Megakaryopoiesis is the production of platelets from megakaryocytes in the bone marrow. Thrombopoietin stimulates the production and maturation of megakaryocytes from hematopoietic stem cells. Mature megakaryocytes release platelets into circulation through cytoplasmic extensions. Platelets are anucleate cell fragments that play a key role in hemostasis and clot formation through adhesion, secretion, aggregation and retraction. Their structure includes a peripheral zone containing receptors, a sol-gel zone of cytoskeletal elements, and an organelle zone containing granules that secrete factors involved in coagulation, adhesion and aggregation.
Megakaryopoiesis is the production of platelets from megakaryocytes in the bone marrow. Thrombopoietin stimulates the production and maturation of megakaryocytes from hematopoietic stem cells. Mature megakaryocytes release platelets into circulation through cytoplasmic extensions. Platelets are anucleate cell fragments that play a key role in hemostasis and clot formation through adhesion, secretion, aggregation and retraction. Their structure includes a peripheral zone containing receptors, a sol-gel zone of cytoskeletal elements, and an organelle zone containing granules that secrete factors involved in coagulation, adhesion and aggregation.
Megakaryopoiesis is the production of platelets from megakaryocytes in the bone marrow. Thrombopoietin stimulates the production and maturation of megakaryocytes from hematopoietic stem cells. Mature megakaryocytes release platelets into circulation through cytoplasmic extensions. Platelets are anucleate cell fragments that play a key role in hemostasis and clot formation through adhesion, secretion, aggregation and retraction. Their structure includes a peripheral zone containing receptors, a sol-gel zone of cytoskeletal elements, and an organelle zone containing granules that secrete factors involved in coagulation, adhesion and aggregation.
MEGAKARYOPOIESIS ➢ 70% in circulation and 30% is sequestered by the
spleen which can be released in case of trauma or
➢ Production of platelets bleeding ➢ Reference value: 150 – 400 x 109/L Thrombopoietin (TPO) ➢ MPV: 8 – 10 fl ➢ A glycoprotein hormone that is mainly produced by the liver and the kidney Major Structural Feature of Platelet ➢ Important in the production and identification of platelets 1. Peripheral Zone ➢ Composed of membranes which is rich in platelet Features of Terminal Megakaryocyte Differentiation receptor and is responsible for platelet adhesion (plt. to non plt.) and aggregation (plt. to plt.) Point of MKI MKII MKIII ➢ Originates from plasma membrane of the Difference Megakar Promegakaryocyte Megakaryocyte megakaryocytes yoblast 1. %Precursor 20 25 55 Divisions: 2. Diameter 14 – 18 15 – 40 µm 30 – 50 µm µm a. Glycocalyx 3. Nucleolus Round Indented Multilobed - Composed of glycoprotein including: 4. Nucleoli 2–6 Variable Variable • Factor V – Labile Factor; Proaccelarin 5. Chromatin Homogen Condensed Deeply • Factor VIII – Anti-hemophilic Factor ous Condensed • Factor I – Fibrinogen; Blood Clot 6. N:C Ratio 3:1 1:2 1:4 Formation 7. Mitosis Absent Absent Absent 8. Cytoplasm Basophili Basophilic and Azurophilic and b. Plasma Membrane c Granular Granular - Composed of bilayer phospholipid embedded 9. α-granules Present Present Present with integral for surface receptors 10. d-granules Present Present Present 11. DMS Present Present Present Phospholipid – maintain the fluidity of plasma membrane and maintains the structure DMS – Demarcation System • GPIb – serves as the binding and receptor Cytokine/ Diff. to Diff. to Late Thrombop site for vWF (vonWillebrand Factor) Hormone Progeni Megakaryo Maturati oietin necessary for platelet adhesion tor cyte on TPO + + + 0 • GPIIb-IIIa – calcium dependent membrane IL-1 0 + + + protein complex for fibrinogen receptor IL-3 + + 0 – necessary for platelet aggregation IL-6 0 0 + + KL/SCF/ + 0 0 0 Platelet adhesion is mediated by: MCGF 1) vWF CFU-GEMM + 0 0 0 2) GPIb 3) Collagen MCGF – Mast Cell Growth Factor SCF – Stem Cell Factor Platelet aggregation is mediated by: CFU-GEMM – Colony Stimulating Factor-GEMM 1) Calcium 2) Fibrinogen Megakaryocyte 3) GPIIb-IIIa ➢ 1% 4) vWF ➢ Responsible for the production of matured platelets ➢ 2 – 4,000 platelets released 2. Sol-Gel / Framework of Platelets Cytoskeleton ➢ The only cell line where the cells become bigger as ➢ Lies directly beneath the platelets and is they mature composed of: ➢ Do not undergo mitosis ➢ Do not increase in number as they mature a. Microtubules - Composed of protein tubulin which maintains Platelets the platelet disc shape ➢ Anucleate cells b. Microfilament ➢ 2.5 µm in size - Contains actin and myosin which upon ➢ Disc shape or irregular shape stimulation of the platelets will interact to ➢ Dark purple or blue or lavender in wright stain form actomyosin (thrombosthenin) for clot ➢ 10 days life span retraction Platelet Function Actin - for platelet contraction Participates in a sequence of events that leads to the formation of platelet plug and ultimately to formation 3. Organelle Zone / Centromere of stable fibrin clot at the site of vessel interruption ➢ The part where the secretory products of platelets come from a. Primary hemostasis by adhesion, secretion, and aggregation with the end view of hemostatic plug a. α-granules – lack of this results to Gray Plate b. Blood coagulation by releasing Platelet Factor 3 that Syndrome (GPS) plays a big role in forming fibrin clot • Platelet Factor 4 – anti-heparin or c. Clot retraction by actomyosin heparin neutralization d. Helps in localization of bacteria and other small • -thromboglobulin – fibroblast chemotaxis objects and producing aggregates too large to pass • Platelet-derived Growth Factor - mitosis through capillaries • Fibrinogen/ Factor I – blood clot formation • Factor V – labile factor or proaccelarin Platelet Role on Hemostasis • vonWillebrand Factor – for adhesion • Thrombospondin – for adhesion Platelet Factor Activity • Fibronectin – for adhesion PF1 Accelerate the conversion of PT to thrombin Accelerates the clotting of purified • Protein C – for coagulation PF2 fibrinogen by thrombin • A2-Antiplasmin – for fibrinolysis Phospholipid needed in the intrinsic PF3 coagulation pathway b. Dense-granules PF4 Antiheparin • ADP – for aggregation and activation of platelets PF5 Necessary for normal fibrin formation PF6 Anti-fibrinolysis • ATP – source of energy PF7 Formation of intrinsic thromboplastin • Calcium and Magnesium – bivalent cations for platelet activation 3 Pathways: • Serotonin – vasoconstrictor that binds endothelial cells and platelet membranes • Extrinsic • Intrinsic c. Mitochondria • Common – where intrinsic and extrinsic meet (Factor - For ATP synthesis used for platelet X) metabolism Historical Review d. Lysosomal Granules • Acid Phosphatase 2nd Century A.D Hemophilia was first recognized • Hydrolytic Enzyme Moises Maimonides described 2 male 12th Century A.D siblings who died because of excessive 4. Membranous System bleeding after circumcision ➢ Serves as the canal for secretory products Clinical description of families with hemophilia; the disorder was given the a. Dense Tubular System 1803 name hemophilia which means “love - Derived from smooth endoplasmic reticulum of hemorrhage” by Schoenlein and sequesters calcium for platelet activation process The hemophilia was first described in 1828 - It is also the site of platelet cyclooxygenase thesis published by Hoff and of prostaglandin synthesis 1842 Platelets were described Paul Morawitz theory on blood Cyclooxygenase – an enzyme that catalyzes the conversion of 1905 coagulation was accepted arachidonic acid to prostaglandins Lee and White whole blood 1913 coagulation time was performed Arachidonic Acid – unsaturated fatty acid; precursor of prostaglandins Prothrombin time determination was 1930 introduced by Quick b. Open Canalicular System Other test for evaluating hemostatic - Surface connecting system 1940 mechanism like platelet count bleeding - An invagination of the bone marrow time were introduced - Acts as a canal for the release of granule “Cascade and Waterfall” theory was constituents and cytoplasm to the exterior of 1964 introduced the platelet