Megakaryocytopoiesis and Platelets

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HEMATOLOGY 2

MEGAKARYOCYTOPOIESIS AND PLATELETS

Hormones and Cytokines of Megakaryocytopoiesis

 Thrombopoietin

 Induce stem cell differentiation


 Induce proliferation and platelet release
 Found in kidney, liver and smooth muscles
 Circulates in the plasma
 Recombinant TPO
Table 13-3 Hormoones and Cytokines That Control Megakaryocytopoiesis

Cytokine/ Differentiation to Differentiation to Late Thrombocytopoiesis Clinical Use


Hormone Progenitors Megakaryocytes Maturation

TPO + + + 0 Available
IL-3 + + 0 - -
IL-6 0 0 + + -
IL-11 0 + + + Available

Three Stages of Megakaryocyte Progenitors


Cell Derived Stimulators of Megakaryocytopoiesis MEGAKARYOCYTOPOIESIS

 IL3 – for early differentiation of stem cells  Production and Development of


 IL 6 and 11 – act in the presence of TPO to Megakaryocytes
enhance endomitosis, megakaryocyte  Bone Marrow
maturation and platelet release.

Megakaryoblast or MK-I stage

 Cell size: 5-50 um


 Earliest recognizable stage of maturation
 Cell is irregular in shape hast blunt
protrusions (blebs) from its cytoplasmic
membrane
 Nucleus occupies most of the cell volume
 Has prominent nucleoli but rarely
marginated chromatin.
 Cytoplasmic ultrastructure
 Pro-coagulant-laden
 Alpha granules
 Dense Granules
 Demarcation System (DMS)
Platelets IMMUNOLOGIC TEST (FLOW CYTOMETRY)

 Non-nucleated, round to oval shape, 2-4um in


diameter.
 In times of decrease platelet compensatory
mechanism will occur
 Platelet Distribution:
 2/3 of platelets = in circulation
 1/3 of platelets = spleen

Promegakaryocyte or MK II stage

 Cell size: 20-80um


 Blunt protrusions are retained as well as
ribosomes
 Number of nuclear lobes INCREASE
 Cell is capable of protein synthesis thru DMS
 Cannot be distinguished by routine
examination.

Megakaryocyte or MK III stage

 Cell size: 30-100um


 Cytoplasm contains numerous small
granules, polyribosomes and mitochondria
 Nucleus is multi-lobulated and multi-
nucleatd
 The chromatin pattern is linear and coarse
 Aggregation of granular materials in
Endomitosis periphery of cytoplasm that represents
 It is a different form of mitosis DMS
 Lacks telophase and cytokinises  As it matures, it begins to contain all
 RUNX1 factor mediates the switch structural constituents of a mature
 Inhibits the Rho/ROCK pathways megakaryocytes
 Inadequate levels of actin and myosin
 Cytoplasmic constriction preventing
cytokines
Platelet shedding

 Outflowing of cytoplasm from the


megakaryocytes.
 Megakaryocyte matures in 5 days in the bone
marrow
 About 2,000-4,000 platelets produced per 1
megakaryocyte.
 MGK are not normally seen in the blood stream

Three Stages of Megakaryocyte Progenitors

 Stages
 Bfu-Meg – Least mature
 CFU-Meg
- Diploid, participate in Normal
mitosis
 LD – CFU Meg – able to do endomitosis

Note: All 3 resembles lymphocyte in BM WS smear

How to Identify? Immunologic Tests and Cytochemical


Stains

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