Platelet
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[[Image:Platelets.jpg|thumb|right|230px| Human blood smear: platelets. This slide has been stained with MayGrunwald Giemsa, and observed with a 100x objective in oil immersion.]]
[[Image:Platelet blood bag.jpg|thumb|A 250 ml bag of newly collected platelets.]]
[[Image:Thrombocytes.png|thumb|Thrombocytes]]
'''Platelets''', or '''thrombocytes''', are the [[Cell (biology)|cell]]s circulating in the [[blood]] that are involved in the cellular mechanisms of primary [[hemostasis]] leading to the formation of [[thrombus|blood clot]]s. In strict sense, the term '''platelet''' should be reserved for anucleated thrombocytes of [[mammal]]s. 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.) <ref>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.
[http://www.nature.com/nature/journal/v220/n5166/abs/220509a0.html]</ref>. Dysfunction or low levels of platelets predisposes to [[hemorrhage|bleeding]], while high levels, although usually asymptomatic, may increase the risk of [[thrombosis]]. An abnormality or disease of the platelets is called a '''thrombocytopathy'''<ref>{{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}}</ref> which could be either a decrease in number ie [[thrombocytopenia]], decrease in function ie '''thrombasthenia''' or an increase in number ie '''thrombocytosis'''.
==Production and degradation==
Platelets are produced in [[hematopoiesis]] by budding off from [[megakaryocytes]]. 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 cell]]s in the [[liver]].
==Function==
Functions of Platelets can be generalised into a number of categories:
* Adhesion
* Aggregation
* [[Clot retraction]]
* Pro-coagulation
* Cytokine signalling
* Phagocytosis<ref>{{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}}</ref>
===Activation===
Platelets are [[#Activators|activated]] when brought into contact with [[collagen]] (which is exposed when the [[endothelium|endothelial]] blood vessel lining is damaged), [[thrombin]] (primarily through [[Protease-activated receptor|PAR]]-1), [[Adenosine diphosphate|ADP]] receptors (P2Y1 and P2Y12) expressed on platelets, a negatively charged surface (e.g. glass), or several other activating factors. Once activated, they release a number of different [[coagulation factor]]s and platelet activating factors. These substances are normally stored in one of two cytoplasmic granules, either the dense granules (containing [[Adenosine diphosphate|ADP]] or [[Adenosine triphosphate|ATP]], [[calcium]] and [[serotonin]]) or the α-granules (containing [[platelet factor 4]], [[PDGF]], [[fibronectin]], B-thromboglobulin, [[vWF]], [[fibrinogen]], and [[coagulation factor]]s [[factor V|V]] and [[factor XIII|XIII]]). 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.
===Adhesion and aggregation=== <!--Platelet aggregation redirects here-->
Platelet aggregation is the clumping of platelets together, using [[fibrin]] as the connecting agent. 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.
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]]).
Platelet aggregation is stimulated by [[adenosine diphosphate|ADP]], [[thromboxane]] and [[α2 receptor]]-activation, but inhibited by other inflammatory products like [[PGI2]] and [[PGD2]].
===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<ref>{{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 }}</ref>
<ref>{{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 }}</ref>
<ref>{{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 }}</ref>
<ref>{{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 }}</ref>.
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 10<sup>9</sup>/[[litre|L]]).<ref>{{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
}}</ref>
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 10<sup>9</sup>/L; it is contraindicated in [[thrombotic thrombocytopenic purpura]] (TTP) as it fuels the coagulopathy. In patients having surgery, a level below 50 x 10<sup>9</sup>/L) is associated with abnormal surgical bleeding, and regional anaesthetic procedures such as [[epidural]]s 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. Similarly, [[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.<ref>[http://www.informaworld.com/smpp/content~content=a770733890~db=all~jumptype=rss Alpha-delta platelet storage pool deficiency in three generations - Platelets<!-- Bot generated title -->]</ref>
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]]
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]] <ref>{{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 }}</ref>
==Discovery==
Brewer<ref name=Brewer>Brewer DB. Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet. ''Br J Haematol'' 2006;133:251-8. PMID 16643426.</ref> traced the history of the discovery of the platelet. Although red blood cells had been known since [[Anton van Leeuwenhoek|van Leeuwenhoek]], it was the German anatomist [[Max Johann Sigismund Schultze|Max Schultze]] (1825-1874) who first offered a description of the platelet in his newly founded journal ''Archiv für mikroscopische Anatomie''<ref name=Schultze>Schultze M. Ein heizbarer Objecttisch und seine Verwendung bei Untersuchungen des Blutes. ''Arch Mikrosc Anat'' 1865;1:1-42.</ref>. He describes "spherules" much smaller than red blood cells that are occasionally clumped and may participate in collections of [[fibrin|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 [[thrombus|blood clot]]. This observation confirmed the role of platelets in [[coagulation]]<ref name=Bizzozero>Bizzozero 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.</ref>.
==Additional images==
<gallery>
Image:Illu blood cell lineage.jpg|Blood cell lineage
</gallery>
==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 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.<ref name="pmid16537051">{{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=}}</ref> Volume reduced platelets have a shelf life of only four hours.<ref>[http://www.cbbsweb.org/enf/2001/pltwashvol.html CBBS: Washed and volume-reduced Plateletpheresis units<!-- Bot generated title -->]</ref>
==References==
{{reflist}}
==See also==
*[[Hemostasis]]
*[[Plateletpheresis]]
{{blood}}
{{Coagulation}}
{{Transfusion_medicine}}
[[Category:Blood products]]
[[Category:Coagulation system]]
[[Category:cell biology]]
[[Category:Transfusion medicine]]
[[Category:Human cells]]
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