Skip to main content
SpringerLink
Log in

Platelets: Production, Morphology and Ultrastructure

  • Chapter
  • First Online:
Antiplatelet Agents

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 210))

Abstract

Platelets are anucleate, discoid cells, roughly 2–3 μm in diameter that function primarily as regulators of hemostasis, but also play secondary roles in angiogensis and innate immunity. Although human adults contain nearly one trillion platelets in circulation that are turned over every 8–10 days, our understanding of the mechanisms involved in platelet production is still incomplete. Platelets stem from large (30–100 μm) nucleated cells called megakaryocytes that reside primarily in the bone marrow. During maturation megakaryocytes extend long proplatelet elongations into sinusoidal blood vessels from which platelets ultimately release. During this process, platelets develop a number of distinguishable structural elements including: a delimited plasma membrane; invaginations of the surface membrane that form the open canalicular system (OCS); a closed-channel network of residual endoplasmic reticulum that form the dense tubular system (DTS); a spectrin-based membrane skeleton; an actin-based cytoskeletal network; a peripheral band of microtubules; and numerous organelles including α-granules, dense-granules, peroxisomes, lysosomes, and mitochondria. Proplatelet elongation and platelet production is an elaborate and complex process that defines the morphology and ultrastructure of circulating platelets, and is critical in understanding their increasingly numerous and varied biological functions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, Jin DK, Dias S, Zhang F, Hartman TE, Hackett NR, Crystal RG, Witte L, Hicklin DJ, Bohlen P, Eaton D, Lyden D, de Sauvage F, Rafii S (2004) Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med 10:64–71

    Article  PubMed  CAS  Google Scholar 

  • Balduini A, Pallotta I, Malara A, Lova P, Pecci A, Viarengo G, Balduini CL, Torti M (2008) Adhesive receptors, extracellular proteins and myosin IIA orchestrate proplatelet formation by human megakaryocytes. J Thromb Haemost 6:1900–1907

    Article  PubMed  CAS  Google Scholar 

  • Barkalow KL, Italiano JE Jr, Chou DE, Matsuoka Y, Bennett V, Hartwig JH (2003) Alpha-adducin dissociates from F-actin and spectrin during platelet activation. J Cell Biol 161:557–570

    Article  PubMed  CAS  Google Scholar 

  • Behnke O (1969) An electron microscope study of the rat megakaryocyte. II. Some aspects of platelet release and microtubules. J Ultrastruct Res 26:111–129

    Article  PubMed  CAS  Google Scholar 

  • Behnke O (1970) The morphology of blood platelet membrane systems. Ser Haematol 3:3–16

    PubMed  CAS  Google Scholar 

  • Behnke O, Forer A (1998) From megakaryocytes to platelets: platelet morphogenesis takes place in the bloodstream. Eur J Haematol Suppl 61:3–23

    PubMed  CAS  Google Scholar 

  • Blair P, Flaumenhaft R (2009) Platelet alpha-granules: basic biology and clinical correlates. Blood Rev 23:177–189

    Article  PubMed  CAS  Google Scholar 

  • Bluteau D, Lordier L, Di Stefano A, Chang Y, Raslova H, Debili N, Vainchenker W (2009) Regulation of megakaryocyte maturation and platelet formation. J Thromb Haemost 7(Suppl 1):227–234

    Article  PubMed  CAS  Google Scholar 

  • Brass LF, Hoxie JA, Manning DR (1993) Signaling through G proteins and G protein-coupled receptors during platelet activation. Thromb Haemost 70:217–223

    PubMed  CAS  Google Scholar 

  • Chen Z, Naveiras O, Balduini A, Mammoto A, Conti MA, Adelstein RS, Ingber D, Daley GQ, Shivdasani RA (2007) The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway. Blood 110:171–179

    Article  PubMed  CAS  Google Scholar 

  • Chen Z, Shivdasani RA (2009) Regulation of platelet biogenesis: insights from the May-Hegglin anomaly and other MYH9-related disorders. J Thromb Haemost 7(Suppl 1):272–276

    Article  PubMed  CAS  Google Scholar 

  • Choi ES, Nichol JL, Hokom MM, Hornkohl AC, Hunt P (1995) Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood 85:402–413

    PubMed  CAS  Google Scholar 

  • Coller BS, Seligsohn U, West SM, Scudder LE, Norton KJ (1991) Platelet fibrinogen and vitronectin in Glanzmann thrombasthenia: evidence consistent with specific roles for glycoprotein IIb/IIIA and alpha v beta 3 integrins in platelet protein trafficking. Blood 78:2603–2610

    PubMed  CAS  Google Scholar 

  • Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA (1996) Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. Blood 88:146–157

    PubMed  CAS  Google Scholar 

  • Flaumenhaft R (2003) Molecular basis of platelet granule secretion. Arterioscler Thromb Vasc Biol 23:1152–1160

    Article  PubMed  CAS  Google Scholar 

  • Folkman J, Browder T, Palmblad J (2001) Angiogenesis research: guidelines for translation to clinical application. Thromb Haemost 86:23–33

    PubMed  CAS  Google Scholar 

  • Freson K, De Vos R, Wittevrongel C, Thys C, Defoor J, Vanhees L, Vermylen J, Peerlinck K, Van Geet C (2005) The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure. Blood 106:2356–2362

    Article  PubMed  CAS  Google Scholar 

  • Handagama PJ, Feldman BF, Jain NC, Farver TB, Kono CS (1987) Circulating proplatelets: isolation and quantitation in healthy rats and in rats with induced acute blood loss. Am J Vet Res 48:962–965

    PubMed  CAS  Google Scholar 

  • Hartwig JH, DeSisto M (1991) The cytoskeleton of the resting human blood platelet: structure of the membrane skeleton and its attachment to actin filaments. J Cell Biol 112:407–425

    Article  PubMed  CAS  Google Scholar 

  • Hartwig JH, Barkalow K, Azim A, Italiano J (1999) The elegant platelet: signals controlling actin assembly. Thromb Haemost 82:392–398

    PubMed  CAS  Google Scholar 

  • Hartwig JH, Italiano JE Jr (2006) Cytoskeletal mechanisms for platelet production. Blood Cells Mol Dis 36:99–103

    Article  PubMed  CAS  Google Scholar 

  • Heemskerk JW, Bevers EM, Lindhout T (2002) Platelet activation and blood coagulation. Thromb Haemost 88:186–193

    PubMed  CAS  Google Scholar 

  • Heijnen HF, Debili N, Vainchencker W, Breton-Gorius J, Geuze HJ, Sixma JJ (1998) Multivesicular bodies are an intermediate stage in the formation of platelet alpha-granules. Blood 91:2313–2325

    PubMed  CAS  Google Scholar 

  • Howell WH, Donahue DD (1937) The production of blood platelets in the lungs. J Exp Med 65:177–203

    Article  PubMed  CAS  Google Scholar 

  • Italiano JE Jr, Lecine P, Shivdasani RA, Hartwig JH (1999) Blood platelets are assembled principally at the ends of proplatelet processes produced by differentiated megakaryocytes. J Cell Biol 147:1299–1312

    Article  PubMed  CAS  Google Scholar 

  • Italiano JE Jr, Bergmeier W, Tiwari S, Falet H, Hartwig JH, Hoffmeister KM, Andre P, Wagner DD, Shivdasani RA (2003) Mechanisms and implications of platelet discoid shape. Blood 101:4789–4796

    Article  PubMed  CAS  Google Scholar 

  • Italiano JE Jr, Patel-Hett S, Hartwig JH (2007) Mechanics of proplatelet elaboration. J Thromb Haemost 5(Suppl 1):18–23

    Article  PubMed  CAS  Google Scholar 

  • Italiano JE Jr, Richardson JL, Patel-Hett S, Battinelli E, Zaslavsky A, Short S, Ryeom S, Folkman J, Klement GL (2008) Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood 111:1227–1233

    Article  PubMed  CAS  Google Scholar 

  • Jones OP (1960) Origin of megakaryocyte granules from Golgi vesicles. Anat Rec 138:105–113

    Article  PubMed  CAS  Google Scholar 

  • Junt T, Schulze H, Chen Z, Massberg S, Goerge T, Krueger A, Wagner DD, Graf T, Italiano JE Jr, Shivdasani RA, von Andrian UH (2007) Dynamic visualization of thrombopoiesis within bone marrow. Science 317:1767–1770

    Article  PubMed  CAS  Google Scholar 

  • Kaushansky K (2006) Lineage-specific hematopoietic growth factors. N Engl J Med 354:2034–2045

    Article  PubMed  CAS  Google Scholar 

  • Kenney DM, Linck RW (1985) The cystoskeleton of unstimulated blood platelets: structure and composition of the isolated marginal microtubular band. J Cell Sci 78:1–22

    PubMed  CAS  Google Scholar 

  • Kovacsovics TJ, Hartwig JH (1996) Thrombin-induced GPIb-IX centralization on the platelet surface requires actin assembly and myosin II activation. Blood 87:618–629

    PubMed  CAS  Google Scholar 

  • Larson MK, Watson SP (2006a) A product of their environment: do megakaryocytes rely on extracellular cues for proplatelet formation? Platelets 17:435–440

    Article  PubMed  CAS  Google Scholar 

  • Larson MK, Watson SP (2006b) Regulation of proplatelet formation and platelet release by integrin alpha IIb beta3. Blood 108:1509–1514

    Article  PubMed  CAS  Google Scholar 

  • Lecine P, Villeval J, Vyas P, Swencki B, Yuhui X, Shivdasani RA (1998) Mice lacking transcription factor NF-E2 provide in vivo validation of the proplatelet model of thrombocytopoiesis and show a platelet production defect that is intrinsic to megakaryocytes. Blood 92:1608–1616

    PubMed  CAS  Google Scholar 

  • Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, Gachet C, Bader M, Clavien PA (2006) Platelet-derived serotonin mediates liver regeneration. Science 312:104–107

    Article  PubMed  CAS  Google Scholar 

  • Leven RM (1987) Megakaryocyte motility and platelet formation. Scanning Microsc 1:1701–1709

    PubMed  CAS  Google Scholar 

  • Mazharian A, Ghevaert C, Zhang L, Massberg S, Watson SP (2011a) Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation. Blood 117(19):5198–5206

    Article  PubMed  CAS  Google Scholar 

  • Mazharian A, Thomas SG, Dhanjal TS, Buckley CD, Watson SP (2011b) Critical role of Src-Syk-PLC{gamma}2 signaling in megakaryocyte migration and thrombopoiesis. Blood 116:793–800

    Article  Google Scholar 

  • Michelson AD (1992) Thrombin-induced down-regulation of the platelet membrane glycoprotein Ib-IX complex. Semin Thromb Hemost 18:18–27

    Article  PubMed  CAS  Google Scholar 

  • Nachmias VT, Yoshida K-I (1988) The cytoskeleton of the blood platelet: a dynamic structure. Adv Cell Biol 2:181–211

    Article  Google Scholar 

  • Nagahisa H, Nagata Y, Ohnuki T, Osada M, Nagasawa T, Abe T, Todokoro K (1996) Bone marrow stromal cells produce thrombopoietin and stimulate megakaryocyte growth and maturation but suppress proplatelet formation. Blood 87:1309–1316

    PubMed  CAS  Google Scholar 

  • Nakao K, Angrist AA (1968) Membrane surface specialization of blood platelet and megakaryocyte. Nature 217:960–961

    Article  PubMed  CAS  Google Scholar 

  • Nilsson SK, Debatis ME, Dooner MS, Madri JA, Quesenberry PJ, Becker PS (1998) Immunofluorescence characterization of key extracellular matrix proteins in murine bone marrow in situ. J Histochem Cytochem 46:371–377

    Article  PubMed  CAS  Google Scholar 

  • Ogawa M (1993) Differentiation and proliferation of hematopoietic stem cells. Blood 81:2844–2853

    PubMed  CAS  Google Scholar 

  • Patel-Hett S, Wang H, Begonja AJ, Thon JN, Alden EC, Wandersee NJ, An X, Mohandas N, Hartwig JH, Italiano JE Jr (2011) The spectrin-based membrane skeleton stabilizes mouse megakaryocyte membrane systems and is essential for proplatelet and platelet formation. Blood 118(6):1641–1652

    Article  PubMed  CAS  Google Scholar 

  • Patel SR, Hartwig JH, Italiano JE Jr (2005a) The biogenesis of platelets from megakaryocyte proplatelets. J Clin Invest 115:3348–3354

    Article  PubMed  CAS  Google Scholar 

  • Patel SR, Richardson JL, Schulze H, Kahle E, Galjart N, Drabek K, Shivdasani RA, Hartwig JH, Italiano JE Jr (2005b) Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes. Blood 106:4076–4085

    Article  PubMed  CAS  Google Scholar 

  • Radley JM, Scurfield G (1980) The mechanism of platelet release. Blood 56:996–999

    PubMed  CAS  Google Scholar 

  • Radley JM, Haller CJ (1983) Fate of senescent megakaryocytes in the bone marrow. Br J Haematol 53:277–287

    Article  PubMed  CAS  Google Scholar 

  • Ravid K, Lu J, Zimmet JM, Jones MR (2002) Roads to polyploidy: the megakaryocyte example. J Cell Physiol 190:7–20

    Article  PubMed  CAS  Google Scholar 

  • Richardson JL, Shivdasani RA, Boers C, Hartwig JH, Italiano JE Jr (2005) Mechanisms of organelle transport and capture along proplatelets during platelet production. Blood 106:4066–4075

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg S, Stracher A, Lucas RC (1981) Isolation and characterization of actin and actin-binding protein from human platelets. J Cell Biol 91:201–211

    Article  PubMed  CAS  Google Scholar 

  • Safer D, Nachmias VT (1994) Beta thymosins as actin binding peptides. Bioessays 16:590

    Article  PubMed  CAS  Google Scholar 

  • Schwer HD, Lecine P, Tiwari S, Italiano JE Jr, Hartwig JH, Shivdasani RA (2001) A lineage-restricted and divergent beta-tubulin isoform is essential for the biogenesis, structure and function of blood platelets. Curr Biol 11:579–586

    Article  PubMed  CAS  Google Scholar 

  • Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJ, Orkin SH (1995) Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell 81:695–704

    Article  PubMed  CAS  Google Scholar 

  • Shivdasani RA (2001) Molecular and transcriptional regulation of megakaryocyte differentiation. Stem Cells 19:397–407

    Article  PubMed  CAS  Google Scholar 

  • Stenberg PE, Levin J (1989) Mechanisms of platelet production. Blood Cells 15:23–47

    PubMed  CAS  Google Scholar 

  • Tablin F, Castro M, Leven RM (1990) Blood platelet formation in vitro. The role of the cytoskeleton in megakaryocyte fragmentation. J Cell Sci 97(Pt 1):59–70

    PubMed  Google Scholar 

  • Thon JN, Montalvo A, Patel-Hett S, Devine MT, Richardson JL, Ehrlicher A, Larson MK, Hoffmeister K, Hartwig JH, Italiano JE Jr (2011) Cytoskeletal mechanics of proplatelet maturation and platelet release. J Cell Biol 191:861–874

    Article  Google Scholar 

  • Tucker EI, Marzec UM, Berny MA, Hurst S, Bunting S, McCarty OJ, Gruber A, Hanson SR (2010) Safety and antithrombotic efficacy of moderate platelet count reduction by thrombopoietin inhibition in primates. Sci Transl Med 2:37ra45

    Article  PubMed  Google Scholar 

  • van Nispen Tot Pannerden H, de Haas F, Geerts W, Posthuma G, van Dijk S, Heijnen HF (2010) The platelet interior revisited: electron tomography reveals tubular alpha granule subtypes. Blood 116(7):1147–1156

    Article  PubMed  Google Scholar 

  • White JG (1968) Effects of colchicine and Vinca alkaloids on human platelets. I. Influence on platelet microtubules and contractile function. Am J Pathol 53:281–291

    PubMed  CAS  Google Scholar 

  • White JG (1972) Interaction of membrane systems in blood platelets. Am J Pathol 66:295–312

    PubMed  CAS  Google Scholar 

  • Yin T, Li L (2006) The stem cell niches in bone. J Clin Invest 116:1195–1201

    Article  PubMed  CAS  Google Scholar 

  • Youssefian T, Cramer EM (2000) Megakaryocyte dense granule components are sorted in multivesicular bodies. Blood 95:4004–4007

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the National Institutes of Health grant Hl68130 (JEI). JEI is an American Society of Hematology Junior Faculty Scholar. JNT is an American Society of Hematology Scholar.

Author information

Authors and Affiliations

  1. Department of Medicine, Brigham and Women’s Hospital, 1 Blackfan Circle, Karp 6, Boston, MA, USA

    Jonathan N. Thon Ph.D. & Joseph E. Italiano Ph.D.

  2. Harvard Medical School, Boston, MA, USA

    Jonathan N. Thon Ph.D. & Joseph E. Italiano Ph.D.

  3. Department of Surgery, Vascular Biology Program, Children’s Hospital, Boston, MA, USA

    Joseph E. Italiano Ph.D.

Authors
  1. Jonathan N. Thon Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph E. Italiano Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph E. Italiano Ph.D. .

Editor information

Editors and Affiliations

  1. , Department of Internal Medicine, University of Perugia, Via E. dal Pozzo, Perugia, 06126, Italy

    Paolo Gresele

  2. Institute, The William Harvey Research, Charterhouse Square, London, EC1M6BQ, United Kingdom

    Gustav V. R Born

  3. Istituto di Farmacologia, Università Cattolica del S. Cuore, Largo F. Vito 1, Roma, 00168, Italy

    Carlo Patrono

  4. King's College London, Sackler Inst. Pulmonary Pharmacology, Waterloo Campus, London, SE1 9NH, United Kingdom

    Clive P. Page

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Thon, J.N., Italiano, J.E. (2012). Platelets: Production, Morphology and Ultrastructure. In: Gresele, P., Born, G., Patrono, C., Page, C. (eds) Antiplatelet Agents. Handbook of Experimental Pharmacology, vol 210. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29423-5_1

Download citation

Publish with us

Policies and ethics

Search

Navigation