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Bone marrow - nonneoplastic

Normal

Megakaryocytes


Reviewers: Dragos Luca, M.D. (see Reviewers page)
Revised: 16 October 2012, last major update August 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Progresses from myeloid stem cell (pluripotential hematopoietic stem cell) to megakaryoblast to promegakaryocyte to megakaryocyte to proplatelets (released into circulation) to platelets (J Thromb Haemost 2003;1:1580, Front Biosci 2007;12:2050)
● Two groups of factors influencing megakaryopoiesis are early acting multilineage cytokines (stem cell factor, GM-CSF, IL-3, IL-6) and cytokines that are more megakaryocyte-specific (thrombopoietin)
Thrombopoietin: produced by bone marrow stromal cells, hepatocytes and proximal renal tubular epithelial cells; poorly understood regulation
● Maturation is characterized by an increase in size and lobulation of nuclei and is controlled by thrombopoietin (J Clin Invest 2005;115:3339)
Endomitosis: unique property of megakaryocytes characterized by ongoing DNA synthesis, without mitosis resulting in progressive nuclear lobulation with increasing DNA content (nuclear lobes remain connected)
● Megakaryocytes form demarcation membrane within cytosol, which leads to production of platelets
● Maturation is associated with acquisition of surface GP Ib, GP IIb, and von Willebrand factor
● Four types of cytoplasmic granules are alpha, delta, gamma, and peroxisomes
● Megakaryocytes reside next to the bone marrow sinuses and project pseudopodia through the sinus walls, releasing platelets directly into the circulation

Clinical features
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● Megakaryocytes are smaller in fetuses and infants and show less nuclear segmentation when compared to older children
● Platelet production appears to be dependent on megakaryocyte ploidy
Platelet production rate under homeostatic conditions: 2-4 x 109/kg/day; may increase 8-10x if needed; 10 day survival time in peripheral blood
Emperipolesis: other cells, especially neutrophils, pass through megakaryoctye tubular system (due to its location) to enter the circulation
Thrombocytopenia with normal / increased megakaryocytes: congenital (Bernard-Soulier, May-Hegglin, gray platelet syndrome) or acquired (ITP, DIC, TTP, HUS, hypersplenism, megaloblastic anemia)
Thrombocytopenia with decreased megakaryocytes: congenital (Fanconi, thrombocytopenia with absent radii, X-linked amegakaryocytic thrombocytopenia, dyskeratosis congenita, Shwachman-Diamond) or acquired (aplastic anemia, bone marrow infiltration, infections, toxins, immune disorders)
Thrombocytosis: congenital (familial essential thrombocythemia, other familial myeloproliferative disorders) or acquired (reactive or neoplastic)

Diagrams
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Left-megakaryopoiesis pathways; right-proplatelet formation

Micro description
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Megakaryoblast: variable size (7-35 microns); may be designated micromegakaryoblast if < 15 microns; round / ovoid cells with scanty blue agranular cytoplasm that often forms a rim around nucleus, and may have a few small budding protrusions at periphery; nuclei are round / oval with coarse granular chromatin, one or more nucleoli
Megakaryocyte: randomly disbursed throughout bone marrow; 50-150 microns (largest normal nucleated cell in marrow); micromegakaryocytes measure 15-30 microns; abundant light blue to pink cytoplasm with numerous purple-red or pink granules; nucleus has 8, 16 or 32 overlapping lobes; no nucleolus; megakaryocytes producing platelets may have demarcated granular clumps of platelets streaming from the margins

Micro images
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Megakaryoblasts

           
Megakaryocytes

       
Emperipolesis

   
Left: CD34+ megakaryocytes (figures A, C, D); right: CD62P+ megakaryocyte

   
Left: promegakaryocyte; right: endomitosis

   
Platelet formation

Positive stains
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● CD41 and CD61 (surface and cytoplasmic)
● Also CD9, CD31, CD34, CD36, CD42a, CD42b, CD42c, CD42d, CD43, CD49b, CD49f, CD51, CD62P, CD110, CD111, CD112, CD141, CD151 and CD226 (Eur J Haematol 2005;74:228)

Negative stains
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● CD45, CD68

Electron microscopy images
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Platelets

Additional references
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J Clin Invest 2005;115:3348, J Clin Invest 2005;115:3332

End of Bone Marrow - nonneoplastic > Normal > Megakaryocytes


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