Blood Platelets -- What Are They?
What is a "platelet?"
Platelet production
Platelet structure
The Normal Platelet are small, disc-shaped cells without a nucleus, normally measuring 1 to 2um in diameter and 0.5 to 1.0 um in thickness with a volume of about 6ul. The mean platelet count in normal children and adults is about 250x109/L, usually ranging from 150 to 400x109/L. Platelets are derived from the cytoplasm of megakaryocytes, primarily located in the bone marrow. Normally, a platelet is released to the bloodstream and circulates for about 10 days before its removal, largely by the spleen. Platelets circulate freely without adhesion to the vessel wall or aggregation with other platelet . If stimulated, platelets become spherical, extend pseudopods, and adhere to vessel walls and to each other. It participates with the blood vessel, coagulation factors, and other platelets in the initiation of hemostasis.The megakaryocyte, parent cell of the platelet , is derived from pluripotential stem cells in the bone marrow. Individual megakaryocytes have been estimated to produce as many as 1000 platelets per cell, and apparently very efficient system facilitated by the absence of nuclei in platelets. IL-6 and IL-11 are thought to increase platelet production by megakaryocytes. There are two possible mechanism whereby platelet achieves the transition from being stationary constituents of megakaryocyte cytoplasm in the bone marrow to circulation cells in the bloodstream. One theory is that megakaryocytes themselves are released from the bone marrow and are carried to the pulmonary capillaries, where they fragment into individual platelet . Another is that the bone marrow endothelium has special properties that encourage formation of pseudopods extending from mature megakaryocytes to bone marrow sinuses and thereby directly release platelets into the blood.
Platelets are composed of three principal components: membrane structures, microtubules, and granules. Platelet membrane, overlying glycocalyx, and submembrane structures mediate responses to platelet stimulation and express specific antigenic characteristics.
The surface glycoproteins variously serve as receptors, facilitate platelet adhesion and contraction, and determine expression of specific platelet antigens and antigens shared with other formed elements.
Platelet canalicular system is created by numerous invaginations of the platelet surface and, interspersed among these structures, a set of narrower channels termed the dense tubular system. The canalicular system provides a direct connection between the interior and the surface of the platelet, providing entrance of plasma ingredients into the platelet as well as exit of its own ingredients in connection with the release reaction.
The dense tubular system , on the other hand, is entirely enclosed and is the major site for storage of Ca2+ and the location of cyclooxygenase, the critical enzyme for conversion of membrane-derived arachidonic acid to unstable endoperoxide precursors of prostaglandins and thromboxanes. The major inner structures of the platelet are the cytoskeleton, the microtubules, and a system of contractile proteins. The cytoskeleton provides a framework to anchor the platelet membrane and allow signal transduction to take place. Furthermore , it is a framework against which the contractile proteins of the platelet can operate to initiate shape change and protrusion of pseudopodia at the onset of spreading.
Actin, actin-binding protein, talin, vinculin, stectrin, a-actinin, and several membrane glycoproteins make up the cytoskeleton. Actin-binding protein binds both actin and GPIb-IX. In resting platelet this maintains the discoid shape of the platelet. With activation and calcium influx , calpain is activated, severing the link of actin-binding protein to GPIb-IX. The microtubules are arranged in the form of an inner ring beneath the surface of the platelet and are distinct from the canalicular and dense tubular systems of the membrane zone. The microtubules provide structural support of the platelet, maintain its discoid shape in the resting state, and influence the character of its contractile functions.
Contractile proteins largely consist of myosin and submembrane actin filaments that are anchored to the surface of the platelet by the Tran membrane glycoprotein a-actinin. On stimulation of the platelet , the cytoplasmic concentration of Ca2+ rises and calmodulin is activated and combines with myosin light-chain kinase; this enzyme phosphorylates myosin, leading to the combination of myosin with actin to form contractile act myosin, which mediates the initial changes in shape of the platelet and , ultimately, retraction of the formed clot. There are three kinds of granules in platelets, a-granule, dense granule and lysosomal granule. ?-granules are characterized by moderate electron density and are variable in size and content. These granules contain substances that are intrinsic to the platelet, including the following: platelet factor 4; ß-thromboglobulin; fibrinogen; vWf; PDGF; fibronectin; thrombospondin; IgG; factors V, VIII, XIII; EGF; TGFb; and TFPI. Since it appears that many of the proteins are absorbed from the plasma and not synthesized by the megakaryocyte, selective retention and concentration of certain proteins explains the myriad diverse proteins found in platelet a-granules and why additional ones are continually being identified. a-granule release appears to be all or nothing.
IN general, platelet aggregation is associated with release but at lease in vitro certain "strong" agonists, i.e., collagen and thrombin, can trigger release without aggregation. P selectin or GMP140 is a component of the a-granule membrane. Release involves the granules nearest the platelet surface being transported to the platelet membrane and fusing with it so that a small portion of the postrelease external platelet membrane is made up of the inner membrane of the a-granule, including GMP140. Dense bodies are granules characterized by high electron density and are fewer in number than a-granules. Thes4e structures serve as a depot for nonmetabolic substances that are extrinsic to the platelet and may be picked up or released as indicated. On their release, these substances are particularly critical to platelet aggregation and include the following: ADP, ATP, serotonin, calcium, potassium, and catecholamines. Lysosomal granules are also present in platelets, perhaps representing the original role of the platelet as a white blood cell. These granules contain at lease seven acid hydrolyses . These enzymes may contribute to the intracellular effects of phagocytosis of may create an uncertain amount of damage extracellularly at the site of platelet release. The contents and functions of the nongranular organelles of the platelet may be summarized as follows: mitochondria contain enzymes for oxidative metabolism and thereby provide a major source of energy through the generation of ATP; and peroxisomes contain catalase, which protects the platelet from oxidative damage in connection with periodically intense metabolic activity. Platelet s also contains occasional ribosomal particles and small amounts of RNA.
Platelet receptors
The glycoprotein Ib-IX(CD42): the primary mediator of platelet adhesion. In the presence of flow (arterial shear stress), adhesion is accomplished by the interaction of the von Willebrand factor(vWF) with subendothelial collagen and platelet GPIb-IX. When the platelet glycoprotein Ib-IX complex interacts with thrombin, at lease a partial internal translocation of the Ib-IX complex occurs, presumably mediated by the cytoskeleton. Therefore, the number of Ib-IX complexes on the platelet surfaces activation-sensitive and may vary considerably. There is no conformational activation of the GPIb-IX complex.
Glycoprotein IIb-IIIa: the primary mediator of platelet aggregation. Activation of the complex by strong agonists results in a poorly understood conformational change resulting in the expression of a fibrinogen binding site. This includes a binding site on GPIIIa for the two Arg-Gly-Asp(RGD) sequences in the fibrinogen a chain as well as a separate dodecapeptide binding site on GPIIb. A single molecule of fibrinogen is bound for each IIb-IIIa "active site." Fibrinogen binding to two contiguous platelets serves to bridge the two platelets, resulting in the essential step in development of platelet aggregates. There are 50,000 to 60,000 GPIIb-IIIa sites per platelet that remain relatively constant. Following activation and aggregation, platelet contractility is mediated by the IIb-IIIa complex. This complex may be linked to the platelet cytoskeleton, perhaps via talin.
Platelet
Chapter: 2
Platelets cirrculate in the blood and are derived from megakaryocytes in the
marrow. Like erythrocytes, they are anucleate. However, unlike erythrocytes,
they contain numerous intracytoplasmic granules and are the source of numerous
proinflammatory mediators. In fact, they are quantitatively the greatest
single source of
vasoactive amines in the body. They also are a rich source of
thromboxane A2. It is their
activation that, in part, initiates the vascular phase of the acute
inflammatory response (see Fig. 2-13 in text). To have them play this role
makes imminently good sense, because they are present in large numbers
throughout the circulation, i.e., some are always in close proximity to an
inciting stimulus.
See Also:
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Platelet activating factor (Chapter 2)
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Platelet adhesion: (Chapter 20a)
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Platelet aggregation: (Chapter 20a)
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platelet-derived growth factor (PDGF) (Chapter 3)
Activation
Chapter: 2
This is a concept that can be applied either to cells or to plasma proteins.
The inflammatory process is potentially dangerous, because it can produce
indiscriminate damage to tissues. To minimize this danger, cells and plasma
proteins that are potentially the source of injury normally exist in a
quiescent, non-active state. Until they are needed, they are harmless. The
inflammatory process is designed to marshal its forces locally, i.e., at the
site of an inciting stimulus, rather than systemically. This is achieved, in
part, through the phenomenon of local activation of inflammatory cells and
plasma proteins that can produce proinflammatory mediators. Thus, for example,
increased vascular permeability allows plasma proteins that are precursors of
inflammatory mediators to leak out into the tissues, where they become
activated locally by proteolytic cleavage. Loss of such localization can lead
to exceptionally dangerous systemic processes, such as disseminated
intravascular coagulation. By the same token, leukocytes are quiescent until
they encounter mediators at a site of inflammation that then prime and/or
activate them for a variety of functions, such as enhanced phagocytic activity
and killing.
Platelet adhesion:
Chapter: 20a
The process by which
platelets adhere to the basement membrane at sites of vascular injury. von
Willebrand factor functions as the glue which sticks the platelet to the
basement membrane
collagen. Platelet adhesion is defective in von Willebrand disease.
Platelet aggregation:
Chapter: 20a
The process by which
platelets stick to each other at the site of vascular injury, forming a
platelet plug. Platelets are activated by agonists (thrombin,
collagen, ADP) which activates
fibrinogen receptors and allow platelets to become cross-linked by
fibrinogen. Strong aggregation responses require platelets to synthesize
thromboxane A2, which requires the enzyme cyclo-oxygenase. Fibrin
degradation products can inhibit platelet aggregation by blocking fibrinogen
receptors. Platelet aggregation is abnormal with the use of certain drugs (e.g.,aspirin,
ibuprofen), and in disseminated intravascular coagulation and renal failure.
platelet-derived growth factor (PDGF)
Chapter: 3
PDFG induces proliferation of fibroblasts, microglia, and smooth muscle. It is
stored in
platelet granules and is released following platelet aggregation. PDGF may
also serve as a chemotactic agent for inflammatory cells.
platelet
Histology
•
a cytoplasmic fragment that occurs in the blood of
vertebrates and is associated with blood clotting. Also, THROMBOCYTE.
%20of%20Slide1.GIF)
Blood Clotting
- Blood clotting is a biological system where a number of circulating proteins and blood cells combine to form a "clot" which plugs a site of injury thereby reducing blood loss and also reducing the risk of infection.
- Platelets.
- Origin:
- megakargocytes from bone marrow, lung, kidney.
- Lifespan:
- approximately 10 days.
- Structure:
- bi-concave disc with surface glycoproteins which attach to VWF, FXIa and FVIIIa. Contain a-granules storing fibrinogen, PDGF, and PF4. Also have dense bodies of Ca++, ADP, histamine, serotonin. Microfilments and microtubules are involved in the shape change of platelets during aggregation.
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- See: Platelet Structure just above.
- These are the first cells to be recruited at a wound site, where they form a mechanical plug. The reactions of platelets that enable them to carry out this function are as follows :-
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(1) Adhesion - At injury sites the endothelium is damaged exposing subendothelial tissue and collagen to which the platelets adhere. Following adhesion platelets go through a series of metabolic changes which initiate the subsequent release reactions, shape changes and aggregation. Following adhesion platelets become more spherical and produce long pseudopods which enhance interaction between platelets.
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- See: Adhesion.
- Note: Von Willebrand factor (VWF), released by endothelial cells, is involved in platelet adhesion and later in platelet aggregation. Some hormones control the release of VWF including adrenaline. Therefore stress and exercise indirectly increase VWF levels. Platelets are also activated by thrombin, ADP, adrenaline, and LPS.
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(2) Secretion - Collagen exposure leads to the secretion of a number of factors from granules within the platelet, including adenosine diphosphate (ADP) (induces aggregation) serotonin ( a vasoconstrictor). Factors released from the platelet membrane include arachadonic acid (AA) which leads to thromboxane A2 production TA2 is a vasoconstrictor and it induces platelet aggregation. Other substances released include :-
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(a) fibrinogen - which will be used to
stabilise the clot.
(b) platelet factor 4 ( anti heparin)
(c) inositol triphosphate (controls Ca release). Ca is used to activate some
of the clotting factors of the cascade system.
- The release of substances by platelets is inhibited by factors such as PGI2 ( a prostaglandin) which is secreted by endothelial cells. Therefore repaired endothelium leads to increased PGI2 levels and hence decreased platelet secretion.
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(3) Aggregation - Platelets swell in size and those touching stick together. As they do so more ADP and TA2 is released which in turn causes more aggregation. The end result is a large "platelet plug"
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(4) Pro coagulant activity - Factors released by platelets are involved in the formation of a clot. A membrane phospholipid (platelet factor 3) is involved along with calcium in the activation of the clotting factor X and in the formation of thrombin.
Platelet count
A platelet count is a diagnostic test that determines the number of platelets in the patient's blood. Platelets, which are also called thrombocytes, are small disk-shaped blood cells produced in the bone marrow and involved in the process of blood clotting. There are normally between 150,000-450,000 platelets in each microliter of blood. Low platelet counts or abnormally shaped platelets are associated with bleeding disorders. High platelet counts sometimes indicate disorders of the bone marrow.
The primary functions of a platelet count are to assist in the diagnosis of bleeding disorders and to monitor patients who are being treated for any disease involving bone marrow failure. Patients who have leukemia, polycythemia vera, or aplastic anemia are given periodic platelet count tests to monitor their health.
Description
Blood collection and storage
Platelet counts use a freshly-collected blood specimen to which a chemical called EDTA has been added to prevent clotting before the test begins. About 5 mL of blood are drawn from a vein in the patient's inner elbow region. Blood drawn from a vein helps to produce a more accurate count than blood drawn from a fingertip. Collection of the sample takes only a few minutes.
After collection, the mean platelet volume of EDTA-blood will increase over time. This increase is caused by a change in the shape of the platelets after removal from the body. The changing volume is relatively stable for a period of one to three hours after collection. This period is the best time to count the sample when using electronic instruments, because the platelets will be within a standard size range.
Platelets can be observed in a direct blood smear for approximate quantity and shape. A direct smear is made by placing a drop of blood onto a microscope slide and spreading it into a thin layer. After staining to make the various blood cells easier to see and distinguish, a laboratory technician views the smear through a light microscope. Accurate assessment of the number of platelets requires other methods of counting. There are three methods used to count platelets; hemacytometer, voltage-pulse counting, and electro-optical counting.
The microscopic method uses a phase contrast microscope to view blood on a hemacytometer slide. A sample of the diluted blood mixture is placed in a hemacytometer, which is an instrument with a grid etched into its surface to guide the counting. For a proper count, the platelets should be evenly distributed in the hemacytometer. Counts made from samples with platelet clumping are considered unreliable. Clumping can be caused by several factors, such as clotting before addition of the anticoagulant and allowing the blood to remain in contact with a capillary blood vessel during collection. Errors in platelet counting are more common when blood is collected from capillaries than from veins.
Electronic counting of platelets is the most common method. There are two types of electronic counting, voltage-pulse and electro-optical counting systems. In both systems, the collected blood is diluted and counted by passing the blood through an electronic counter. The instruments are set to count only particles within the proper size range for platelets. The upper and lower levels of the size range are called size exclusion limits. Any cells or material larger or smaller than the size exclusion limits will not be counted. Any object in the proper size range is counted, however, even if it isn't a platelet. For these instruments to work properly, the sample must not contain other material that might mistakenly be counted as platelets. Electronic counting instruments sometimes produce artificially low platelet counts. If a platelet and another blood cell pass through the counter at the same time, the instrument will not count the larger cell because of the size exclusion limits, which will cause the instrument to accidentally miss the platelet. Clumps of platelets will not be counted because clumps exceed the upper size exclusion limit for platelets. In addition, if the patient has a high white blood cell count, electronic counting may yield an unusually low platelet count because white blood cells may filter out some of the platelets before the sample is counted. On the other hand, if the red blood cells in the sample have burst, their fragments will be falsely counted as platelets.
Because platelet counts are sometimes ordered to diagnose or monitor bleeding disorders, patients with these disorders should be cautioned to watch the puncture site for signs of additional bleeding.
Risks for a platelet count test are minimal in normal individuals. Patients with bleeding disorders, however, may have prolonged bleeding from the puncture wound or the formation of a bruise (hematoma) under the skin where the blood was withdrawn.
The normal range for a platelet count is 150,000-450,000 platelets per microliter of blood.
An abnormally low platelet level (thrombocytopenia) is a condition that may result from increased destruction of platelets, decreased production, or increased usage of platelets. In idiopathic thrombocytopenic purpura (ITP), platelets are destroyed at abnormally high rates. Hypersplenism is characterized by the collection (sequestration) of platelets in the spleen. Disseminated intravascular coagulation (DIC) is a condition in which blood clots occur within blood vessels in a number of tissues. All of these diseases produce reduced platelet counts.
Abnormally high platelet levels (thrombocytosis) may indicate either a benign reaction to an infection, surgery, or certain medications; or a disease like polycythemia vera, in which the bone marrow produces too many platelets too quickly.
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| Resources: |
| BOOKS |
| Henry, John B. Clinical Diagnosis and Management by Laboratory Methods. Philadelphia: W. B. Saunders Company, 1996. |
| Merck Manual of Medical Information, edited by Robert Berkow, et al. Whitehouse Station, NJ: Merck Research Laboratories, 1997. |
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