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Human blood smear: platelets. This slide has been stained with MayGrunwald Giemsa, and observed with a 100x objective in oil immersion.
Human blood smear: platelets. This slide has been stained with MayGrunwald Giemsa, and observed with a 100x objective in oil immersion.
A 250 ml bag of newly collected platelets.
A 250 ml bag of newly collected platelets.
Thrombocytes
Thrombocytes

Platelets, or thrombocytes, are the cells circulating in the blood that are involved in the cellular mechanisms of primary hemostasis leading to the formation of blood clots. The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells €”such as nutrients and oxygen—and transports Waste products Hemostasis (or Haemostasis refers to a process whereby bleeding is halted in most animals with a closed Circulatory system. A thrombus, or blood clot, is the final product of the Blood coagulation step in Hemostasis. In strict sense, the term platelet should be reserved for anucleated thrombocytes of mammals. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands Nucleated thrombocytes of nonmammalian vertebrates differ from the mammalian plates not only in having a nucleus and thus resembling B lymphocytes, but also these nucleated thrombocytes do not aggregate in response to ADP, serotonin and adrenaline (they do aggregate with thrombin, of course. Serotonin (ËŒsÉ›rəˈtoÊŠnÉ™n ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Thrombin (activated Factor II ') is a Coagulation protein that has many effects in the coagulation cascade. ) [1]. Dysfunction or low levels of platelets predisposes to bleeding, while high levels, although usually asymptomatic, may increase the risk of thrombosis. Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from Thrombosis is the formation of a blood Clot ( Thrombus) inside a Blood vessel, obstructing the flow of Blood through the Circulatory An abnormality or disease of the platelets is called a thrombocytopathy[2] which could be either a decrease in number ie thrombocytopenia, decrease in function ie thrombasthenia or an increase in number ie thrombocytosis.

Contents

Production and degradation

Platelets are produced in hematopoiesis by budding off from megakaryocytes. Haematopoiesis (from Ancient Greek haima blood poiesis to make (or hematopoiesis in the United States sometimes also haemopoiesis or The megakaryocyte is a Bone marrow cell responsible for the production of blood Platelets necessary for normal blood Clotting Megakaryocytes normally Each megakaryocyte produces between 5,000 and 10,000 platelets.

They circulate for approximately one week, and are then destroyed by the spleen and by Kupffer cells in the liver. The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red Kupffer cells, also known as Browicz-Kupffer cells, are specialized Macrophages located in the Liver that form part of the Reticuloendothelial system The liver is a vital organ in the human body and is present in Vertebrates and some other animals

Function

Functions of Platelets can be generalised into a number of categories:

Activation

Platelets are activated when brought into contact with collagen (which is exposed when the endothelial blood vessel lining is damaged), thrombin (primarily through PAR-1), ADP receptors (P2Y1 and P2Y12) expressed on platelets, a negatively charged surface (e. Clot retraction creates more bulk in the clot making it stronger and more resistant to stress Collagen is the main Protein of Connective tissue in Animals and the most abundant protein in Mammals making up about 50% of the whole-body protein The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the Thrombin (activated Factor II ') is a Coagulation protein that has many effects in the coagulation cascade. Protease-activated receptor s are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine g. glass), or several other activating factors. Once activated, they release a number of different coagulation factors and platelet activating factors. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby These substances are normally stored in one of two cytoplasmic granules, either the dense granules (containing ADP or ATP, calcium and serotonin) or the α-granules (containing platelet factor 4, PDGF, fibronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation factors V and XIII). Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Platelet factor 4 (PF4 is a small Cytokine belonging to the CXC Chemokine family that is also known as chemokine (C-X-C motif ligand 4 (CXCL4. In Molecular biology, Platelet-derived growth factor ( PDGF) is one of the numerous Growth factors or Proteins that regulate cell growth Fibronectin is a high-molecular-weight extracellular matrix Glycoprotein containing about 5% Carbohydrate that binds to membrane spanning Receptor proteins Von Willebrand factor (vWF is a Blood Glycoprotein involved in Hemostasis. Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby Factor V is a Protein of the Coagulation system rarely referred to as proaccelerin or labile factor. Factor XIII or fibrin stabilizing factor is an Enzyme ( of the blood coagulation system that crosslinks Fibrin. Platelet activation further results in the scramblase-mediated transport of negatively charged phospholipids to the platelet surface. Scramblase is a hypothetical Protein thought to be responsible for transportation of Phospholipids between the two monolayers of a Lipid bilayer of These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase and prothrombinase complexes. Phosphatidylserine (abbreviated Ptd-L-Ser or PS is a Phospholipid component usually kept on the inner-leaflet the cytosolic side of cell membranes by an enzyme called Translocase Phosphatidylethanolamine ( cephalin, sometimes abbreviated PE) is a Lipid found in Biological membranes. The tenase complex is formed by the activated forms of the blood Coagulation factors Factor VIII and Factor IX. The prothrombinase complex consists of the serine protease Factor Xa, and the protein cofactor Factor Va The complex assembles on negatively charged phospholipid

Adhesion and aggregation

Platelet aggregation is the clumping of platelets together, using fibrin as the connecting agent. Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood Activated platelets have fibrin receptors on their surfaces. Platelet adhesion is the process of platelets sticking to the damaged inner surface of the vessel wall. Adhesion can occur because collagen in the vessel wall is exposed when the endothelial surface lining the vessel is breached, and activated platelets have collagen receptors on their surfaces. Aggregation and adhesion act together to form the platelet plug. The high concentration of myosin and actin filaments in platelets are stimulated to contract during aggregation, further reinforcing the plug. Myosins are a large family of Motor proteins found in Eukaryotic tissues. Actin is a globular roughly 42-kDa Protein found in all eukaryotic cells (except for Nematode sperm where it may be present at concentrations of

The most abundant platelet aggregation receptor is glycoprotein (GP) IIb/IIIa; this is a calcium-dependent receptor for fibrinogen, fibronectin, vitronectin, thrombospondin and von Willebrand factor (vWF). Not to be confused with Peptidoglycan. Glycoproteins are proteins that contain Oligosaccharide chains ( Glycans) covalently attached Fibronectin is a high-molecular-weight extracellular matrix Glycoprotein containing about 5% Carbohydrate that binds to membrane spanning Receptor proteins Other receptors include GPIb-V-IX complex (vWF) and GPVI (collagen). Collagen is the main Protein of Connective tissue in Animals and the most abundant protein in Mammals making up about 50% of the whole-body protein

Platelet aggregation is stimulated by ADP, thromboxane and α2 receptor-activation, but inhibited by other inflammatory products like PGI2 and PGD2. Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine Thromboxane is a member of the family of Lipids known as Eicosanoids. The α2 receptor is a type of Adrenergic receptor. Effect The α2 receptor has several general functions in common with other α-receptors but also Prostacyclin (or PGI2) is a member of the family of Lipid Molecules known as Eicosanoids. Prostaglandin D2 is a Prostaglandin which binds to the receptor PTGDR.

Cytokine signalling

Besides being the chief cellular effector of hemostasis, platelets are rapidly deployed to sites of injury or infection and potentially modulate inflammatory processes by interacting with leukocytes and by secreting cytokines, chemokines and other inflammatory mediators[4] [5] [6] [7]. Hemostasis (or Haemostasis refers to a process whereby bleeding is halted in most animals with a closed Circulatory system. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Chemokines are a family of small Cytokines, or Proteins secreted by cells Proteins are classified as chemokines according to shared structural characteristics

It also secretes e. g. platelet-derived growth factor (PDGF). In Molecular biology, Platelet-derived growth factor ( PDGF) is one of the numerous Growth factors or Proteins that regulate cell growth

Role in disease

High and low counts

A normal platelet count in a healthy person is between 150,000 and 400,000 per mm³ (microlitre) of blood (150–400 x 109/L). The litre or liter (see spelling differences) is a unit of Volume. [8] 95% of healthy people will have platelet counts in this range. Some will have statistically abnormal platelet counts while having no abnormality, although the likelihood increases if the platelet count is either very low or very high.

Both thrombocytopenia (or thrombopenia) and thrombocytosis may present with coagulation problems. Thrombocytopenia (or -paenia, or thrombopenia in short is the presence of relatively few Platelets in Blood. Thrombocytosis is the presence of high Platelet counts in the Blood, and can be either reactive or primary (also termed essential and caused by a Myeloproliferative Generally, low platelet counts increase bleeding risks (although there are exceptions, e. g. immune heparin-induced thrombocytopenia) and thrombocytosis (high counts) may lead to thrombosis (although this is mainly when the elevated count is due to myeloproliferative disorder). Heparin-induced thrombocytopenia (HIT with or without thrombosis (HITT is Thrombocytopenia (low Platelet counts due to the administration of Heparin Thrombocytosis is the presence of high Platelet counts in the Blood, and can be either reactive or primary (also termed essential and caused by a Myeloproliferative

Low platelet counts are generally not corrected by transfusion unless the patient is bleeding or the count has fallen below 5 x 109/L; it is contraindicated in thrombotic thrombocytopenic purpura (TTP) as it fuels the coagulopathy. In patients having surgery, a level below 50 x 109/L) is associated with abnormal surgical bleeding, and regional anaesthetic procedures such as epidurals are avoided for levels below 80-100. The term epidural is often short for epidural anesthesia, a form of Regional anesthesia involving injection of drugs through a Catheter placed into the

Normal platelet counts are not a guarantee of adequate function. In some states the platelets, while being adequate in number, are dysfunctional. For instance, aspirin irreversibly disrupts platelet function by inhibiting cyclooxygenase-1 (COX1), and hence normal hemostasis; Platelets have no DNA and are unable to produce new cyclooxygenase. Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve Normal platelet function will not return until the aspirin has ceased and enough of the affected platelets have been replaced by new ones, which can take over a week. Similarly, uremia (a consequence of renal failure) leads to platelet dysfunction that may be ameliorated by the administration of desmopressin. Uremia is a term used to loosely describe the illness accompanying kidney failure (also called renal failure Renal failure or kidney Desmopressin (trade names DDAVP, Stimate, Minirin) is a Synthetic replacement for antidiuretic hormone, the Hormone that

Medications

Oral agents, often used to alter/suppress platelet function:

Intravenous agents, often used to alter/suppress platelet function:

Diseases

Disorders leading to a reduced platelet count:

Alloimmune disorders

Disorders leading to platelet dysfunction or reduced count:

Disorders featuring an elevated count:

Disorders of platelet adhesion or aggregation:

Disorders of platelet metabolism

Disorders that indirectly compromise platelet function:

Disorders in which platelets play a key role:

Discovery

Brewer[11] traced the history of the discovery of the platelet. Thrombocytosis is the presence of high Platelet counts in the Blood, and can be either reactive or primary (also termed essential and caused by a Myeloproliferative The myeloproliferative diseases ("MPD"s are a group of diseases of the Bone marrow in which excess cells are produced Bernard-Soulier syndrome (BSS also called hemorrhagiparous thrombocytic dystrophy, is an Autosomal recessive bleeding disorder that causes a deficiency Glanzmann's thrombasthenia is an extremely rare disorder of the Blood, in which the Platelets lack Glycoprotein IIb/IIIa. Scott's Syndrome is a hereditary bleeding disorder caused by a defect in the Scramblase gene Von Willebrand disease (vWD is the most common hereditary Coagulation abnormality described in humans although it can also be acquired as a result of other medical conditions Hermansky-Pudlak syndrome (HPS is a rare Autosomal Recessive disorder which results in oculocutaneous albinism (decreased Pigmentation) bleeding Haemophilia (also spelled as hemophilia Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation Coronary artery disease (CAD (or atherosclerotic Heart disease) is the end result of the accumulation of atheromatous plaques within the walls Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply Cerebrovascular disease is a group of brain dysfunctions related to disease of blood vessels supplying the brain A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Peripheral vascular disease (PVD also known as peripheral artery disease (PAD or peripheral artery occlusive disease (PAOD is a collator for all Diseases Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Although red blood cells had been known since van Leeuwenhoek, it was the German anatomist Max Schultze (1825-1874) who first offered a description of the platelet in his newly founded journal Archiv für mikroscopische Anatomie[12]. Antonie Philips van Leeuwenhoek (October 24 1632 &ndash August 30 1723 was a Dutch tradesman and Scientist from Delft, the Netherlands Max Johann Sigismund Schultze ( March 25, 1825 - January 16, 1874) German microscopic Anatomist, was born at Freiburg He describes "spherules" much smaller than red blood cells that are occasionally clumped and may participate in collections of fibrous material. Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood He recommends further study of the findings.

Giulio Bizzozero (1846-1901), building on Schultze's findings, used "living circulation" to study blood cells of amphibians microscopically in vivo. Giulio Bizzozero (1846-1901 was an Italian doctor and medical researcher In vivo ( Latin: within the living means that which takes place inside an organism. One of his findings was the fact that platelets clump at the site of blood vessel injury, which precedes the formation of a blood clot. A thrombus, or blood clot, is the final product of the Blood coagulation step in Hemostasis. This observation confirmed the role of platelets in coagulation[13]. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby

Additional images

Blood cell lineage

In transfusion medicine

Platelets are either isolated from collected units of whole blood and pooled to make a therapeutic dose or collected by Apheresis, sometimes concurrently with plasma or red blood cells. Whole Blood is the term used in Transfusion medicine for human Blood from a standard Blood donation. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood The industry standard is for platelets to be tested for bacteria before transfusion to avoid septic reactions, which can be fatal. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have

Pooled whole blood platelets, sometimes called "random" platelets, are made by taking a unit of whole blood that has not been cooled and placing it into a large centrifuge in what is referred to as a "soft spin. " This splits the blood into three layers: the plasma, a "buffy coat" layer which includes the platelets, and the red blood cells. These are expressed into different bags for storage. From four to six of these are typically pooled into a single bag for a therapeutic dose, though individual components can also be used.

Apheresis platelets are collected using a device which draws blood from the donor and centrifuges the collected blood to separate out the platelets and other components to be collected. The remaining blood is returned to the donor. The advantage to this method is that a single donation provides at least one therapeutic dose, as opposed to the multiple donations for whole blood platelets. This means that a recipient is not exposed to as many different donors and has less risk of transfusion transmitted disease and other complications. Sometimes a person such as a cancer patient who requires routine transfusions of platelets will receive repeated donations from a specific donor to further minimize the risk. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled

Platelets are not crossmatched unless they contain a significant amount of RBCs, which results in a reddish-orange color to the product. This is usually associated with whole blood platelets, as apheresis methods are more efficient than "soft spin" centrifugation at isolating the specific components of blood. An effort is usually made to issue type specific platelets, but this is not as critical as it is with red blood cells. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood

Platelets collected by either method have a very short shelf life, typically five or seven days depending on the system used. This results in frequent problems with short supply, as testing the donations often uses up a full day of this time. Since there are no effective preservative solutions for platelets, they lose potency quickly and are best when fresh.

Platelets, either apheresis or random donor platelets, can be processed through a volume reduction process. In this process, the platelets are spun in a centrifuge and the excess plasma is removed, leaving 10 to 100 ml of platelet concentrate. A centrifuge is a piece of equipment generally driven by a motor that puts an object in Rotation around a fixed axis, applying a force perpendicular to the axis Volume reduced platelets are normally only transfused to neonatal and pediatric patients when a large volume of plasma could overload the child's small circulatory system. The lower volume of plasma also reduces the chances of an adverse transfusion reaction to plasma protiens. [14] Volume reduced platelets have a shelf life of only four hours. [15]

References

  1. ^ Nature 220, 509 - 510 (02 November 1968); doi:10. 1038/220509a0 ADP is not Involved in Thrombin-induced Aggregation of Thrombocytes of a Non-mammalian Vertebrate FRANK A. BELAMARICH, DAVID SHEPRO & MARJA KIEN Biology Department, Boston University, Massachusetts. [1]
  2. ^ Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1.  
  3. ^ Movat H. Zet al (1965). "Platelet Phagocytosis and Aggregation". Journal of Cell Biology 27: 531-543. doi:10.1083/jcb.27.3.531. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  4. ^ Weyrich A. S. et al (2004). "Platelets: signaling cells inside the immune continuum. ". Trends Immunol 25: 489-495.  
  5. ^ Wagner D. D. et al (2003). "Platelets in inflammation and thrombosis. ". Thromb Vasc Biol 23: 2131-2137.  
  6. ^ Diacovo T. G. et al (1996). "Platelet-mediated lymphocyte delivery to high endothelial venules. ". Science 273: 252-255.  
  7. ^ Iannacone M. et al (2005). "Platelets mediate cytotoxic T lymphocyte-induced liver damage". Nat Med 11: 1167-1169.  
  8. ^ Lab Tests Online UK (2004-05-28). "MMIV" redirects here For the Modest Mouse album see " Baron von Bullshit Rides Again " Events 585 BC - A Solar eclipse occurs as predicted by Greek philosopher and scientist Thales, while Alyattes is battling Platelet count aka thrombocyte count. Retrieved on 2008-05-22. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 334 BC - The Greek army of Alexander the Great defeats Darius III of Persia in the Battle of the Granicus.
  9. ^ Alpha-delta platelet storage pool deficiency in three generations - Platelets
  10. ^ McCarty OJT. et al (2000). "Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions". Blood 96: 1789-1197.  
  11. ^ Brewer DB. Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet. Br J Haematol 2006;133:251-8. PMID 16643426.
  12. ^ Schultze M. Ein heizbarer Objecttisch und seine Verwendung bei Untersuchungen des Blutes. Arch Mikrosc Anat 1865;1:1-42.
  13. ^ Bizzozero J. Ãœber einen neuen Forrnbestandteil des Blutes und dessen Rolle bei der Thrombose und Blutgerinnung. Arch Pathol Anat Phys Klin Med 1882;90:261-332.
  14. ^ Schoenfeld H, Spies C, Jakob C (2006). "Volume-reduced platelet concentrates". Curr. Hematol. Rep. 5 (1): 82–8. PMID 16537051.  
  15. ^ CBBS: Washed and volume-reduced Plateletpheresis units

See also

Hemostasis (or Haemostasis refers to a process whereby bleeding is halted in most animals with a closed Circulatory system. Plateletpheresis (also called thrombapheresis or thrombocytapheresis) is the process of collecting Platelets, the components of blood that are involved

Dictionary

platelet

-noun

  1. (cytology) A small colorless disk-shaped particle found in the blood of mammals, which plays an important role in the formation of blood clots.
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