Megakaryopoiesis

• Megakaryopoiesis/Megakaryocytopoiesis


  Production of megakaryocytes
• Megakaryopoiesis


  1. Differentiation/maturation series that will eventually lead to production of platelets

  2. Dilation/delineation of the Demarcation system (DMS) forming longitudinal bundles of tubules called as proplatelet process

  3. Proplatelet process then pierce through the sinusoid-lining endothelial cells shedding platelets

  
• Megakaryocytes


  • Largest cell in the bone marrow and are POLYPLOID (possess multiple chromosome copies)
  • 30-50 um (Wright's stained bone marrow smear) with multi-lobulated nucleus
  • 2 to 4 megakaryocytes under LPO
  • Clusters with hematopoietic stem cells in vascular niches adjacent to the venous sinusoid endothelial cells
  • Responds to TPO (Thrombopoietin)
  • 1 megakaryocyte can produce platelets

  
• Megakaryocyte differentiation and progenitors

  1. Arise from the COMMON MYELOID PROGENITOR (CML) under influence of the transcription factor GATA-1 (globin transcription factor-1) regulated by its cofactor FOG-1 (Friend of GATA)

  2. BFU-Meg

  3. CFU-Meg

  4. LD-CFU-Meg

  5. Endomitosis (form of mitosis that lacks telophase and cytokinesis)

  6. RUNX1 (transcription factor which mediates switch from mitosis to endomitosis)

  
• Growth factors/cytokines involved in megakaryopoiesis

  • CSF-Meg
  • CSF-GM
  • FLT3-Ligand
  • KIT ligand/Stem cell Factor
  • IL-3
  • IL-6
  • IL-11
  • TPO
• • 1-4 megakaryocytes per 1000 BM cells
  • 1% of nucleated cells in the BM

  
• • Cells mistaken as megakaryoblasts: Plasma cell, Ferrata cell, Osteoclast, tumor cell, RS cell
  • Cells mistaken as Promega, Mega: Osteoblast, multinucleated RBC, tumor cell, multinucleated plasma cell, osteoclast
• Platelets


  • Size: 2-4 um
  • Resting/Inactive shape
  • Active shape
  • Platelet satellitism/satelitosis (phenomenon in which platelets form a rosette around the periphery of neutrophils)
  • Cytoplasm: light blue to purple; very granular
  • MPV: 8 to 10 fL
  • Life span: 7-10 days
  • Normal value: 150-400 x 10^9/L (Men: 122-350 x 10^9/L, Women: 140-379 x 10^9/L)
  • Platelet count represents only 2/3 of the available platelets in the platelet pool (1/3 sequestered in the spleen)
  • Reticulated platelets/stress platelets (larger than normal platelets, appear in compensation to thrombocytopenia)

  
• Platelet ultrastructure


  • Peripheral zone (physical and chemical barrier, composed of cholesterol and phospholipids, glycocalyx)
  • Sol-gel zone (stable gel component, microtubules, microfilaments)
  • Membrane systems (Surface Connected Canalicular System, Dense Tubular system)
  • Organelle zone (alpha-granules, dense granules, mitochondria, peroxisomes)
• Contents of alpha granules


  • Beta-Thromboglobulin
  • PF4
  • Fibrinogen
  • Fibronectin
  • Factor V
  • PDGF
  • TGF-B
  • HMWK
  • Factor VIII:vWF
  • Thrombospondin
  • Protein C inhibitor
  • Alpha-2-antiplasmin
  • C1 esterase inhibitor
  • Plasminogen
  • PAI-1
• Contents of dense granules

  • ATP
  • ADP
  • Calcium
  • Magnesium
  • Serotonin
  • Pyrophosphate