Platelets (thrombocytes) correc
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Platelets (thrombocytes) correc Presentation Transcript

  • 1. PLATELETS(THROMBOCYTES) Lecture by GK Mbassa
  • 2. Purpose of knowing structure, biochemistry and functions of platelets Understand qualitative platelet abnormalities Gain knowledge on hemostasis for treatment of diseases Know platelets role in tumor metastases, atherosclerosis and inflammation resulting from cytoplasmic fragments of megakaryocytes, e.g. arachidonic acid.
  • 3. Morphology of platelets Heterogenous in blood smears; discoid, spheroid, elongated, flat Granular organelles distributed in cytoplasm. Some organelles in centre (granulomere) Platelet cytoplasm is hyalomere, which is clear Platelet is bounded by thin membrane, smooth or having fine projections
  • 4.  EDTA minimizes platelet clumping Platelets clump to other cells (erythrocytes and neutrophils), called satellitism. Platelet volume in dog, pig, man is 7.6 – 8.3 fl, in cattle, equine, sheep, rat, guinea pig, mouse it is 3.2. – 5.4 fl, while in the cat it is 15.1 fl, Platelet counts vary (1- 10 x 1011/l)
  • 5.  Larger platelets are metabolically and functionally more active than small platelets. Scanning electron microscope show platelets to have discoid or lentiform shape, with smooth surfaces, slightly biconcave surface, has shallow indentations at external openings of the open canalicular system Surface projections represent protractions of platelets granules
  • 6.  Surface features of platelets are similar in most species. Platelets diameter length is 1.3 – 4.7 µm in dog, cat, equines, cow, sheep and goat. Platelet thickness is 0.5 µm Transformed platelets acquire pseudopods or projections, found also in normal blood Surface projections occur very fast when blood is taken out of vessel, vary in number and sizes between species
  • 7. Ultrastructural features ofthe platelet Unit membrane covered with amorphous material (external or exterior coat) Bundles of microtubules in matrix beneath membrane Internal structure comprises of heterogenous granules (alpha-granules) Clycogen particles Dense granules Mitochondria Lysosomes Peroxisomes
  • 8.  Poorly developed Golgi complex Endoplasmic reticulum (rarely) Spongy like channels, called open canalicular system) Open canalicular system communicate with substance of platelet, open to surface at invaginations. Open canalicular system is lined by unit membrane, covered by external coat Another system of platelet channels is the dense tubular system. Dense tubular system occurs under marginal band of microtubules and appears to open to surface, but does not open on the platelet surface.
  • 9.  Platelets of many animals have similar morphology. Platelets have two types of granules, (1) alpha-granules, and (2) dense granules. Dense and alpha granules are homogeneously distributed, but vary in electron density, number and size.
  • 10. Functional organization ofthe plateletPlatelet divided into 4 structural regions (1) Peripheral zone (2) Sol-gel zone (3) Organelle zone (4) Membrane system
  • 11. Peripheral zone Composed of external (exterior) coat, unit membrane, sub-membraneous area Functions, maintain platelet integrity, receive and transmit stimuli triggering platelet responses (adhesions, aggregations) Exterior coat has glycoproteins (glycocalyx) contains mucopolysaccharides and Mg2+ dependent AT Pase, plasma proteins (fibrinogen, IgG, IgM), coagulation factors (vitamin K- dependent factors, factors V and VIII)
  • 12.  Glycoproteins have receptors for platelet activation and aggregation. Seven glycoproteins recognised, including glycoprotein 1b (reaction site for von Willebrand factor, a component of coagulation factor VIII) necessary platelet adhesion to endothelium on injured blood vessel Platelet membrane; maintains platelet integrity, rich in phospholipids. Platelet phospholipids function in blood coagulation (eg
  • 13. Sol-gel zone Represented by matrix of platelet cytoplasm, contains microfilaments and microtubules, which function as cytoskeletal elements. Microfilaments and microtubules maintain discoid platelet shape, form contractile system for shape change, pseudopod formation, internal contractions and granule secretion. Microfilaments also function in clot retraction.
  • 14.  Microfilaments are also associated with thrombosthenin, a contractile protein (has actin-myosin) Microtubule tubulin dissolves at 4oC, when exposed to colchicine or vinca alkaloids, leading to platelet shape irregularities.
  • 15. Microfilaments Lysosome Alpha granuleMicrotubulesGolgi complex Open canalicular External coat system Dense tubular system
  • 16. Organelle zone Composed of all internal platelet components, except microtubules, microfilaments (sol-gel zone) components and membrane system. Main component of organelle zone are platelet granules, that are morphologically and biochemically heterogeneous, azurophilic granules (alpha-granules under electron microscope)
  • 17.  Alpha-granules are membrane bound, oval, round, electron dense, contain platelet factor 4 (antiheparin), congulation factor V, fibrinogen, beta-thromboglobulin (a thrombin-sensitive protein), fibronection, factor VIII- related antigen, and a mitogenic or growth factor. Platelets in von Willebrand disease lack factor VIII related antigen
  • 18.  Electron dense granules, called delta granules, or dense bodies contain non metabolic pool ATP and ADP, Ca2+, mono-amines (serotonin, histamine). Dense granules vary with species. Lysosomal granules contain acid hydrolases; acid phosphatase, β- glucuromidase
  • 19.  Contraction of microtubules forces all internal organelles towards the centre squeezing or without squeezing their contents to the exterior via open canalicular system. Platelet activation triggers secretion of various platelet constituents.
  • 20. Membrane systemMemberane system comprises the Open canalicular system Dense tubular systemOpen canalicular system provides a passage for externalization of platelet secretory products and internalization of substances from plasma into the platelet.Dense tubular system provides a site for sequestration of Ca2+ and localization of enzymes needed for prostaglandin synthesisRelease of Ca2+ from the dense tribular system triggers platelet aggregation
  • 21. Platelet constituentsPlatelet Constituent FunctionlocationExterior coat Fibrinogen Platelet aggregationMembrane Arachidonic acid Prostaglandin synthesis Plaletet factor 3 Enhances (phospholipid) Coagulation cAMP Inhibits release reaction
  • 22. Platelet constituentsMicrotubules Tubulin Cytoskeleton ContractilityMicrofilaments Thrombosthenin Shape change, clot reaction, release reactionAlpha-granules Beta- Impedes thromboglobulin prostacylin production from endothelial cells Catalase Enzymic process
  • 23. Factor VIII- Platelet adhesion torelatedantigen subendotheliumFibrinogen Shape change, clot reaction, release reactionBeta- Impedes prostacylinthromboglobuli production fromn endothelial cellsFibronectin Adherence to extracellular matrix Promote wound healing
  • 24. Vasoconstriction Endothelial damage Anticoagulation ADP Platelet Collagen Plasmin adherence vWF PF3 tp Clot dissolution ADP Thrombin (IIA) PGI2 Anti-aggregation Platelet release Fibrin TS and deposition Clot retraction aggregation Platelet plague Growth factor Endothelial regeneration Extrinsic activation Intrinsic activation
  • 25. STRUCTURAL ABNORMALITIESOF PLATELETS Morphologic changes occur in platelets after Contact with non physiologic surfaces. Exposure to platelet aggregation agents.
  • 26.  The structural abnormalities involving: Sphering Degranulation (ECF) Budding Indentations Pseudopods Vacuolation.
  • 27. PLATELET METABOLISM The dry platelet has 50% proteins, 8.5% carbohydrates, the rest are lipids, and others chemicals. Platelets get energy from Anaerobic glycolysis Hexose monophosphate pathway Oxidative phosphorylation in mitochondria
  • 28.  Arachidonic acid metabolism Arachidonate metabolites function in haemostasis and thrombosis involving platelet-vessel wall interactions and synthesis of prostaglandins and thromboxanes. Stimulated platelets liberate arachidomic acid from membrane phospholipids, by phospholipase and corphospholipase A.
  • 29.  Platelets stimulators Thrombin ADP Collagen Epinephrine Calcium ionophores.
  • 30. FUNCTIONS OF PLATELETS Platelets have been observed to play a role in the following; Maintain haemostasis Maintain vascular integrity (with endothelial cells) Blood coagulation, (provide platelet phospholipid (platelet factor 3), carry coagulation factors on their surfaces. Clot retraction (contractile protein system involving thrombosthenin).
  • 31.  Role in thrombosis and embolism Role in flammatory responses (activation of chemotactic substances release of cationic proteins and vasoactive amines) Phagocytosis of small particles and bacteria Role in atherosclerosis Platelets are secretory cells, producing proteins, procoagulant, anti-heparin, inflammatory and growth-promoting activities
  • 32. QUALITATIVE ANDQUANTITATIVE DISORDERS OFPLATELETS Platelet disorders are characterized as qualitative or functional and qualitative or both. Qualitative platelet disorders include; Hereditary, e.g Glanzmann’s thrombosthenia
  • 33.  Acquired Quantitative platelet disorders include; Thrombocytopaenia is the most frequent, causes hemorrhagic diathesis Thrombocytosis may be physiologic or reactive Thrombosythemia a proliferative disorder of megakaryocytes in bone marrow, associated with severe thrombocytosis
  • 34.  Signs, diagnosis and common abnormalities There are hereditary or acquired qualitative platelets disorders, and vary in severity. They involve multiple functional platelet abnormalities, and caused by;  extrinsic abnormalities defects in morphological and biochemical components of platelets or megakaryocytes
  • 35.  Qualitative and quantitative platelet defects have similar clinical signs despite of differences in origin and may differ in pathogenesis. Signs of qualitative platelet disorders (1)Increased tendency to bleed (2)Prolonged bleeding time, in a situation of increased or normal platelet count. (3)Set on early in life. (4)Familial occurrence
  • 36.  Diagnostic examination of qualitative platelet disorders (1)Platelet count (2)Platelet distribution on blood films (3)Platelet morphology (4)Bleeding time (5)Prothrombin time (6)Partial prothrombin time. (7)In vitro platelet aggregation test (adrenalin, collagen, ADP ristocetin).
  • 37.  (8)Platelet retention test in glass bead column (9)In vivo platelet adhesion test Common abnormalities in platelet function Aggregation Retention in glass bead column Availability of platelet factors 3 (PF-3)
  • 38.  Cause of acquired qualitative platelet functional disorders Acquired platelet disorders occur with or without hemorrhagic manifestations, occur in; Renal disease, with uremia Liver disease Myeloproliferative disorders Lymphoproliferative disorders Macroglobulinemia Plasma cell myeloma
  • 39.  Immune mediated disorders (autoimmune thrombocytopenia, autoimmune hemolytic anemia, systemic lupus erythrematosus, circulating fibrin, circulating fibronogen split products – cirrhosis, disseminated intravascular coagulation) Vitamin deficiency Congenital heart disease Acquired storage pool disease (deficiency of platelet dense bodies) Drug therapy (non-steroid anti- inflammatory drugs eg. asprin
  • 40.  Causes of hereditary qualitative platelet disorders 1. Glanzmann’s thrombasthenia Glanzmann’s thrombasthenia, a hemorrhagic disorder due to autosomal recessive inheritance characterized by; Greatly prolonged bleeding time in presence of normal platelet counts and coagulation factors Spontaneous purpuric mucosal and cultaneous bleeding Early onset in life
  • 41.  The defects include Lack of platelet aggregation with ADP, collagen, thrombin, clot retraction PF-3 availability Absence of membrane glycoprotein IIb, IIIa, Lack of receptors for fibrinogen Short life of platelets (4 days, normal 7 days).
  • 42.  2. Hereditary thrombopathia Hereditary thrombopathia occurs in dogs due to autosomal inheritance, characterized by markedly abnormal platelet function, depressed ADP and collagen aggregation and slightly prolonged bleeding time.
  • 43.  3. Von Willebrand’s disease A hereditary bleeding disorder Prolonged bleeding time, normal clot retraction Quantitative and qualitative disorder of von Willbrand’s factor associated with factor VIII – related antigen (VIII-Ag). Decreased adherence of platelet to injured vessels and glass beeds.