Platelets

Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. As a result, platelets have a diameter of 2–3 μm. Nuclei are not present; however, a variety of organelles are present and aid in different platelet functions.

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Overview

Definition

Platelets are small cell fragments without nuclei, but with a variety of organelles. Platelets are involved in primary hemostasis by adhering to damaged blood vessels and aggregating with one another (platelet plug).

Description:

  • Diameter: 2–3 µm 
  • Lens-shaped biconvex discoid
  • Normal count: 150,000–450,000 platelets/µL
  • Lifespan: up to 10 days

Structure

  • Outer membrane: Receptors facilitate platelet aggregation and adhesion to endothelial surfaces.
  • Open canalicular system: tunnels from membranes to platelet interior:
    • For entry of exterior elements
    • For granule release
    • For storage of glycoproteins
  • In the cytoplasm:
    • α granules (most abundant) contain: 
      • Proteins for primary hemostasis (e.g., integrin)
      • Proteins such as von Willebrand Factor (vWF), fibrinogen, factor V, and factor XI (needed for secondary hemostasis)
      • May have antiangiogenic-protein populations
      • May have proangiogenic-protein populations (e.g., vascular endothelial growth factor (VEGF))
    • δ granules contain:
      • Mediators of vascular tone: serotonin, calcium 
      • ADP and ATP
    • Lysosomes with hydrolytic enzymes:
      • Digest cytosolic contents
      • Participate in fibrinolysis and destruction of the extracellular matrix
  • The cytoskeleton (including actin, spectrin, tubulin, and filamin) is involved in:
    • Changing shape 
    • Motility towards the site of injury 
    • Granule release
  • Contains: the Golgi complex, elements of the rough endoplasmic reticulum (RER), mitochondria, and glycogen granules
Platelet Granule Exocytosis

Schematic diagram of a platelet:
The platelet is a 2–3 μm discoid cell containing α-granules, dense granules, lysosomes, and mitochondria. Tunnel invaginations of the plasma membrane form a complex membrane network, the open canalicular system, which courses throughout the platelet interior.

Image: “Platelet Granule Exocytosis” by Jennifer L Fitch-Tewfik and Robert Flaumenhaft. License: CC BY 3.0

Thrombopoiesis

Platelet production

  • Hematopoiesis location:
    • 1st–2nd month in utero: mesoderm of the yolk sac
    • 2nd month: liver and spleen
    • 5th month: bone marrow, which becomes the predominant source of blood cells
  • As with other blood cells, thrombopoiesis starts with multipotent hematopoietic stem cells (HSCs).
  • HSCs → multipotent progenitor (MPP) cells → common myeloid progenitor (CMP) or colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM) → fragmentation of megakaryocyte (platelets)
Bone marrow hematopoiesis

Production and differentiation of the cells in the bone marrow: Hematopoiesis or the production of all blood cells starts with a hematopoietic stem cell, which is prompted to divide and differentiate with appropriate chemical stimuli (hemopoietic growth factors).
CFU-GEMM: colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte
CFU-GM: colony-forming unit–granulocyte-macrophage
GM-CSF: granulocyte-macrophage colony-stimulating factor
M-CSF: macrophage colony-stimulating factor
G-CSF: granulocyte colony-stimulating factor
NK: natural killer
TPO: thrombopoietin

Image by Lecturio. License: CC BY-NC-SA 4.0

Stages of platelet development

Development takes 1 week on average:

  1. Megakaryoblast:
    • Basophilic cytoplasm with a large, ovoid-, or kidney-shaped nucleus
    • May have several nucleoli
  2. Megakaryocyte:
    • Giant cells (up to 150 μm in diameter)
    • Less basophilic
    • Long, branching cytoplasmic projections/extensions (proplatelets)
  3. Platelets: 
    • Results from megakaryocyte-cytoplasm fragmentation
    • Fragmented-cell remains become apoptotic and removed by macrophages.

Regulation

Table: Regulation
Cytokines/growth factorsActivitiesSource
Stem cell factor (SCF)Stimulates all hematopoietic progenitor cellsBone-marrow stromal cells
Granulocyte-macrophage colony-stimulating factor (GM-CSF)Stimulates myeloid progenitor cellsEndothelial cells, T cells
Thrombopoietin (TPO)Stimulates thrombopoiesisKidney, liver
Interleukin-3 (IL-3)Mitogen for all granulocyte and megakaryocyte-erythrocyte progenitor cellsT helper cells

Clinical Relevance

  • Thrombocytopenia: The patient presents with circulating platelets in the bloodstream below normal levels (< 150,000 platelets/µL).
  • Von Willebrand disease (vWD): The most frequently inherited bleeding disorder among humans. Von Willebrand factor (vWF) allows platelet aggregation and contributes to the formation of fibrin clots. Different types of vWD (types 1, 2, and 3) are based on qualitative or quantitative defects in vWF. The condition may also be acquired (e.g., lupus and myeloproliferative disorders). 
  • Essential thrombocythemia (ET): a myeloproliferative neoplasm characterized by the clonal thrombocytosis linked to somatic mutations involving JAK2, CALR, and MPL oncogene. The presentation can be complicated by thrombohemorrhagic events, and progression to myelofibrosis and acute myeloid leukemia. The diagnosis is by laboratory finding of thrombocytosis, bone-marrow biopsy, and genetic studies. Treatment aims to reduce platelet counts with cytoreductive agents (hydroxyurea) and decrease thrombosis with aspirin and systemic anticoagulation.

References

  1. Italiano Jr., J.E., Whiteheart, S.W., Bray, P.F., Li, Z., Coller, B.S., Smyth, S.S. (2021). Platelet morphology, biochemistry, and function. Kaushansky K., Prchal J.T., Burns L.J., Lichtman M.A., Levi M., Linch D.C. (Eds.), Williams Hematology, 10e. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2962&sectionid=252535907
  2. Kaushansky K. (2021). Megakaryopoiesis and thrombopoiesis. Kaushansky K., Prchal J.T., Burns L.J., Lichtman M.A., Levi M., Linch, D.C. (Eds.), Williams Hematology, 10e. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2962&sectionid=252535799
  3. Mescher, A.L. (Ed.), (2021). Hemopoiesis. Junqueira’s Basic Histology Text and Atlas, 16e. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=3047&sectionid=255121548
  4. Shin, E.K., Park, H., Noh, J.Y., Lim, K.M., Chung, J.H. (2017). Platelet Shape Changes and Cytoskeleton Dynamics as Novel Therapeutic Targets for Anti-Thrombotic Drugs. Biomolecules & Therapeutics, 25(3), 223–230. https://doi.org/10.4062/biomolther.2016.138
  5. Twomey, L., Wallace, R., Cummins, P., Degryse, B., Sheridan, S., Harrison, M., Moyna, N., Meade-Murphy, G., Navasiolava, N., Custaud, M., Murphy, R. (2018). Platelets: From Formation to Function, Homeostasis-An Integrated Vision, Fernanda Lasakosvitsch and Sergio Dos Anjos Garnes, IntechOpen. https://www.intechopen.com/books/homeostasis-an-integrated-vision/platelets-from-formation-to-function

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