Results 1 to 2 of 2

Thread: Basic and Clinical Knowledge about platelet

  1. #1
    PharmD Year 1 TomHsiung's Avatar
    Join Date
    Jan 2013
    Location
    Chengdu, Sichuan, China
    Posts
    593

    Default Basic and Clinical Knowledge about platelet

    Regulation of Platelet Number
    The platelet count is regulated by the relative rates of platelet production and clearance. Kinetic studies have demonstrated that the average platelet life span is 7-10 days. Platelets that are lost through senescence, activation, or other processes are replaced by new platelets derived from bone marrow megakaryocytic. Platelet production from megakaryocytic, in turn, is driven by the hormone thrombopoietin (TPO) and its cellular receptor, c-Mpl.

    Thrombopoietin and the thrombopoietin receptor c-Mpl
    A healthy adult produces 1 x 1011 to 3 x 1011 platelets per day, although production can increase tenfold during times of high demand. The number of circulating platelets is regulated chiefly by TPO, which binds to megakaryocytic and hematopoietic stem cells via c-Mpl.

    c-Mpl is a member of the class I hematopoietic growth factor receptor superfamily and activates several signaling pathways in megakaryocytes, resulting in megakaryocyte proliferation and differentiation, ultimately resulting in platelet production. c-Mpl is also expressed on mature platelets, which bind and clear TPO from the circulation.

    TPO is secreted constitutively from the liver; although its synthesis may increase slightly during thrombocytopenic states, its overall production is relatively constant. As a consequence, the level of free TPO is regulated primarily by the number of circulating platelets, the platelet life span, and the megakaryocyte mass. Recent mouse studies have challenged this paradigm. The Ashwell-Morell receptor on murine hepatocytes binds platelets that have lost silica acid residues on their surface. Binding activates a JAK-STAT signaling pathway, resulting in increased hepatic TPO mRNA and TPO production. The relevance of this pathway to normal human thrombopoiesis is not yet known.

    In conditions such as aplastic anemia, which is characterized by a low platelet count and decreased bone marrow megakaryocyte mass, free TPO levels are high. In immune thrombocytopenia, the megakaryocyte mass may be expanded and platelet clearance is accelerated. This results in enhanced TPO clearance and plasma TPO levels that usually fall within the normal range despite thrombocytopenia. TPO alone, however, does not fully support megakaryocyte polyploidization in vitro, suggesting that additional factors, such as stem cell factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and interleukin 11 (IL-11), are required for optimal megakaryocyte development.
    Last edited by TomHsiung; Sat 3rd December '16 at 1:56pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

  2. #2
    PharmD Year 1 TomHsiung's Avatar
    Join Date
    Jan 2013
    Location
    Chengdu, Sichuan, China
    Posts
    593

    Default Normal Platelet Production

    Megakaryocyte proliferation and differentiation involve endomitosis and polyploidization, a process in which the nucleus divides but the cell does not. In the process of maturation, megakaryocytes form secretory granules and a demarcation membrane system that permeates the cytoplasmic space. This extensive membrane system eventually projects multiple filamentous pseudopodial structures called proplatelets. This process utilizes the entire repertoire of cytoplasmic granules, macromolecules, and membranes. Ultimately, fragmentation of the pseudopodial projections leads to the release of new platelets.

    However, the exact steps leading from megakaryocytes to mature platelets are still not fully resolved.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •