HEMA 1 Lecture 4 Platelets PDF

MEGAKARYOCYTOPOIESIS / MEGAKARYOPOIESIS DR. GLEN DAWI SAMSON, MPH, DHLM, RMT, DTA, CHA  MEGAKARYOCYTOPOIESIS Development occurs by endomitosis (i.E., Nuclear splitting without cell division). Stages of megakaryocytic maturation: A. Megakaryoblasts B. Promegakaryocytes C. Granular mega...

MEGAKARYOCYTOPOIESIS / MEGAKARYOPOIESIS DR. GLEN DAWI SAMSON, MPH, DHLM, RMT, DTA, CHA  MEGAKARYOCYTOPOIESIS Development occurs by endomitosis (i.E., Nuclear splitting without cell division). Stages of megakaryocytic maturation: A. Megakaryoblasts B. Promegakaryocytes C. Granular megakaryocytes D. Mature megakaryocytes  MEGAKARYOBLAST Committed myeloid progenitor cell Earliest thrombocyte stage where the nucleus divides without cytoplasmic division Results in the formation of giant cells, with a size range of 20-50 um Round nucleus contains 2-6 nucleoli and fine chromatin. The scant basophilic cytoplasm contains no granules  PROMEGAKARYOCYTE Increases size with a range of 20-80 um Indented or lobulated nucleus contains variable number of nucleoli with coarsening chromatin. Basophilic cytoplasm with granules beginning to appear; cytoplasmic tags present Demarcating membrane system (DMS) begins to form.  MEGAKARYOCYTE Increases in size up to 100 um; largest cell in the body It contains a multilobulated nucleus with very coarse chromatin and variable number of nucleoli. Cytoplasm has many small granules that stain purple with Wright's stain.  THROMBOCYTES 2-4 |nm in size, appearing as pale blue cells with azurophilic granules Mature platelets have no nucleus. PLATELETS STRUCTURE, MAJOR ZONES AND FUNCTION  PLATELET ULTRASTRUCTURE Glycocalyx Microtubule and micro filaments Open canalicular system Dense tubular system Mitochondria Glycogen granules Alpha (α) granules Dense granules  PLATELET ULTRASTRUCTURE Glycocalyx is the outer membrane surface. It is rich in glycoproteins, which serve as membrane receptors. a. Glycoprotein Ib b. Glycoproteins IIb and IIIa c. Glycoprotein Va  PLATELET ULTRASTRUCTURE Microtubule and micro filaments These provide an active means of platelet contraction to squeeze out the contents of the cytoplasmic granules. a. Microtubules b. contractile microfilaments  PLATELET ULTRASTRUCTURE Open canalicular system provides direct communication between intracellular and extracellular compartments.  PLATELET ULTRASTRUCTURE Dense tubular system forms a circle within the microtubule a. arachidonic acid metabolism b. calcium-sequestering pump  PLATELET ULTRASTRUCTURE Mitochondria are responsible for energy production. Glycogen granules provide energy substrate.  PLATELET ULTRASTRUCTURE Alpha (α) granules contain contact-promoting factors a. Platelet fibrinogen b. Platelet-derived growth factor (PDGF) c. von Willebrand’s factor (factor VIII:R) d. β-Thromboglobulin (BTG) e. Platelet factor 4 (heparin-neutralizing) f. Fibronectin  PLATELET ULTRASTRUCTURE Dense (Delta) granules contain nonprotein factors a. Adenosine diphosphate (ADP) b. Adenosine triphosphate (ATP) c. 5-Hydroxytryptamine (5-HT; or serotonin) d. Calcium  PLATELET ZONES Peripheral zone Sol-gel (structural) zone Organelle zone Membrane systems  PLATELET ZONES Peripheral zone LOCATION: Glycocalyx, Cytoplasmic membrane, Open canalicular system, Submembranous area COMPONENTS: Factor V, Vwf, Fibrinogen, GPIb/IX, GPIIb/IIIa Others: Glycolipids, phospholipids, proteins, mucopolysaccharides  PLATELET ZONES Sol-gel (structural) zone LOCATION: Circumferential and throughout the platelet COMPONENTS: Microtubules Microfilaments Intermediate filaments All involved in maintenance of shape and shape change on platelet activation  PLATELET ZONES Organelle zone LOCATION: Internally located COMPONENTS: Granules (alpha (50-80 per platelet), Delta (3-8 per platelet)) Lysosomal granules: Hydrolytic Peroxisomes Mitochondria Glycogen particles  ALPHA GRANULES Factor V & XI: Fibrin formation Fibrinogen: Converted to fibrin, platelet aggregation Protein S: Regulation of fibrin formation via protein C pathway TFPI: Regulation of fibrin formation by inhibiting factor VII/tissue factor complex vWF: Binding of platelets to collagen PAI-1: Inhibitor of fibrinolysis PF4: Heparin neutralizing, chemoattractant ß-Thromboglobulin: Chemoattractant Thrombospondin: Stabilization of platelets  DELTA GRANULES ADP: Platelet agonist—positive feedback to enhance platelet response and Recruitment ATP: Activation of Ca2+ channel, agonist for other cells Calcium: Secondary hemostasis Serotonin: Platelet agonist, vasoconstriction  PLATELET ZONES Membrane systems LOCATION: Surface connected open canalicular system (SCCS, OCS) & Dense tubular system (DTS) COMPONENTS: SCCS: important in storage and secretion DTS: Does not connect to platelet surface  PLATELET CHARACTERISTICS The reference range for healthy individuals is 150-450 X 10^9/L or approximately 7-21 per HPF Life span of 8-12 days Wright's stain, stain gray-blue with purple granules. Giant platelets indicate premature release Immature platelets are found in certain diseases  THROMBOCYTE FUNCTION Dependent on platelet secreted proteins, ATP, ADP, calcium, and platelet factors. Plays a major role in primary hemostasis and activation of the secondary hemostasis THANK YOU!