Platelet
From Pharmpedia
Platelets or thrombocytes are the blood cell fragments that are involved in the cellular mechanisms that lead to the formation of blood clots. Low levels or dysfunction predisposes for bleeding, while high levels - although usually asymptomatic - may increase the risk of thrombosis.
Contents |
Anatomy
Like red blood cells, platelets are anuclear and discoid; they measure 1.5-3.0 μm in diameter. The body has a very limited reserve of platelets and 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.
Physiology
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 9-10 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 or leukemia) 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-4), ADP, with receptors expressed on white blood cells or the endothelial cells of the blood vessels, amoung other activators. Once activated, they release a number of different coagulation factors and platelet activating factors, they also provide a catalytic phospholipid 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 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 (TxA2) which binds to TP,
- ADP through creation of TxA2, and it can be blocked by conversion of ADP to cAMP,
- Human neutrophil elastase (HNE) cleaves the αIIbβ3 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 A2
- Nitric oxide
- Clotting factors II, IX, X, XI, XII
- Nucleotidases by breaking down ADP
Role in disease
High and low counts
A normal platelet count in a healthy person is between 150 and 400 (x 109/L of blood).
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 thrombocopenic 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.
Note however that the actual platelet count is only part of the story, since they may not all be functioning normally. For example, aspirin irreversibly prevents platelets from working correctly and so normal hemostasis may not return until the aspirin is ceased and the affected platelets have been replaced by new ones, which may take over a week.
Diseases
Disorders leading to a reduced platelet count:
- Thrombocytopenia
- Idiopathic thrombocytopenic purpura
- Thrombotic thrombocytopenic purpura
- Drug-induced thrombocytopenia
- Thrombocytosis, including benign essential thrombocytosis
- Gaucher's disease
Disorders leading to platelet dysfunction or reduced count:
Disorders of platelet adhesion or aggregation:
Disorders of platelet metabolism
- Decreased cyclooxygenase activity, induced or congenital
- Storage pool defects, acquired or congenital
Transfusion
Platelets are separated from donated blood using an apheresis blood separator. This is necessary because platelets will not survive at the low temperatures used to store red blood cells, so they must be stored separately using porous storage bags that allow oxygen to flow in and carbon dioxide to flow out. Typical storage is between 20 and 24 °C and continuously agitated to promote gas exchange. Because of the higher risks of bacterial growth at this temperature, platelets are generally only stored for up to 5 days.
A bag of platelets can be separated from multiple bags of whole blood or from a single donor connected to the separator for less than two hours. By drawing and returning blood repeatedly, a bag of high quality platelets can be prepared in about 90 minutes. Platelets collected from a single donor can reduce the infection rates of blood-transmitted diseases.
People with few platelets or platelets that are dysfunctional may benefit from a platelet transfusion, however patients with autoimmune disorders that affect platelets may not.
See also
| Cardiovascular system - Blood |
| Red blood cells - White blood cells - Platelets - Blood plasma |
| White blood cells |
| Granulocytes (Neutrophil granulocytes, Eosinophil granulocytes, Basophil granulocytes) - Lymphocytes - Monocytes |
| Coagulation |
| Coagulation factors: - Fibrin (I) - (Pro)thrombin (II) - FV - FVII - FVIII - FIX - FX - FXI - FXII - FXIII - HMWK - vWF - Tissue factor |
| Inhibitors: Antithrombin - Protein C - Protein S - Protein Z - ZPI - TFPI |
| Fibrinolysis: Plasmin - tPA/urokinase - PAI-1/2 - α2-AP - TAFI |
| The source of this article is Wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL |
Retrieved from "http://www.pharmpedia.com/Platelet"
This page has been accessed 224 times. This page was last modified 21:28, 3 September 2005. All content, except where otherwise noted, is licensed under a Creative Commons Attribution License.
