The main physiological function of megakaryocytes is the production of platelets, whose development, maturation and platelet production are a complex regulatory process, and are involved in many factors. In recent years it was found that the lung is also the main site of megakaryocyte-producing platelets in addition to bone marrow. Based on the findings of recent years, this review summarizes the process of megakaryocyte development, maturation and platelet production, with emphasis on the analyzing the regulatory effects of apoptotic factors, miRNA, thrombopoietin and its receptors, interleukins, transcription factors and their corresponding signal pathways on platelet production. To understand the regulatory mechanism of platelet production can help to understand the pathological mechanism of platelet-related diseases and provide new ideas for the diagnosis and treatment of platelet-related diseases.
Blood Platelets ; Bone Marrow Cells ; Megakaryocytes ; Thrombopoiesis ; Thrombopoietin

Tubulin affects platelets count through the control of mitosis and the formation of pro-platelets during the maturation of megakaryoblast to platelets. Tubulin is involved in maintaining the integrity of platelet skeleton, and also participates in the change of platelet morphology during platelet activation. Some new anti-tumor drugs targeting cell mitosis are trying to reduce the effect on tubulin in order to reduce the side effect of drugs on platelet formation. In some patients with thrombocytopenia, the variation and polymorphism of the tubulin gene affect the structure of microtubule multimers, which leads to the decrease of platelet formation. This review summarized the latest progresses of tubulin in the regulation of megakaryopoiesis and thrombopoiesis.
Blood Platelets ; Humans ; Megakaryocytes ; Platelet Count ; Thrombopoiesis ; Tubulin

Cyclic thrombocytopenia is a rare disorder with cyclic change of the platelet counts. Although the pathogenesis of the disorder has not been clarified, recent reports suggest that periodic destruction and/or ineffective production of platelets may be important causes of the disease. We report a 24-year-old female with the episodes of severe thrombocytopenia (minimum platelet count 2x109/L) followed by normal or higher platelet counts (maximum platelet count 877x109/L). The period of platelet count fluctuation was about 20-40 days. Morphological examination of bone marrow showed the cyclic disappearance of mature and immature megakaryocytes. These findings indicate that the cause of platelet fluctuation is periodic failure of megakaryocytopoiesis.
Blood Platelets ; Bone Marrow ; Female ; Humans ; Megakaryocytes ; Platelet Count ; Thrombocytopenia* ; Thrombopoiesis ; Young Adult

BACKGROUND: Analysis of reticulated platelets (RPs) is useful for discriminating the causes of thrombocytopenia and monitoring the thrombopoiesis. In the patients with severe thrombocytopenia, we evaluated the thrombopoiesis-discriminating ability of several indices applying forward scatter (FSC) and thiazole orange (TO) fluorescence in addition to the percentage of reticulated platelets (RPs%). METHODS: Forty cases with decreased thrombopoiesis, twenty cases with increased thrombopoiesis and twenty cases with liver cirrhosis were selected. By flow cytometry with two analytic methods, dependent on or independent of the staining of CD41-PE as a platelet marker, the primary parameters including RPs% were measured and the applied parameters were calculated from them. And we compared the diagnostic efficiency of each parameter and analyzed the purity of platelet light scatter gate. RESULTS: The purity of platelet light scatter gate was significantly lower in patients with severe thrombocytopenia than in healthy persons with normal platelet counts (P<10(-6)), so the use of CD41-PE for platelet gating improved the diagnostic efficiency of RPs%. Compared to the primary parameters, the applied parameters originated from RPs%, FSC and TO fluorescence improved diagnostic efficiency significantly (RPs%: 55%, RPs%xs delta MFI: 80%) between decreased and increased thrombopoiesis groups. CONCLUSIONS: In the patients with severe thrombocytopenia, the estimate of the thrombopoiesis by a flow cytometric analysis can be more predictable by using platelet markers and by considering the fluorescence intensity of TO together with the RPs%.
Blood Platelets ; Citrus sinensis ; Flow Cytometry ; Fluorescence ; Humans ; Liver Cirrhosis ; Platelet Count ; Thrombocytopenia* ; Thrombopoiesis*

BACKGROUND: Measurement of reticulated platelets (RPs) is useful in order to discriminate the causes of thrombocytopenia. In flow cytometric analysis for the percentage of RPs (RPs%), only thiazole orange (TO) fluorescence is considered, ignoring the significance of forward scatter (FSC). In this study, we intended to devise a new index reflecting the pattern of platelet clusters in the plot of FSC vs. TO fluorescence. METHODS: In the patients with moderate thrombocytopenia, 44 cases with decreased thrombopoiesis and 37 cases with increased thrombopoiesis were selected. In flow cytometry, several indices made with FSC and TO fluorescence were evaluated in discrimination between the two groups. RESULTS: Of the primary parameters, RPs% and FSC had relatively high efficiencies in discrimination. A new index incorporating these two parameters had higher efficiency than RPs% (P<0.05). New index=RPs%x(TO-positive platelet FSC-TO-negative platelet FSC)/TO-negative platelet FSC) CONCLUSIONS: In addition to the RPs%, more information about thrombopoiesis was obtained through the analysis of the plot of FSC vs. TO fluorescence and the index that quantifies the pattern of TOstained platelet clusters was devised.
Blood Platelets ; Citrus sinensis ; Discrimination (Psychology) ; Flow Cytometry ; Fluorescence ; Humans ; Thrombocytopenia* ; Thrombopoiesis*

Immune thrombocytopenia (ITP) is a common acquired autoimmune hematological disorders. Platelet autoantibodies lead to the decrease of platelet production and (or) increase of its destruction. The latest researches showed that the abnormal tryptophan metabolism mediated by indoleamine-2, 3-dioxygenase(IDO) is related with the pathogenesis of ITP. The patients with ITP show less expression of IDO, reduction of Treg cells and increase of autoreactive T cells and autoantibodies. CTLA-4-Ig can improve the expression of IDO in the patients with ITP, which also can inhibit the proliferation and activation of self-reactive T cells. Thus, clarifying the abnormal tryptophan metabolism mediated by IDO may provide a new idea for improving the understand of the pathogenesis and treatment of ITP. This review focuses on reasearch progress of the tryptophan metabolism mediated by IDO and ITP.
Autoantibodies ; Blood Platelets ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Thrombocytopenia ; Thrombopoiesis ; Tryptophan

This study is designed to detect the emperipolesis in megakaryocyte in fetal liver, which is an important organ of hemopoiesis, during rat development, and to compare the activity of erythropoiesis in fetal liver with that of emperipolesis in megakaryocyte. In order to find that which causes are more related to emperipolesis, we applied periodic acid Schiff reagent, which is special staining method for megakaryocyte and used electron microscope. The size and maturity of magakaryocyte gradually developed with age. The number of megakaryocyte increased in similar proportion to the activity of erythropoiesis. Emperipolesis occurred in more mature megakaryocyte (most stage III). The majority of cells enclosed within megakaryocyte, were the precursor of erythrocytes. Emperipolesis was observed for the first time at 14 day of gestation. The highest frequency of emperipolesis showed 20% of whole megakaryocyte at 16 day of gestation, when the activity of erythropoiesis was most vigorous. The frequency of emperipolesis began to decrease after then, but megakaryocyte was most numerous at 17 day of gestation during fetal and neonatal period. At 19 day of gestation, stage IV megakaryocytes, just before the stage producing platelet, began to appear. Megakaryocyte was not observed after postnatal 10 day. In conclusion, it was found that the emperipolesis in megakaryocyte occurred in the rat fetal liver and was extreme the emperipolesis most observed at the time of most vigorous erythropoiesis during the development of rat fetal liver. It is suggested that the frequency of emperipolesis within megakaryocyte is more closely related with the activity of erythropoiesis in fetal liver than the that of megakaryocytopoiesis, before bone marrow acts as an important organ of hematopoiesis. It is also suggested that the emperipolesis contributes to the production of platelet during gestation period and the maturation of erythrocyte.
Animals ; Blood Platelets ; Bone Marrow ; Emperipolesis* ; Erythrocytes ; Erythropoiesis ; Hematopoiesis ; Liver ; Megakaryocytes* ; Periodic Acid ; Pregnancy ; Rats ; Thrombopoiesis

PURPOSE: We performed this study to determine the diagnostic significance and useful cut-off value of reticulated platelet, which can be used for discriminating the destructive thrombocytopenia from underproductive thrombocytopenia. METHODS: We evaluated 37 patients with thrombocytopenia who were admitted to the Wonju christian hospital from March to July, 1995. All patients were evaluated with bone marrow megakaryocyte count. We divided them into two groups, group 1 was consisted of underproductive thrombocytopenic patients and group 2 was consisted of destructive thrombocytopenic patients. We measured the peripheral blood reticulated platelet count by FACScan flowcytometry after thiazole orange staining. RESULTS: 1) Among 37 patients, underproductive group consisted of 21 patients and destructive group consisted of 16 patients. 2) There was no significant difference in platelet count between two groups (41.7 31.8x109/L vs. 41.0 29.1x109/L). 3) Destructive group showed higher reticulated platelet count than underproductive group (7.7 3.7% vs. 19.1 11.1% : p<0.01). 4) Ideal cut-off value of reticulated platelet count for the discrimination of two groups was 11%. Its sensitivity and specificity were 88% and 95%, respectively. CONCLUSIONS: We suggest that reticulated platelet count is closely correlated with thrombopoiesis of bone marrow. The measurement of reticulated platelet can be a simple and useful diagnostic tool to discriminate destructive thrombocytopenia from underproductive thrombocytopenia.
Blood Platelets* ; Bone Marrow ; Citrus sinensis ; Discrimination (Psychology) ; Gangwon-do ; Humans ; Megakaryocytes ; Platelet Count ; Sensitivity and Specificity ; Thrombocytopenia* ; Thrombopoiesis

5-hydroxtryptamine (5-HT, serotonin) has been recognized not only as a neurotransmitter and vasoactive agent, but also as a growth factor. 5-HT mainly binds to 5-HT(2) receptors or 5-HT(1) receptors on cell surface to stimulate cell proliferation through Ras or MAPK pathway in many cell types. It has been reported that 5-HT stimulates megakaryocytopoiesis via 5-HT receptors. The possible mechanism of 5-HT on the proliferation and differentiation of megakaryocytes (MK) has been discussed in this review article. In early stage of megakaryocytopoiesis, 5-HT may bind to 5-HT(2B) receptor on megakaryocytes, and promotes their proliferation and differentiation. In the late stage, 5-HT may involve in the platelet release procedure by inducing nitric oxide (NO) synthesis via 5-HT(2A) receptors. 5-HT can also antagonize the apoptotic effect induced by thrombospondin-1 (TSP-1) which is a platelet alpha granule protein and has synergic effect with platelet-derived growth factor (PDGF) to enhance megakaryocytes proliferation. Therefore, 5-HT is likely to be an important substance in the feedback regulation of thrombopoiesis. In this review the 5-HT and its receptors, 5-HT as cell growth factor, pathway of 5-HT stimulating cell proliferation and influance of 5-HT on MK-progenitor cells were summarized.
Humans ; Megakaryocytes ; physiology ; Receptors, Serotonin ; metabolism ; Receptors, Serotonin, 5-HT2 ; metabolism ; Serotonin ; metabolism ; pharmacology ; Thrombopoiesis ; physiology ; Thrombopoietin ; physiology

To clarify the thrombopoietin (TPO) production in patients with end-stage liver cirrhosis and uremia under hemodialysis, plasma TPO levels in patients with liver cirrhosis (n = 15), uremia under hemodialysis (n = 20) and healthy controls (n = 40) were measured by using a sandwich enzyme linked immunosorbent assay. Relationship between megakaryocytopoiesis and plasma TPO levels was analysed by linear regression. The results showed that the mean plasma TPO concentration in the uremic patients was significantly lower than that in the healthy volunteers, whereas plasma TPO level in end-stage liver cirrhosis was not significantly different from that of normal controls; plasma TPO levels in liver cirrhosis and uremic patients did not significantly influence megakaryocytopoiesis. It is concluded that end-stage liver cirrhosis patients maintained normal plasma TPO levels, but the production of TPO was significantly reduced in renal failure patients. Thrombocytopenia in liver cirrhosis appears to be not related to plasma TPO levels.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Liver Cirrhosis ; blood ; Male ; Middle Aged ; Thrombopoiesis ; Thrombopoietin ; blood ; Uremia ; blood