Platelet
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A 250 ml bag of newly collected platelets. |
Platelets or
thrombocytes are the
cell fragments circulating in the
blood that are involved in the cellular mechanisms of primary
haemostasis leading to the formation of
blood clots. Dysfunction or low levels of platelets predisposes to
bleeding, while high levels, although usually asymptomatic, may increase the risk of
thrombosis.
Like
red blood cells, platelets are anuclear (no
cell nucleus) and discoid (
disc shaped); they measure 1.5â€"3.0
μm in diameter. The body has a very limited reserve of platelets, so they can be rapidly depleted. They contain
RNA, a
canalicular system, and several different types of granules;
lysosomes (containing
acid hydrolases), dense bodies (containing
ADP,
ATP serotonin and
calcium) and alpha granules (containing
fibrinogen,
factor V,
vitronectin,
thrombospondin and
von Willebrand factor), the contents of which are released upon activation of the platelet. These granule contents play an important role in both
hemostasis and in the inflammatory response.
Production
Platelets are produced in the
bone marrow; the progenitor cell for platelets is the
megakaryocyte. This large, multinucleated cell sheds platelets into the circulation.
Thrombopoietin (
c-mpl ligand) is a hormone, mainly produced by the
liver, that stimulates platelet production. It is bound to circulating platelets; if platelet levels are adequate, serum levels remain low. If the platelet count is decreased, more thrombopoeitin circulates freely and increases marrow production.
Circulation
The circulating life of a platelet is 9â€"10 days. After this it is sequestered in the
spleen.
Decreased function (or absence) of the spleen may increase platelet counts, while
hypersplenism (overactivity of the spleen, e.g. in
Gaucher's disease,
leukemia and
cirrhosis) may lead to increased elimination and hence low platelet counts.
Function
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, with receptors expressed on
white blood cells or the endothelial cells of the blood vessels, among other activators. Once activated, they release a number of different
coagulation factors and platelet activating factors.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.The platelets adhere to each other via adhesion receptors or
integrins, and to the endothelial cells in the wall of the blood vessel forming a haemostatic plug in conjunction with
fibrin. The high concentration of
myosin and
actin filaments in platelets are stimulated to contract during aggregation, further reinforcing the plug.The most common platelet adhesion 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)
Activators
There are many known platelet activators. They include
*
Collagen, especially with
von Willebrand factor which is exposed when
endothelial blood vessel lining is damaged and binds to
GPVI on the platelet;
*
Thrombin, primarily through cleavage of the extracellular domain of
PAR1 and PAR4;
*
Thromboxane A2 (TxA
2), which binds to TP;
*
ADP through creation of TxA
2, which can be blocked by conversion of ADP to
cAMP;
*
Human neutrophil elastase (HNE) cleaves the α
IIbβ
3 integrin on the platelet surface;
*
P-selectin, which binds to
PSGL-1 on endothelial cells and white blood cells; and
*
Convulxin, (a purified protein from snake venom) which binds to GPVI.
Inhibitors
*
Prostacyclin opposes the actions of Thromboxane A
2*
Nitric oxide *Clotting factors
II,
IX,
X,
XI,
XII*
Nucleotidases by breaking down ADP
Drugs that inhibit platelet function
*
Aspirin inhibits cyclooxygenase-1
*
Clopidogrel inhibits
ADP receptors
*
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis
*
Abciximab blocks fibrinogen receptors
*
β-lactam antibiotics alteration of agonist receptors
*
Quinidine calcium channel blocker
High and low counts
A normal platelet count in a healthy person is between 150,000 and 400,000 per mm
3 of blood. 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
9/
L); it is contraindicated in thrombotic thrombocopenic purpura (TTP) as it fuels the coagulopathy. In patients having surgery, a level below 50 (x 10
9/
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; normal platelet function may not return until the aspirin has ceased and all 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.
Diseases
Disorders leading to a reduced platelet count:
*
Thrombocytopenia**
Idiopathic thrombocytopenic purpura**
Thrombotic thrombocytopenic purpura**Drug-induced thrombocytopenia, e.g.
heparin-induced thrombocytopenia (HIT)
*
Gaucher's disease*
Aplastic anemiaAlloimmune disorders
*
Fetomaternal alloimmune thrombocytopenia*Some transfusion reactions
Disorders leading to platelet dysfunction or reduced count:
*
HELLP syndrome*
Hemolytic-uremic syndrome*
ChemotherapyDisorders 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 diseaseDisorders of platelet metabolism
*Decreased
cyclooxygenase activity, induced or congenital
*Storage pool defects, acquired or congenital
Disorders in which platelets play a pathogenetic role:
*
Hepatitis B Virus infection
Brewer
[Brewer DB. Max Schultze (1865), G. Bizzozero (1882) and the discovery of the platelet. Br J Haematol 2006;133:251-8. DOI 10.1111/j.1365-2141.2006.06036.x.] 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 that 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
coagulation[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.].
*
hemostasis*
plateletpheresis
