkhous found a relationship between platelets and thrombin formation. After the 1950s, improvements in cell biology and the techniques for studying it led to the exponential growth of existing information on platelets.

Characteristics and morphology

Platelets overview

Platelets are disc-shaped cytoplasmic fragments. They are considered to be small - their dimensions are between 2 to 4 um, with an average diameter of 2.5 um, measured in an isotonic buffer.

Although they lack a nucleus, they are complex elements at the level of their structure. Its metabolism is very active and its half-life is a little over a week.

Platelets in circulation usually exhibit a biconvex morphology. However, when blood preparations treated with a substance that inhibits coagulation are observed, the platelets take a more rounded shape.

Under normal conditions, platelets respond to cellular and humoral stimuli, acquiring an irregular structure and a sticky consistency that allows adherence between their neighbors, forming aggregates.

Platelets can exhibit certain heterogeneity in their characteristics, without this being the product of any disorder or medical pathology. In each microliter of circulating blood, we find more than 300,000 platelets. These help with clotting and preventing potential damage to blood vessels.

Central region

In the central region of the platelet we find several organelles, such as mitochondria, endoplasmic reticulum and Golgi apparatus. Specifically, we find three types of granules inside this blood element: alphas, dense, and lysosomal.

Alpha granules are responsible for housing a series of proteins that are involved in hemostatic functions, including platelet adhesion, blood clotting, and endothelial cell repair, among others. Each plate has 50 to 80 of these granules.

In addition, they contain antimicrobial proteins, since platelets have the ability to interact with microbes, being an important part of the defense against infections. By releasing some molecules, platelets can recruit lymphocytes.

The dense core granules contain mediators of vascular tone, such as serotonin, DNA, and phosphate. They have the capacity for endocytosis. They are less numerous than the alpha ones, and we find two to seven per platelet.

The last type, lysosomal granules, contain hydrolytic enzymes (as occurs in lysosomes that we normally know as organelles of animal cells) that play an important role in dissolving the thrombus.

Peripheral region

The periphery of platelets is called a hyalomer, and it contains a series of microtubules and filaments that regulate the shape and motility of the platelet.

Cellular membrane

The membrane that surrounds platelets has a structure identical to any other biological membrane, composed of a double layer of phospholipids, distributed asymmetrically.

Phospholipids of a neutral nature such as phosphatidylcholine and sphingomyelin are located on the outer side of the membrane, while lipids with anionic or polar charges are located towards the cytoplasmic side.

Phosphatidylinositol, which belongs to the latter group of lipids, participates in the activation of platelets

The membrane also contains esterified cholesterol. This lipid can move freely inside the membrane and contributes to its stability, maintains its fluidity and helps control the passage of substances.

On the membrane we find more than 50 different categories of receptors, among them integrins with collagen-binding capacity. These receptors allow platelets to bind to injured blood vessels.

How do they originate?

Generally speaking, the platelet formation process begins with a stem cell (stem cell) or pluripotential stem cell. This cell gives way to a state called megakaryoblasts. This same process occurs for the formation of the other elements of the blood: erythrocytes and leukocytes.

As the process progresses, the megakaryoblasts originate the promegakaryocyte that will develop into a megakaryocyte. The latter divides and produces a high number of platelets. Below we will develop each of these stages in detail.

The megakaryoblast

The platelet maturation sequence begins with a megakaryoblast. A typical one has a diameter between 10 and 15 um. In this cell, the considerable proportions of nucleus (single, with several nucleoli) in relation to the cytoplasm stand out. The latter is scarce, bluish in color and lacking in granules.

The megakaryoblast resembles a lymphocyte or other cells in the bone marrow, so its identification, based strictly on its morphology, is complicated.

While the cell is in the megakaryoblast state, it can multiply and increase in size. Its dimensions can reach 50 um. In certain cases, these cells can get into circulation, traveling to places outside the marrow where they will continue their maturation process.

The little promegacario

The immediate result of the megakaryoblast is the promegakaryocyte. This cell grows, reaching a diameter close to 80 um. In this state, three types of granules are formed: alpha, dense and lysosomal, dispersed throughout the cell cytoplasm (those described in the previous section).

The basophilic megakaryocyte

In this state, different granulation patterns are visualized and nucleus divisions are completed. The cytoplasmic demarcation lines begin to be seen more clearly, delineating individual cytoplasmic areas, which will later be released in the form of platelets.

In this way, each area contains inside: a cytoskeleton, microtubules and a part of the cytoplasmic organelles. In addition, it has a glycogen deposit that helps platelet support for a period of time greater than a week.

Subsequently, each fragment described develops its own cytoplasmic membrane where a series of glycoprotein receptors are located that will participate in activation, adherence, aggregation and cross-linking events.

The megakaryocyte

The final stage of platelet maturation is called a megakaryocyte. These are cells of considerable size: between 80 and 150 um in diameter.

They are located mainly at the bone marrow level, and to a lesser extent in the lung region and in the spleen. In fact, they are the largest cells we find in the bone marrow.

Megakaryocytes mature and begin to release segments in an event called a platelet burst. When all platelets are released, the remaining nuclei are phagocytosed.

Unlike other cellular elements, the generation of platelets does not require many progenitor cells, since each megakaryocyte will give rise to thousands of platelets.

Process regulation

Colony-stimulating factors (CSF) are generated by macrophages and other stimulated cells participate in the production of megakaryocytes. This differentiation is mediated by interleukins 3, 6, and 11. Megakaryocyte CSF and granulocyte CSF are responsible for synergistically stimulating the generation of progenitor cells.

The number of megakaryocytes regulates the production of megakaryocyte CSFs. That is, if the number of megakaryocytes decreases, the number of CSF megakaryocytes increases.

Incomplete cell division of megakaryocytes

One of the characteristics of megakaryocytes is that their division is not complete, lacking the telophase and leading to the formation of a multilobed nucleus.

The result is a polyploid nucleus (generally 8N to 16N, or in extreme cases 32N), since each lobe is diploid. Furthermore, there is a positive linear relationship between the magnitude of ploidy and the volume of the cell's cytoplasm. The average megakaryocyte with an 8N or 16N nucleus can generate up to 4,000 platelets

Role of thrombopoietin

Thrombopoietin is a 30-70 kD glycoprotein that is produced in the kidney and liver. It is made up of two domains, one for binding to the megakaryocyte CSF and a second which gives it greater stability and allows the molecule to be durable for a longer time limit.

This molecule is responsible for orchestrating the production of platelets. There are numerous synonyms for this molecule in the literature, such as C-mpl ligand, megakaryocyte growth and development factor, or megapoietin.

This molecule binds to the receptor, stimulating the growth of megakaryocytes and the production of platelets. It is also involved in mediating their release.

As the megakaryocyte develops towards platelets, a process that takes between 7 and 10 days, thrombopoietin is degraded by the action of the platelets themselves.

The degradation occurs as a system that is responsible for regulating the production of platelets. In other words, platelets degrade the molecule that stimulates their development.

In which organ are platelets formed?

The organ involved in this formation process is the spleen, which is responsible for regulating the amount of platelets produced. Approximately 30% of the thrombocytes that reside in the peripheral blood of humans are located in the spleen.

Features

Platelets are essential cellular elements in the processes of stopping bleeding and forming the clot. When a vessel is damaged, platelets begin to agglutinate to the subendothelium or the endothelium that suffered the injury. This process involves a change in the structure of the platelets and they release the content of their granules.

In addition to their relationship in coagulation, they are also related to the production of antimicrobial substances (as we noted above), and through the secretion of molecules that attract other elements of the immune system. They also secrete growth factors, which facilitate the healing process.

Normal values ​​in humans

In one liter of blood, normal platelet count should yield a value close to the 150.10 ⁹ until 400.10 ⁹ platelets. This hematological value is usually a little higher in female patients, and as one advances in age (in both sexes, over 65 years) the platelet count begins to decrease.

However, this is not the total or complete number of platelets that the body has, since the spleen is responsible for recruiting a significant number of platelets to be used in an emergency - for example, in the event of an injury or some severe inflammatory process.

Diseases

Thrombocytopenia - low platelet levels

The condition that results in abnormally low platelet counts is called thrombocytopenia. Levels are considered low when the platelet count is less than 100,000 platelets per microliter of blood.

In patients with this pathology, cross-linked platelets, also known as "stress" platelets, are usually found, which are markedly larger.

Causes

The decrease can occur for various reasons. The first one is as a result of taking certain drugs, such as heparin or chemicals used in chemotherapies. The elimination of platelets occurs through the action of antibodies.

Destruction of platelets can also occur as a result of an autoimmune disease, where the body forms antibodies against the platelets in the body itself. In this way, platelets can be phagocytosed and destroyed.

Symptoms

A patient with low platelet levels may have bruises or "bruises" on his body that have appeared in areas that have not received any type of abuse. Along with bruising, the skin may turn pale.

Due to the absence of platelets, bleeding can occur in different regions, often from the nose and gums. Blood can also appear in stool, urine, and when you cough. In some cases, blood can pool under the skin.

The reduction of platelets is not only related to excessive bleeding, it also increases the patient's susceptibility to being infected by bacteria or fungi.

Thrombocythemia - high platelet levels

In contrast to thrombocypenia, the disorder that results in abnormally low platelet counts is termed essential thrombocythemia. It is a rare medical condition, and it usually occurs in males over 50 years of age. In this condition, it is not possible to specify what is the cause of the increase in platelets.

Symptoms

The presence of a high number of platelets results in the formation of harmful clots. The disproportionate increase in platelets causes fatigue, feelings of exhaustion, frequent headaches, and vision problems. Also, the patient tends to develop blood clots and often bleeds.

A major risk of blood clots is the development of an ischemic attack or stroke - if the clot forms in the arteries responsible for supplying the brain.

If the cause that is producing the high number of platelets is known, the patient is said to have thrombocytosis. The platelet count is considered problematic if the numbers exceed 750,000.

Von Willebrand disease

The medical problems associated with platelets are not restricted to abnormalities related to their number, there are also conditions associated with the functioning of platelets.

Von Willebrand's disease is one of the most common clotting problems in humans, and it occurs due to errors in the adhesion of platelets, causing bleeding.

Types of pathology

The origin of the disease is genetic and they have been categorized into various types depending on the mutation that affects the patient.

In type I disease the bleeding is mild and is an autosomal dominant production disorder. It is the most common and is found in almost 80% of patients affected by this condition.

There are also types II and III (and subtypes of each) and the symptoms and severity vary from patient to patient. The variation lies in the clotting factor they affect.

References

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