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Platelets are biconvex discs, fragments of cytoplasm 2–3 µm in diameter, found only in the blood of mammals. Platelets form by budding off from megakaryocytes in the bone marrow, and then entering the circulation.
On a stained blood smear, platelets appear as dark purple spots, about 20% the diameter of red blood cells. The smear is used to examine platelets for size, shape, qualitative number, and clumping.
The primary function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. Hemostasis involves vasoconstriction and converting the blood from a liquid to a gel. The contribution of platelets to gel formation can be summarized as follows: platelets stick to substances outside the interrupted endothelium (adhesion); change shape, turn on receptors and secrete chemical messengers (activation); and then stick to each other (aggregation). Addition of coagulation factors to this platelet plug via the coagulation cascade produces fibrin, which links to platelets and completes gel formation: the clot.
Any abnormality of platelets is a (thrombocytopathy). Dysfunctional platelets cause thrombasthenia. Low platelet concentration is thrombocytopenia. Elevated platelet concentration is thrombocytosis and is either reactive such as to blood loss, or due to one of the myeloprolerative neoplasms.
Normal platelets can respond to an abnormality on the vessel wall rather than to hemorrhage, resulting in inappropriate platelet adhesion/activation and thrombosis. Examples are: extending the fibrin clot of venous thrombosis; extending a ruptured arterial plaque, causing arterial thrombosis; and responding to arteritis with thrombi. An arterial thrombus may partially obstruct blood flow, causing downstream ischemia; or completely obstruct it, causing downstream infarction.
- 1 Discovery and naming
- 2 Measurement
- 3 Symptoms of platelet disorders
- 4 Kinetics
- 5 Dynamics
- 6 Clot formation in non-mammalian vertebrates
- 7 Role in inflammation
- 8 Disorders of platelets
- 9 Platelet rich plasma in wound healing
- 10 Drugs affecting platelets
- 11 Platelet transfusion
- 12 References
- 13 External links
Discovery and naming
The German anatomist Max Schultze (1825–1874) was the first to describe what he called "spherules", which he noted were much smaller than red blood cells, occasionally clumped, and were sometimes found in collections of fibrin material .
Giulio Bizzozero (1846–1901), building on Schultze's findings, in 1882 used "living circulation" to study the blood of amphibians microscopically in vivo. He named Schultz's spherules (It.) piastrine: little plates, which later became platelets. He observed that platelets clump at the site of blood vessel injury, a process that precedes the formation of a clot. This observation confirmed the role of platelets in coagulation.
The term thrombocyte (clot cell) arose in the early 1900's and is sometimes used as a synonym for platelet; but not generally in the scientific literature, especially since the discovery in non-mammalian vertebrates of nucleated cells that have a hemostatic function and were given the name thrombocyte.
Platelet concentration is measured either manually using a hemacytometer or by placing blood in an automated analyzer, which uses light scattering or electrical impedance to count the platelets. The normal range (95% of population) for platelets is 150,000 to 400,000 per cubic millimeter, (the same as per microliter). or 150 - 400 X 109/L. This normal range varies slightly in different laboratories.
Symptoms of platelet disorders
Spontaneous bleeding can be caused by deficient numbers of platelets, dysfunctional platelets, or very excessive numbers of platelets. The bleeding from skin cuts is prompt and excessive and can be controlled by pressure. Spontaneous bleeding into the skin causes petechiae; into mucous membranes causes bleeding gums, nose bleed, and gastrointestinal bleeding. Intraretinal bleeding and intracranial bleeding can also occur.
Normal platelets responding to abnormal vessel walls can result in venous thrombosis and arterial thrombosis. The symptoms depend on he site of thrombosis.
- Megakaryocyte and platelet production is regulated by thrombopoietin, a hormone produced in the liver and kidneys.
- Each megakaryocyte produces between 5,000 and 10,000 platelets during its lifetime.
- An average of 1011 platelets are produced daily in a healthy adult.
- Reserve platelets are stored in the spleen, and are released when needed by splenic contraction induced by the sympathetic nervous system.
- The lifespan of circulating platelets is 5 to 9 days.
- Old platelets are destroyed by phagocytosis in the spleen and liver.
The separation of platelet dynamics into three stages is useful, but artificial. In fact, each stage is initiated in rapid succession, and all simultaneously continue until completion.
Endothelial cells produce von Willebrand factor (vWF), a cell adhesion ligand, which adheres endothelial cells to collagen in the basement membrane. vWF is secreted constitutively into the bloodstream by the endothelial cells, and is stored in endothelial cell and platelet granules.
When the endothelial layer is injured, collagen and vWF anchor platelets to the subendothilium. Platelet GP-V-IX receptor binds with vWF; and GPVI receptor with collagen. (In vitro, platelets can adhere to any negatively charged surface, such as glass.)
Platelet activating substances (ligands) operate through surface G protein coupled receptors to turn on signaling pathways within the platelet. Families of three G proteins (Gi, Gq, G12) operate together for full activation. Most, but not all effects are mediated via cAMP. Another important ligand for activation is the thrombin receptor.
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. Calcium ions are essential for binding of these coagulation factors.
Non-physiological flow conditions (especially high values of shear stress) caused by arterial stenosis, or artificial devices such mechanical heart valves and blood pumps, can lead to platelet activation.
Intraplatelet calcium concentration increases, stimulating actin and myosin filaments, resulting in platelets becoming more spherical and with pseudopods on their surface. Thus they assume a stellate shape: morphological evidence of the activated platelet.
Platelets contain dense granules, lambda granules and alpha granules. Activated platelets secrete the contents of these granules through their canalicular systems to the exterior. Granule characteristics:
- dense (or delta) granules (containing ADP or ATP, calcium, and serotonin)
- lambda granules – similar to lysosomes and contain several hydrolytic enzymes.
- Alpha granules (containing P-selectin, platelet factor 4, transforming growth factor-β1, platelet-derived growth factor, fibronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation factors V and XIII).
Thromboxane A2 synthesis
Classically it was thought that the only mechanism involved in aggregation was the interaction of platelet receptor integrin alpha(IIb)beta(3) with fibrinogen. It is now clear that at least three mechanisms can initiate aggregation, depending on the speed of blood flow (i.e. shear range).
The blood clot is only a temporary solution to stop bleeding; vessel repair is needed. The aggregated platelets secrete substances that promote the invasion of fibroblasts from surrounding connective tissue into the wound to resorb the clot and form a scar. The fibrin is slowly dissolved by the fibrinolytic enzyme, plasmin, and the platelets are cleared by phagocytosis.
Clot formation in non-mammalian vertebrates
Non-mammalian vertebrates instead of having platelets have thrombocytes which have a nucleus and resemble B lymphocytes in morphology. They aggregate in response to thrombin (but not to ADP, serotonin, nor adrenaline, as platelets do).
Role in inflammation
In addition to being the 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. Platelets also secrete platelet-derived growth factor (PDGF).
Disorders of platelets
Disorders associated with a reduced platelet count:
- Gaucher's disease
- Aplastic anemia
- Fetomaternal alloimmune thrombocytopenia
- Some transfusion reactions
Disorders associated with platelet dysfunction or reduced count:
Disorders associated with an elevated count:
- Thrombocytosis, either reactive, or as an expression of myeloproliferative disease: essential thrombocytosis; may feature dysfunctional platelets
Disorders of platelet adhesion or aggregation:
Disorders of platelet activation:
- ADP Receptor defect
Disorders of platelet granule amount or release
Disorders of platelet metabolism
- Decreased cyclooxygenase activity, induced or congenital
- Storage pool defects, acquired or congenital
Disorders associated with compromised platelet signaling:
Platelet rich plasma in wound healing
Platelets release platelet-derived growth factor (PDGF), a potent chemotactic agent; and TGF beta, which stimulates the deposition of extracellular matrix; fibroblast growth factor, insulin-like growth factor 1, platelet-derived epidermal growth factor, and vascular endothelial growth factor. Local application of these factors in increased concentrations through Platelet-rich plasma (PRP) is used as an adjunct to wound healing.
Drugs affecting platelets
Some drugs used to treat inflammation have the unwanted side effect of suppressing normal platelet function. These are the non-steroidal anti-inflammatory agents (NSAIDS). Aspirin irreversibly disrupts platelet function by inhibiting cyclooxygenase-1 (COX1), and hence normal hemostasis. The resulting platelets are unable to produce new cyclooxygenase because they have no DNA. Normal platelet function will not return until the use of 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 usually returning within 24 hours, and taking ibuprofen before aspirin prevents the irreversible effects of aspirin.
Drugs which suppress platelet function are used to prevent thrombus formation. The oral agents are aspirin, clopidogrel, cilostazol, ticlopidine, ticagrelor and prasugrel. The intravenous agents are abciximab, eptifibatide, and tirofiban.
Platelet transfusion is generally used only to correct unusually low platelet counts (typically below (10–15)×109/L). Transfusion is contraindicated in thrombotic thrombocytopenic purpura (TTP), as it fuels the coagulopathy. In patients undergoing surgery, a level below 50×109/L is associated with abnormal surgical bleeding, and regional anaesthetic procedures such as epidurals are avoided for levels below 80×109/L.
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. Recently the AABB Industry Standards for Blood Banks and Transfusion Services (22.214.171.124) has allowed for use of pathogen reduction technology as an alternative to bacterial screenings in platelets.
Pooled whole-blood platelets, sometimes called “random” platelets, are made primarily by two methods. In the US, a unit of whole blood is placed into a large centrifuge in what is referred to as a “soft spin.” At these settings, the platelets remain suspended in the plasma. The platelet-rich plasma (PRP) is removed from the red cells, then centrifuged at a faster setting to harvest the platelets from the plasma. In other regions of the world, the unit of whole blood is centrifuged using settings that cause the platelets to become suspended in the “buffy coat” layer, which includes the platelets and the white blood cells. The “buffy coat” is isolated in a sterile bag, suspended in a small amount of red blood cells and plasma, then centrifuged again to separate the platelets and plasma from the red and white blood cells. Regardless of the initial method of preparation, multiple donations may be combined into one container using a sterile connection device to manufacture a single product with the desired therapeutic dose.
Apheresis platelets are collected using a mechanical device that 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. Pathogen reduction of platelets using for example, riboflavin and UV light treatments can also be carried out to reduce the infectious load of pathogens contained in donated blood products, thereby reducing the risk of transmission of transfusion transmitted diseases.
Platelets do not need to be cross-matched to ensure immune compatibility between donor and recipient unless they contain a significant amount of red blood cells (RBCs). The presence of RBCs results in a reddish-orange color to the product, and is usually associated with whole-blood platelets. Apheresis methods are more efficient than “soft spin” centrifugation at isolating the specific components of blood needed. An effort is usually made to issue type specific platelets, but this is not as critical as it is with RBCs.
Platelets collected by either method have a very short shelf life, typically five days. This results in frequent problems with short supply, as testing the donations often requires up to a full day. Since there are no effective preservative solutions for platelets, they lose potency quickly and are best when fresh.
Platelets are stored under constant agitation at 20–24 °C (68-75.2 °F). Storage at room temperature provides an environment where any bacteria that are introduced to the blood component during the collection process may proliferate and subsequently cause bacteremia in the patient. Regulations are in place in the United States that require products to be tested for the presence of bacterial contamination before transfusion.
Platelets, either apheresis-derived or random-donor, 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. Such volume-reduced platelets are normally transfused only 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. Volume reduced platelets have a shelf life of only four hours.
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