The biogenesis of platelets from megakaryocyte proplatelets

Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Journal of Clinical Investigation (Impact Factor: 13.77). 01/2006; 115(12):3348-54. DOI: 10.1172/JCI26891
Source: PubMed

ABSTRACT Platelets are formed and released into the bloodstream by precursor cells called megakaryocytes that reside within the bone marrow. The production of platelets by megakaryocytes requires an intricate series of remodeling events that result in the release of thousands of platelets from a single megakaryocyte. Abnormalities in this process can result in clinically significant disorders. Thrombocytopenia (platelet counts less than 150,000/microl) can lead to inadequate clot formation and increased risk of bleeding, while thrombocythemia (platelet counts greater than 600,000/microl) can heighten the risk for thrombotic events, including stroke, peripheral ischemia, and myocardial infarction. This Review will describe the process of platelet assembly in detail and discuss several disorders that affect platelet production.

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    • "Platelets are formed and released into the bloodstream by precursor cells called megakaryocytes (MK) that are derived from haematopoietic stem cells (HSCs), which evolve from the multipotential haemangioblast. Mature MKs give rise to circulating platelets by the acquisition of the cytoplasmic structural and functional characteristics necessary for platelet action [1] [2], reaching cell sizes <50–100 microns in diameter and ploidy ranging up to 128 N [3] [4]. Endoreduplication (polyploidisation) and expansion of cytoplasmic mass are the hallmarks of MK maturation [5]. "
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    ABSTRACT: Background: Thrombocytopenia (platelet counts less than 150,000/μl) is commonly encountered in various hematological disorders including myelodysplastic syndromes as well as various non-myelodysplastic hematological conditions. Aim: The present study was undertaken to calculate the prevalence of various conditions associated with thrombocytopenia and to record the megakaryocytic alterations in various cases of thrombocytopenia. Apart from this by means of statistical analysis it was tried to analyze whether a significant difference existed in megakaryocytic alteration noted in myelodysplastic versus non- myelodysplastic conditions. Materials and Methods: A prospective series of 60 bone marrow aspirations along with concomitant bone marrow biopsies was conducted in a tertiary care centre catering to both urban as well as rural population in north India. Statistical Analysis: The distribution of morphological changes in cases of non myelodysplastic conditions and myelodysplastic were compared using Chi-Square test. A p-value less than 0.05 was considered significant. Results: The commonest cause of thrombocytopenia for which bone marrow examination was sought was dimorphic anaemia (18 cases, 30%), followed by myelodysplastic syndrome (06 cases, 10%) which was followed equally by acute lymphocytic leukemia and blast crisis of chronic myeloid leukemia (CML). Of all the non-MDS conditions apart from dimorphic anaemia, idiopathic thrombocytopenic purpura and chronic myeloid leukemia (blast crisis); megakaryocytic dysplastic forms were not noted in any other condition. In cases of myelodysplasia; dysplastic forms, bare megakaryocytic nuclei, hypogranular forms and micromegakaryocytes were seen. Comparison between frequencies of normal, high and low number of nuclear lobes among MDS (n=9) and non MDS (n=68) conditions were found to be statistically significant. Conclusion: Further studies on the evaluation of megakaryocytic alteration and their contribution to thrombocytopenia can provide growing knowledge to the pathogenesis of numerous hematopoietic disorders that may identify broader clinical applications of the newer strategies to regulate platelet count and functioning.
    03/2013; 7(3):473-9. DOI:10.7860/JCDR/2013/5085.2801
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    • "They become polyploid (4–64 N) through several cycles of endomitosis [6] [7] [8]. In addition, a cytoplasmic maturation occurs involving the formation of a demarcation membrane system (DMS) and the accumulation of cytoplasmic proteins and secretory granules [6] [9]. "
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    ABSTRACT: Platelets play an important role in the pathogenesis and the ischemic complications of atherosclerosis. Platelets may be activated by several different agonists, promoting the release of their granule contents and subsequent aggregation and thrombus formation; this leads to ischemic events such as myocardial infarction or stroke. Aspirin, the most popular antiplatelet agent, is a cornerstone in the treatment and prevention of ischemic events in cardiovascular patients. It inhibits a particular amplification pathway of platelet activation, based on thromboxane A2 (TxA2) generation. However, despite a consistent inhibition of TxA2 production, a substantial proportion of patients display preserved platelet function. This phenotype is defined as “high on-treatment platelet reactivity”. It is a risk factor for the recurrence of ischemic events, particularly in acute vessel injury settings. The determinants of platelet reactivity in these patients remain unclear, but previous studies, including healthy subjects, suggested that it is genetically determined. Over the last decade, technological improvements have led to the development of highly efficient omics strategies. High-throughput genomics, transcriptomics and proteomics have the potential to dissect fine metabolic modulations. However, the bioinformatics management of these large data sets remains a challenging issue. Network biology approaches permit the integration of different omics data sets and the identification of mutual interactions between gene products and/or molecules. The inherent topology of the network can be then explored at a pathway level rather than at a gene level. Network biology constitutes an efficient tool to further explore platelet metabolism and defects, such as modulators of platelet reactivity in cardiovascular patients.
    01/2013; 1(1):25-37. DOI:10.1016/j.trprot.2013.04.002
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    • "Blood platelets arise from megakaryocytes. Megakaryocytes undergo elongation of plasma membrane to form protrusions called proplatelets into the bone marrow sinusoid vessels [82] [85] [97] [98]. When exposed to shear forces form the blood flow, proplatelets release preplatelets, then platelets, into the circulation [85] [99]. "
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    ABSTRACT: Remodeling of the membrane and cytoskeleton is involved in a wide range of normal and pathologic cellular function. These are complex, highly-coordinated biochemical and biophysical processes involving dozens of proteins. Serving as a scaffold for a variety of proteins and possessing a domain that interacts with plasma membranes, the BAR family of proteins contribute to a range of cellular functions characterized by membrane and cytoskeletal remodeling. There are several subgroups of BAR proteins: BAR, N-BAR, I-BAR, and F-BAR. They differ in their ability to induce angles of membrane curvature and in their recruitment of effector proteins. Evidence is accumulating that BAR proteins contribute to cancer cell invasion, T cell trafficking, phagocytosis, and platelet production. In this review, we discuss the physiological function of BAR proteins and discuss how they contribute to blood and cancer disorders.
    01/2012; 3(2):198-208.
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