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

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*

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*

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

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

A 12-year-old boy developed pure red cell anemia(PRCA) during a combination therapy of antiepileptic drugs(AEDs) for epilepsy. His complex partial seizure was intractable to monotherapy. During 7 months of treatment, he was treated with Vigabatrin, Carbamazepine and Valproate. While switching from Carbamazepine to Valproate, he presented anemia but with no jaundice. His hemoglobin was 4.1g/dl bone-marrow biopsy revealed erythroid hypoplasia with normal myelopoiesis and megakaryocytopoiesis, indicating PRCA. Rapid recovery from PRCA was observed 1 month after discontinuation of Valproate, without immunosuppressive therapy. Although the hematologic toxicity of AEDs is well documented, isolated cessation of red cell production is uncommon. Our observation suggests that the synergistic toxicity caused by Valproate and Carbamazepine may induce PRCA through the inhibitory effect beyond the differentiation stage of BFU-E and CFU-E.
Anemia* ; Anticonvulsants* ; Biopsy ; Carbamazepine ; Child ; Epilepsy ; Erythroid Precursor Cells ; Humans ; Jaundice ; Male ; Myelopoiesis ; Seizures ; Thrombopoiesis ; Valproic Acid ; Vigabatrin

BACKGROUND: The clinical significance of mean platelet volume (MPV), platelet distribution width (PDW) and megathrombocyte index (MTI) is not clear. METHODS: We examined platelet indices in 900 cases of patients with hematologic disorders and compared them with those of the control to predict thrombopoiesis in the bone marrow. MPV and PDW were measured by Coulter Counter STKS (U.S.A). We calculated megathrombocyte index (MTI, the percentage of megathrombocytes) in the peripheral blood film using ocular micrometer, and examined megakaryocyte number in the bone marrow aspirates. RESULTS: In patients with acute leukemia, and aplastic anemia, MPV and MTI were lower than the control but PDW was higher. In myeloproliferative disorders, all platelet indices were higher, and in ITP (idiopathic thrombocytopenic purpura), MPV and MTI were higher but PDW was not significantly different. MTI was higher in complete remission than initial acute leukemia. All platelet indices were not significantly different between pre- and post-BMT in AML. But in aplastic anemia, MPV and MTI were higher in post-BMT than pre-BMT. MTI was a better index to screen than MPV in the decreased megakaryocyte group, but in increased megakaryocyte group, there was no difference in screening ability between MPV and MTI. CONCLUSIONS: The platelet indices in peripheral blood may be good markers for predicting thrombopoiesis in hematologic disorders and in post chemotherapy of acute leukemia. In addition, after BMT of aplastic anemia, these indices could be used as valuable markers of engraftment.
Anemia, Aplastic ; Blood Platelets* ; Bone Marrow ; Drug Therapy ; Humans ; Leukemia ; Mass Screening ; Mean Platelet Volume ; Megakaryocytes ; Myeloproliferative Disorders ; Thrombopoiesis

BACKGROUND: It has been known that the increase of reticulated platelets indicates the increase of thrombopoiesis in platelet consumptive diseases or the impending platelet recovery in patients with thrombocytopenic conditions. A new rapid automated method to assess reticulated platelets, the immature platelet fraction (IPF), was recently introduced. We evaluated the usefulness of the IPF for the prediction of platelet recovery in patients after hematopoietic stem cell transplantation (HSCT) and cytotoxic chemotherapy. METHODS: Thirty one healthy volunteers and 59 patients formed 3 groups: the allogenic HSCT group (n=23, an ABO major-mismatch 6 of 23), the autologous HSCT group (n=8) and the cytotoxic chemotherapy group (n=28). The platelet count, % of IPF and the % of reticulocytes were checked every day by using a Sysmex XE-2100. RESULTS: The IPF in the healthy volunteers was a mean of 2.2+/-1.6% (range: 0.3~6.7%), and the maximum level of the IPF in the patient group was 6.1+/-1.7% (range: 3.3~13.5%). The ideal cut-off value of the IPF increase to discriminate the platelet recovery group was 5.1%. When this cut-off value is used, the positive predictive value is 90.9% in the HSCT groups and 87.5% for the total patients. The 4 patients who showed an IPF higher than 5.1% without platelet recovery were in platelet consumptive conditions. It took 8.0+/-8.3 days to show platelet recovery after elevation of the IPF over 5.1% and an ABO major mismatch HSCT doesnt affect platelet recovery. CONCLUSION: The IPF is thought to be a useful parameter for the prediction of platelet recovery after HSCT and cytotoxic chemotherapy, but the problem of the patient' conditions affects the accuracy of the IPF, and the variable intervals between the increase of the IPF and platelet recovery is thought to be improved.
Blood Platelets* ; Drug Therapy ; Healthy Volunteers ; Hematopoietic Stem Cell Transplantation ; Humans ; Platelet Count ; Platelet Transfusion* ; Reticulocytes ; Thrombopoiesis