Platelet

From Wikipedia, the free encyclopedia

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. Dysfunction or low levels of platelets predisposes to bleeding, while high levels, although usually asymptomatic, may increase the risk of thrombosis. An abnormality or disease of the platelets is called a thrombocytopathy.

Histology

Like red blood cells, platelets in mammals are anuclear (no cell nucleus) and discoid (disc shaped); they measure 1.5–3.0 μm in diameter. The body has a very limited reserve of platelets, so they can be rapidly depleted. They contain RNA, mitochondria, a canalicular system, and several different types of granules; lysosomes (containing acid hydrolases), dense bodies (containing ADP, ATP, serotonin, histamine, 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.

Function

Functions of Platelets can be generalised into a number of categories:
  • Adhesion
  • Aggregation
  • Clot retraction
  • Pro-coagulation
  • Cytokine signalling
  • Phagocytosis

    • 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.g. glass), or several other activating factors. 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.

    Adhesion and aggregation

    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 abundant 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).Platelet aggregation is stimulated by 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 .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 of blood (150-400 x 109/L). 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; 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.

    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
    • 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

    • 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 AnatomieSchultze 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..

    Next Page


    This article is based on an article from Wikipedia, the free encyclopedia and is available under the terms of GNU Free Documentation License.
    In the Wikipedia there is a list with all authors of this article available.