Platelet

Platelet

Platelets, or thrombocytes, are small cytoplasmic bodies derived from cells. They circulate in the blood of mammals and are involved in hemostasis leading to the formation of blood clots. Like red blood cells, platelets have no nucleus.

If the number of platelets is too low, excessive bleeding can occur, however if the number of platelets is too high, blood clots can form (thrombosis) which block blood vessels, and may cause a stroke and/or a heart attack. An abnormality or disease of the platelets is called a thrombocytopathy [cite book
last = Maton
first = Anthea
authorlink =
coauthors = Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright
title = Human Biology and Health
publisher = Prentice Hall
date = 1993
location = Englewood Cliffs, New Jersey, USA
pages =
url =
doi =
id =
isbn = 0-13-981176-1
] which could be either a low number (thrombocytopenia), a decrease in function (thrombasthenia) or an increase in number (thrombocytosis).

Kinetics

*Platelets are produced in blood cell formation (thrombopoiesis) in bone marrow, by budding off from megakaryocytes.
*The physiological range for platelets is 150-400 x 109 per litre.
*Around 1 x 1011 platelets are produced each day by an average adult.
*The lifespan of circulating platelets is 7-10 days.
*This process is regulated by thrombopoietin, a hormone usually produce by liver and kidney.
*Each megakaryocyte produces between 5,000 and 10,000 platelets.
*Old platelets are destroyed by the spleen and by Kupffer cells in the liver.

Thrombus formation

The function of platelets is the maintenance of haemostasis. Primarily, this is achieved by the formation of thrombi, when damage to the endothelium of blood vessels occur. Conversely, thrombus formation must be inhibited at times when there is no damage to the endothelium.

Activation

The inner surface of blood vessels is lined with a thin layer of endothelial cells, that in normal hemostasis, acts to inhibit platelet activation with the production of endothelial-ADPase, noradrenaline, and PGI2. Endothelial-ADPase clears away ADP, a platelet activator, from platelet surface receptors.

Endothelial cells produce a protein called von Willebrand's factor, a cell adhesion ligand, which helps endothelial cells adhere to collagen in the basement membrane. Under physiological conditions, neither collagen nor vWF pass into the bloodstream.

When endothelial damage occurs, platelets come into contact with exposed collagen and vWF, and the inhibitors the endothelium normally secretes are reduced.

The inner surface of blood vessels is lined with a thin layer of endothelial cells. Under this is a layer of collagen. When the endothelial layer is injured, the collagen is exposed.

When the platelets contact collagen, they are activated. They are also activated by thrombin (primarily through PAR-1), ADP receptors (P2Y1 and P2Y12) expressed on platelets. They can also be activated by a negatively charged surface, such as glass.

Platelet activation further results in the scramblase-mediated transport of negatively charged phospholipids to the platelet surface. These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase and prothrombinase complexes.

Shape Change

Activated platelets change in shape to become more spherical, and pseudopods form on their surface.

Granule Secretion

Platelets contain alpha and dense granules. Activated platelets excrete the contents of these granules into their canalicular systems and into surrounding blood. There are two types of granules:

* dense granules (containing ADP or ATP, calcium and serotonin)
* α-granules (containing platelet factor 4, PDGF, fibronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation factors V and XIII).

Thromboxane A2 Synthesisis

Platelet activation initiates the arachidonic acid pathway to produce TXA2. TXA2 is involved in activating other platelets.

Adhesion and aggregation

Platelets aggregate, or clump together, using fibrinogen of vWF as a connecting agent.

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). Other receptors include GPIb-V-IX complex (vWF) and GPVI (collagen).

Activated platelets will adhere, via glycoprotien (GP) Ia, to the collagen that is exposed by endothelial damage

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.

Platelet aggregation is stimulated by ADP, thromboxane and α2 receptor-activation, but inhibited by other inflammatory products like PGI2 and PGD2.

Other functions

* Clot retraction
* Pro-coagulation
* Cytokine signalling
* Phagocytosis [cite journal | author=Movat H.Z"et al" | title=Platelet Phagocytosis and Aggregation| journal= Journal of Cell Biology| year=1965 | pages=531–543 | volume=27 | doi= 10.1083/jcb.27.3.531 | pmid=4957257]

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 [cite journal | author=Weyrich A.S. "et al" | title=Platelets: signaling cells inside the immune continuum. | journal= [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15324742&query_hl=2&itool=pubmed_DocSum Trends Immunol] | year=2004 | pages=489–495 | volume=25 ] [cite journal | author=Wagner D.D. "et al" | title=Platelets in inflammation and thrombosis. | journal= [http://atvb.ahajournals.org/cgi/content/full/23/12/2131 Thromb Vasc Biol] | year=2003 | pages=2131–2137 | volume=23 ] [cite journal | author=Diacovo T.G. "et al" | title=Platelet-mediated lymphocyte delivery to high endothelial venules. | journal= [http://www.sciencemag.org/cgi/reprint/273/5272/252 Science] | year=1996 | pages=252–255 | volume=273 ] [cite journal | author=Iannacone M. "et al" | title=Platelets mediate cytotoxic T lymphocyte-induced liver damage | journal= [http://www.nature.com/nm/journal/v11/n11/abs/nm1317.html;jsessionid=E8E9E840B80EB21437772949A0C44DE5 Nat Med] | year=2005 | pages=1167–1169 | volume=11 ] .

It also secretes e.g. platelet-derived growth factor (PDGF).

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). [Cite web
url=http://www.labtestsonline.org.uk/understanding/analytes/platelet/test.html
title=Platelet count aka thrombocyte count
publisher=
author=Lab Tests Online UK
accessdate=2008-05-22
date=2004-05-28
] 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. 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).

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.

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. 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. Ibuprofen, another NSAID, does not have such a long duration effect, with platelet function returning in 24 hours [cite web|url=http://www.annals.org/cgi/content/full/142/7/I-54|title=Platelet Function after Taking Ibuprofen for 1 Week|accessdate=2008-08-26] , and taking ibuprofen before aspirin will prevent the irreversible effects of aspirin [cite web|url=http://atvb.ahajournals.org/cgi/content/abstract/3/4/383|title=Ibuprofen protects platelet cyclooxygenase from irreversible inhibition by aspirin|accessdate=2008-08-26] . Uremia (a consequence of renal failure) leads to platelet dysfunction that may be ameliorated by the administration of desmopressin.

Medications

Oral agents, often used to alter/suppress platelet function:
*aspirin
*clopidogrel
*cilostazol
*ticlopidine

Intravenous agents, often used to alter/suppress platelet function:
*abciximab
*eptifibatide
*tirofiban

Diseases

Disorders leading to a reduced platelet count:
*Thrombocytopenia
**Idiopathic thrombocytopenic purpura - also known as immune thrombocytopenic purpura (ITP)
**Thrombotic thrombocytopenic purpura
**Drug-induced thrombocytopenia, e.g. heparin-induced thrombocytopenia (HIT)
*Gaucher's disease
*Aplastic anemia

Alloimmune disorders
*Fetomaternal alloimmune thrombocytopenia
*Some transfusion reactions

Disorders leading to platelet dysfunction or reduced count:
*HELLP syndrome
*Hemolytic-uremic syndrome
*Chemotherapy
*Dengue
*Alpha–Delta platelet storage pool deficiency (αδSPD) is a rare inherited bleeding disorder. [ [http://www.informaworld.com/smpp/content~content=a770733890~db=all~jumptype=rss Alpha-delta platelet storage pool deficiency in three generations - Platelets ] ]

Disorders featuring an elevated count:
*Thrombocytosis, including benign essential thrombocytosis (elevated counts, either reactive or as an expression of myeloproliferative disease); may feature dysfunctional platelets

Disorders of platelet adhesion or aggregation:
*Bernard-Soulier syndrome
*Glanzmann's thrombasthenia
*Scott's syndrome
*von Willebrand disease
*Hermansky-Pudlak Syndrome
*Gray platelet syndrome

Disorders of platelet metabolism
*Decreased cyclooxygenase activity, induced or congenital
*Storage pool defects, acquired or congenital

Disorders that indirectly compromise platelet function:
*Haemophilia

Disorders in which platelets play a key role:
*Atherosclerosis
*Coronary artery disease, CAD and myocardial infarction, MI
*Cerebrovascular disease and Stroke, CVA (cerebrovascular accident)
*Peripheral artery occlusive disease (PAOD)
*Cancer [cite journal | author=McCarty OJT. "et al" | title= Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions | journal= [http://bloodjournal.hematologylibrary.org/cgi/content/abstract/96/5/1789 Blood] | year=2000 | pages=1789–1197 | volume=96 ]

Discovery

BrewerBrewer DB. Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet. "Br J Haematol" 2006;133:251-8. PMID 16643426.] traced the history of the discovery of the platelet. 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"Schultze M. Ein heizbarer Objecttisch und seine Verwendung bei Untersuchungen des Blutes. "Arch Mikrosc Anat" 1865;1:1-42.] . He describes "spherules" much smaller than red blood cells that are occasionally clumped and may participate in collections of fibrous material. 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". 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. This observation confirmed the role of platelets in coagulationBizzozero J. Über einen neuen Forrnbestandteil des Blutes und dessen Rolle bei der Thrombose und Blutgerinnung. "Arch Pathol Anat Phys Klin Med" 1882;90:261-332.] .


=Additional

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. The industry standard is for platelets to be tested for bacteria before transfusion to avoid septic reactions, which can be fatal.

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 mechanical 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.

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.

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. 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 proteins.cite journal |author=Schoenfeld H, Spies C, Jakob C |title=Volume-reduced platelet concentrates |journal=Curr. Hematol. Rep. |volume=5 |issue=1 |pages=82–8 |year=2006 |pmid=16537051 |doi=] Volume reduced platelets have a shelf life of only four hours. [ [http://www.cbbsweb.org/enf/2001/pltwashvol.html CBBS: Washed and volume-reduced Plateletpheresis units ] ]

References

ee also

*Hemostasis
*Plateletpheresis


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