Thrombopoiesis : Thrombopoiesis Presented by 4/11/2012 Faisal Ashfaq What are platelets ? : What are platelets ? Platelets are small,regularly shaped clear cell fragments ranging from 2 - 3 micro meter in diameter i.e about 20% of diameter of red blood cells.
The normal platelet count is
150,000 – 400,000 /microlitre of blood.
They are Derived from fragmentation of precursor megakaryocytes.
The average life span of a platelet is just about 5 – 9 days .
They are shaped like a plate ,therefore their name.but when platelets are activated or stimulated by a breakage in blood vessel wall ,they turn into a
“ stellate” shape which is like a star shape having rays or projections radiating from the centre.these projecting arms help the platelets to make a plug to seal the broken blood vessel. 4/11/2012 Slide 3: 4/11/2012 Slide 4: 4/11/2012 Sequential access of mechanism : Sequential access of mechanism Totipotent stem cell
platelets 4/11/2012 Totipotent stem cell : Totipotent stem cell Stem cells are cells found in all multi cellular organisms. They are characterized by the ability to renew themselves through mitotic cell division and differentiate into a diverse range of specialized cell types. 4/11/2012 Stem cells with fluorescent marker : Stem cells with fluorescent marker 4/11/2012 A.cells not yet differentiated B.differentiated nerve cells : A.cells not yet differentiated B.differentiated nerve cells 4/11/2012 megakaryoblasts : megakaryoblasts A megakaryoblast is a precursor cell to a promegakaryocyte, which in turn becomes a megakaryocyte .It is the beginning of the thrombocytic series.
It derives from "CFU-Meg" (megakaryocyte colony forming units)
Megakaryoblast cells show cytoplasmic granulations. 4/11/2012 1 Megakaryoblast and 1 binucleated megakaryocyte : 1 Megakaryoblast and 1 binucleated megakaryocyte 4/11/2012 Four megakaryoblasts:all show cytoplasmic granulaton. : Four megakaryoblasts:all show cytoplasmic granulaton. 4/11/2012 promegakaryocytes : promegakaryocytes Promegakaryocytes are larger than their precursor cells b/c of “endoreduplication” i.e nuclear replication without dividing of the cell.
Such replication leads them to attain a larger size.
Their cytoplasm contain basophilic granules.
The means or process of formation of platelets from mrgakaryocytes is still unclear.but its thought to be happened that
“megakaryocyte buds off its cytoplasm to form platelets containing small granules”. 4/11/2012 Megakaryocytes : Megakaryocytes They are the unique cells in that they increase their nuclear DNA content wihtin the same nucleus.
Their size ranging from 30 – 90 micrometer.
They contain 4 – 16 nuclear lobes.
Their cytoplasm contains many small red-purple granules 4/11/2012 a.Megakaryocyte with nuclear lobes b.two megakaryocytes in bone maeeow : a.Megakaryocyte with nuclear lobes b.two megakaryocytes in bone maeeow 4/11/2012 Mechanism : Mechanism Platelets are formed by protrusions into the bone marrow sinusoids of pseudopods of megakaryocyte cytoplasm which detach into the blood stream and fragment to yield small discoid platelets.
This explains the process that how the non-motile platelets enter the circulation.
Each megakaryocyte produces about 1000 platelets.
The means or process of formation of platelets from megakaryocytes is still unclear.
But its thought to be happened that megakaryocyte buds off its cytoplasm and gives rise to platelets containing small granules. 4/11/2012 Slide 16: 4/11/2012 Slide 17: 4/11/2012 Slide 18: The formation of platelets might be under hormonal controll the “thrombopoietin “(TPO)
But its role is still subjective.however,its stated that the controll mechanism of platelet production is likely to be complex and involve more than one chemical messangers.
For instance,heterodimeric erythroid transcription factor NF-E2 is thought to be an essential factor for megakaryocyte maturation and platelet production. 4/11/2012 Two alternative proposals about platelet formation : Two alternative proposals about platelet formation 1.Its thought that platelets are preformed wihtin the megakaryocytes by “Demarcation membrane system”.
>Demarcation membrane system is a series of membranes extending throughout the cytoplasm over the mature megakaryocytes.
2.Megakaryocyte cytoplasm undergoes sequential binary divisions,an idea supported by computer model. 4/11/2012 Cytoskeletal mechanism for platelet maturation : Cytoskeletal mechanism for platelet maturation Platelets release from megakaryocytes living primarily in the bone marrrow space. Intermediates in platelet formation are proplatelets, long tube-like processes that are extended by microtubule-based forces hundreds of micrometers from the megakaryocyte cell body. Granules and organelles enter the proplatelets and traffic up and down on their microtubules to be ultimately delivered to the platelet buds before they release. How individual platelets form and release from proplatelets remains poorly understood. 4/11/2012 Vascular concentration ofplatelets : Vascular concentration ofplatelets Platelet concentration in vascular compartment is regulated by feedback mechanism i.e platelet production is increased in response to destruction or removal of platelets and their production decreases in response to the infusion of platelets. 4/11/2012 Clinical aspects : Clinical aspects 4/11/2012 Over production : Over production Excess production of platelets than normal results in thrombosis,causing blood clotting,obstructing blood vessels and so can be the result of
Etc… 4/11/2012 Deficiency effects : Deficiency effects The symptoms of redused platelet production (thrombocytopenia) can be
Excessive bleeding after being cut
Heavy menstrual flow
Bleeding in mouth
Bone marrow disease such as “leukemia” can also cause thrombocytopenia.
HIV can also cause low platelet count. 4/11/2012 Slide 25: 4/11/2012 Thanks : Thanks REMEMBER IN PRAYERS 4/11/2012