Recent Advances in SARS-CoV-2-Induced Immune Thrombocytopenia --Review / 中国实验血液学杂志

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.

Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness.@*METHODS@#Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected.@*RESULTS@#Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01).@*CONCLUSION@#The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.

Effect of Recombinant Human Thrombopoietin (rhTPO) on Hematopoietic Reconstitution in Allogeneic Hematopoietic Stem Cell Transplantation Model / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of recombinant human thrombopoietin (rhTPO) on hematopoietic reconstruction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) model.@*METHODS@#The C57BL/6 mice were employed as the donors, and BALB/c mice as recipients. The bone marrow mononuclear cells of the donor mice were extracted and pretreated, which then were injected with 5×106 per mouse through the tail vein of the recipient to establish an allo-HSCT model. The implantation of hematopoietic stem cells in the recipient mice was detected by flow cytometry on the 28th day after transplantation. Next, the successfully modeled recipient mice were randomly divided into experimental group and control group. The rhTPO was injected into mice in the experimental group on the first day after transplantation, while the saline was injected into mice in the control group. Both groups were injected for 14 consecutive days. The peripheral blood and bone marrow hematopoiesis of the two groups were observed on day 1, 3, 7, 14, and 21 after transplantation.@*RESULTS@#The expression rate of H-2Kb in the bone marrow of recipient mice was 43.85% (>20%) on the 28th day after transplantation, which indicated that the recipient mice were successfully chimerized. Meanwhile, counts of PLTs on the day 3, 7, 14, and 21 after transplantation in the experimental group were higher than those in the control group with statistical significances (P<0.05). In addition, hematopoietic function of bone marrow was suppressed in both groups on day 1, 3 and 7 after transplantation, but hematopoietic bone marrow hyperplasia was better in the experimental group than in the control group. On day 14 and 21 after transplantation, the hematopoietic function of bone marrow in the two groups was recovered, and the experimental group showed more obvious than the control group.@*CONCLUSION@#rhTPO can effectively stimulate the production of PLTs and facilitate the recovery of white blood cells and hemoglobin after allo-HSCT, and promote hematopoietic recovery and reconstitution of bone marrow.

Effect of artificial liver with double plasma molecular absorb system model on patients' platelets and corresponding treatment strategy / 北京大学学报(医学版)

OBJECTIVE@#To compare the effects of artificial liver treatment with double plasma molecular adsorption system(DPMAS) mode and traditional plasma exchange (PE) mode on platelets in patients, and to evaluate the clinical efficacy of recombinent human thrombopoietin (rhTPO) in the treatment of thrombocytopenia.@*METHODS@#A total of fifteen patients undergoing artificial liver with DPMAS model admitted to the Fifth Affiliated Hospital of Guangzhou Medical University from January 2018 to November 2020 were selected and included in the DPMAS group, and another 15 patients receiving PE were selected and included in the PE group. The improvement of clinical symptoms, such as fatigue, jaundice, oliguria, edema, etc. before and after artificial liver treatment was compared between the two groups, and the trend of blood routine (especially platelet), coagulation function and other indexes before and after treatment were compared between the two groups. The use of rhTPO and the number of platelets were recorded during treatment.@*RESULTS@#The improvement rate of clinical symptoms in DPMAS group was 86.67%, which was higher than that in PE group, but the difference was not statistically significant (P>0.05). There was no statistical significance in the outcome of the two groups within 90 days (P>0.05). There was no significant difference in white blood cell (WBC) and hemoglobin (HB) between the two groups after treatment (P>0.05). However, the level of platelet(PLT) in DPMAS group was significantly lower than that before treatment (P < 0.05), and was significantly lower than that in PE group (P < 0.05). After treatment, the international normalized ratio (INR) level in PE group was significantly improved (P < 0.05), but there was no significant difference in the INR level in DPMAS group (P>0.05). The patients in the DPMAS group received an average of (8.2±3.1) doses of rhTPO and (1.5±0.3) IU of platelet transfusions during hospitalization. In DMPAS group, platelets increased significantly after infusion of terbium.@*CONCLUSION@#Compared with PE mode, the artificial liver with DPMAS mode can reduce platelet levels in patients, but the application of rhTPO can stimulate platelet regeneration and increase platelet levels in the patients, thereby reducing the risk of bleeding due to platelet hypoplasia.

The Treatment of Newly Diagnosed Primary Immune Thrombocytopenia by Recombinant Human Thrombopoietin Combined with Glucocorticoid / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP).@*METHODS@#Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed.@*RESULTS@#The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment.@*CONCLUSION@#RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.

Effect of rhTPO and rhIL-11 on Thrombocytopenia after Chemotherapy in Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze and compare the efficacy of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of thrombocytopenia after chemotherapy in acute leukemia patients.@*METHODS@#180 patients with acute leukemia complicated with thrombocytopenia after chemotherapy in the First Affiliated Hospital of Anhui Medical University were analyzed retrospectively. Among them, 50 patients who treated with rhTPO and did not receive platelet transfusion were set as group A, 50 patients treated with rhTPO and receive platelet transfusion were set as group B, Forty patients treated with rhIL-11 without platelet transfusion were set as group C, Forty patients who treated with rhIL-11 and received platelet transfusion were set as group D. The duration of PLT below 20×109/L, the days it takes for PLT to recover to more than 100×109/L, and the incidence of different bleeding degrees were compared among several groups.@*RESULTS@#The duration of PLT<20×109/L in group A(3.72±1.14 d) was significantly shorter than that in group C(4.93±1.33 d) (P<0.001), and there was no significant difference from group B (P>0.05). The duration of PLT<20×109/L in group B(3.06±0.91 d) was significantly shorter than that in group D(4.65±0.98 d) (P<0.001), while the difference in duration of days between group C and D was not statistically significant (P>0.05). The times for PLT to recover to 100×109/L in group A(13.46±1.67 d) were significantly shorter than that in group C(16.85±2.13 d) (P<0.05), but there was no significant difference from group B (P>0.05). The time required for PLT to recover to 100×109/L in group B(13.36±1.49 d) were significantly shorter than that in group D(16.18±1.78 d) (P<0.05), while the difference in the days required for group C and group D was not statistically significant (P>0.05). The incidence of high bleeding risk in group B was significantly lower than that in group A (22% vs 44%, P<0.05), the incidence of high bleeding risk in group D was significantly lower than that in group C (32% vs 65%, P<0.05), and the incidence of high bleeding risk in group A was significantly lower than that in group C (44% vs 65%, P<0.05). The incidence of high bleeding risk in group B(22%) was lower than that in group D(32.5%), and the difference was not statistically significant (P>0.05).@*CONCLUSION@#In the treatment of acute leukemia patients with thrombocytopenia after chemotherapy, compared with rhIL-11, rhTPO can significantly shorten the duration for patients in a status with extremely low levels of PLT and the recovery time of PLT to normal range. In addition, PLT transfusion cannot speed up the time for patients to raise platelets to a safe range, nor can it shorten the duration of low PLT levels, but it can reduce the incidence of high bleeding risk events.

Trombocitopenia imune associada à COVID-19: relato de caso e revisão de literatura / Immune thrombocytopenia associated to Covid-19: case report and literature review

Pacientes com COVID-19 podem apresentar trombocitopenia grave. Esse achado tem importante impacto no aumento de desfechos negativos e mortalidade, representando um importante fator prognóstico da doença. Vários mecanismos etiopatogênicos foram descritos, sendo a trombocitopenia imune um dos fatores mais frequentes. A abordagem terapêutica inclui como opções: corticoterapia, imunoglobulina, transfusão de plaquetas e análogos da trombopoietina. Este estudo tem como objetivo apresentar o relato de caso de uma paciente com PCR positivo para SARS-CoV-2, que desenvolveu queda acentuada e abrupta das plaquetas no 20º dia de internação. Além disso, casos semelhantes na literatura foram analisados e as possibilidades terapêuticas elencadas. Por fim, conclui-se que há a necessidade de estudos mais amplos para auxiliar a criação de protocolos sistematizados para o diagnóstico e abordagem dessa condição.

COVID-19 patients may experience severe thrombocytopenia. Such finding has an important impact on the increase in negative outcomes and mortality, representing an important prognostic factor of the disease. Several etiopathogenetic mechanisms have been described, in which immune thrombocytopenia is one of the most frequent. The therapeutic approach includes as options: corticosteroid therapy, immunoglobulin, platelet transfusion and thrombopoietin analogs. The following study aims to present a case report of a patient with positive PCR for SARSCoV-2 who developed a severe and abrupt drop in platelets on the 20th day of hospitalization. In addition, similar cases reports in the literature were analyzed and the therapeutic possibilities were listed. Finally, it is concluded that there is a need for broader studies to help create systematic protocols for the diagnosis and approach of this condition.

Research Status of TPO/c-MPL Signaling Pathway in Acute Myeloid Leukemia--Review / 中国实验血液学杂志

Thrombopoietin (TPO) can activate hematopoietic cell proliferation by its receptor c-MPL mediated downstream pathways and induce the generation of megakaryocyte. In recent years, domestic and foreign researches have confirmed that TPO/ c-MPL pathway also plays an important role in the self-renewal and quiescence of leukemia stem cell, and its expression in acute myeloid leukemia (AML) also indicates the chemotherapy resistance and poor prognosis. In this article, the research progress of the roles of TPO/c-MPL pathway in chemotherapy resistance, prognosis of AML patients, and the application of TPO/ c-MPL receptor agonists in AML were summarized briefly.

Effect of rhTPO to the Proliferation and Apoptosis of Acute Myeloid Leukemia Cell Lines / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of recombinant human thrombopoietin (rhTPO) to proliferation and apoptosis of acute myeloid leukemia (AML) cell lines.@*METHODS@#After the treatment of different concentrations of rhTPO (0, 50, 100 ng/ml) for different time (24,48,72 h)，the cell proliferation rates of the AML cell lines (Kasumi-1, Skno-1, HEL, HL-60, THP-1) were determined by CCK-8 method. Apoptosis rate of each cell line cocultured with rhTPO was detected by Annexin V/PI method. The relative expression of TPO receptor c-MPL (myeloproliferative clonal antibody) mRNA in AML cell lines was detected by Q-PCR. The expression of c-MPL protein in each cell line was detected by Western blot. The expression of c-MPL antigen in HL-60 cells treated by different concentrations of rhTPO was detected by Flow cytometry.@*RESULTS@#RhTPO showed no promotion to the proliferation of Kasumi-1, Skno-1, HEL, HL-60, THP-1 cell lines，however，it showed inhibitory effect to cell proliferation (72 h 0 ng/ml vs 100 ng/ml, P= 0.029) and pro-apoptotic (48 h 0 ng/ml vs 50 ng/ml, P=0.0143) in HL-60 cells. In Kasumi-1, Skno-1, HEL and THP-1 cells, there showed no statistically significant differences in apoptosis rate among each groups treated by different concentrations of rhTPO. Each AML cell line showed different levels of c-MPL gene and c-MPL protein expression, but HEL cells showed the highest expression in both of them. After HL-60 cells were treated by different concentrations of rhTPO for 48 hours, there showed no statistical difference in c-MPL antigen expression among each groups.@*CONCLUSION@#RhTPO can not promote the proliferation of Kasumi-1, Skno-1, HEL, HL-60 and THP-1 leukemia cell lines. On the contrary, rhTPO can inhibit HL-60 cell proliferation and promote its apoptosis, and this effect is not related to c-MPL gene expression or protein expression.

Thrombopoietin is associated with a prognosis of gastric adenocarcinoma

SUMMARY OBJECTIVE Thrombopoietin (THPO) is well-known as a megakaryocyte growth and development factor (MGDF) involved in megakaryocyte proliferation and maturation. To explore the biological effects of THPO in gastric adenocarcinoma, we conducted this study. Methods: By accessing the TCGA database, the expression level of THPO was determined in tumor tissues. The association between THPO expression and clinical features, or prognostic significance was described by Cox regression analysis and Kaplan-Meier. The SiRNA method was used to decline the THPO expression; then cell viability, invasion, and migration were detected to verify the effects of the knockdown of THPO. qPCR and western blotting were implemented to examine the expression level of THPO. Results: The expression of THPO was increased in tumor tissue and cells, its high-regulation was associated with a poor prognosis in patients with gastric adenocarcinoma. Cell viability, invasion, and migration were suppressed in AGS with the down-regulation of THPO. Furthermore, on the basis of si-THPO transfection, E-cadherin was promoted while N-cadherin and Vimentin were attenuated. CONCLUSION Our results revealed that THPO may be a potent marker of gastric adenocarcinoma, providing a novel potential screening method for gastric adenocarcinoma.

RESUMO OBJETIVO Trombopoetina (THPO) é um conhecido fator de desenvolvimento e crescimento megacariócito (MGDF) envolvido na proliferação e maturação de megacariócitos. Realizamos este estudo para explorar os efeitos biológicos do THPO no adenocarcinoma gástrico. Metodologia: O nível de expressão do THPO em tecidos tumorais foi determinado acessando a banco de dados TCGA. A associação entre a expressão de THPO e características clínicas ou relevância no prognóstico foi descrita através da análise de Kaplan-Meier e regressão de Cox. O método SiRNA foi utilizado para reduzir a expressão da THPO e, em seguida, a viabilidade, invasão, e migração celular foram detectadas para verificar os efeitos da redução do THPO. qPCR e western blotting foram utilizados para examinar o nível de expressão do THPO. Resultados: A expressão do THPO estava aumentada em tecido e células tumorais, esse aumento estava associado com um prognóstico negativo para pacientes com adenocarcinoma gástrico. A invasão e migração celular foram suprimidos em AGS com a redução do THPO. Além disso, com base na transfecção de si-THPO, a E-caderina foi promovida, enquanto a N-caderina e Vimentina foram atenuadas. Conclusão nossos resultados demonstram que o thpo pode ser um potente marcador de adenocarcinoma gástrico, com potencial para ser um novo tipo de triagem para adenocarcinoma gástrico.

Methodology of Differentiation of Bone Marrow Cells into Megakaryocytes in Vitro / 中国实验血液学杂志

OBJECTIVE@#To explore the method for inducing the differentiation of bone marrow cells into megakaryocytes in vitro so as to use for evaluating the activity of traditional Chinese medicines.@*METHODS@#The bone marrow cells were separated from femurs and tibias of mice. The experiments were divided into 4 groups: control (no adding cytokines), TPO (adding 50 ng/ml TPO), TPO+SCF (50 ng/ml+50 ng/ml) and TPO+SCF+IL-6+IL-9 (50 ng/ml+50 ng/ml+20 ng/ml+20 ng/ml). The bone marrow cells in 4 groups were cultured in vitro for 6 d. Then the cell growth status was observed by the inverted microscopy, and the cell count was detected by using the automatic cell counter. The ratio and absolute count of megakaryocytes were detected by flow cytometry.@*RESULTS@#Compared with control, three induction methods could stimulate the differentiation of bone marrow cells into megakaryocytes in vitro. TPO could slightly enhance the differentiation of bone marrow cells into megakaryocytes. Both the combination of TPO and SCF, and the combination of TPO, SCF, IL-6 and IL-9 could intensively stimulate proliferation of bone morrow cells and promote the differentiation of bone marrow cells into megakaryocytes. The addition of IL-6 and IL-9 could decrease the proliferation of non-megakaryocytes, but promote the differentiation of bone marrow cells into megakaryocytes.@*CONCLUSION@#The optimized differentiation of bone marrow cells into megakaryocytes has been completed by co-induction regimen of TPO, SCF, IL-6 and IL-9, which can be used to screen and evaluate traditional Chinese medicines promoting formation of platelets.

Thrombopoietin promotes megakaryopoiesis protecting bone marrow endothelial function in patients undergoing chemotherapy for hematological malignancies / 南方医科大学学报

OBJECTIVE@#To explore whether thrombopoietin (TPO) can rescue megakaryopoiesis by protecting bone marrowderived endothelial progenitor cells (BM-EPCs) in patients receiving chemotherapy for hematological malignancies.@*METHODS@#Bone marrow samples were collected from 23 patients with hematological malignancies 30 days after chemotherapy and from 10 healthy volunteers. BM-EPCs isolated from the samples were identified by staining for CD34, CD309 and CD133, and their proliferation in response to treatment with TPO was assessed using CCK8 assay. DiL-Ac-LDL uptake and FITC-UEA-I binding assay were performed to evaluate the amount of BM-EPCs from the subjects. Tube-formation and migration experiments were used for functional assessment of the BM-EPCs. The BM-EPCs with or without TPO treatment were co-cultured with human megakaryocytes, and the proliferation of the megakaryocytes was detected with flow cytometry.@*RESULTS@#Flow cytometry indicated that the TPO-treated cells had high expressions of CD34, CD133, and CD309. CCK8 assay demonstrated that TPO treatment enhanced the proliferation of the BM-EPCs, and the optimal concentration of TPO was 100 μg/L. Double immunofluorescence assay indicated that the number of BM-EPC was significantly higher in TPO-treated group than in the control group. The TPO-treated BM-EPCs exhibited stronger tube-formation and migration abilities ( < 0.05) and more significantly enhanced the proliferation of co-cultured human megakaryocytes than the control cells ( < 0.05).@*CONCLUSIONS@#TPO can directly stimulate megakaryopoiesis and reduce hemorrhage via protecting the function of BM-EPCs in patients following chemotherapy for hematological malignancies.

Megacariopoyesis humana in vitro: determinación de la concentración óptima de trombopoyetina / In vitro human megacaryocytopoiesis: determination of thrombopoietin optimal concentration / Megacariópoiesis humana in vitro: determinação da concentração ótima da trombopoietina

El estudio de la megacariopoyesis humana se ha visto obstaculizado por la relativa escasez de megacariocitos en la médula ósea (0,05-0,2 % de las células medulares), lo que ha llevado a la optimización de protocolos de expansión in vitro a partir de precursores de diversos orígenes (cordón umbilical, médula ósea y sangre periférica con o sin movilización previa). Los cultivos celulares a partir de precursores han permitido la producción y el estudio tanto de megacariocitos así como de proplaquetas y plaquetas Sin embargo, la producción in vitro óptima de megacariocitos que culminen todos los estadios de diferenciación es un reto aún no resuelto. En este trabajo reportamos los hallazgos concernientes a la determinación de las condiciones y concentraciones de trombopoyetina para lograr una óptima relación entre la cantidad de trombopoyetina empleada y el porcentaje y grado de diferenciación megacariocítica en muestras obtenidas de cinco donantes alogénicos aceptados para trasplante de médula ósea.

The study of human megakaryocytopoiesis has been hampered by the relative scarcity of megakaryocytes in bone marrow (0.05-0.2 % of medullary cells), which has led to the optimization of protocols of in vitro expansion of precursors from diverse sources (umbilical cord, bone marrow and peripheral blood with or without previous mobilization). Cell cultures from different precursors have allowed the production and study of megakaryocytes as well as proplatelets and platelets. However, the in vitro production of megakaryocytes that culminate all stages of differentiation is a challenge that has not yet been resolved. In this work we report the findings related to the determination of thrombopoietin treatment conditions and concentrations to achieve an optimal relationship between the amount of thrombopoietin and the percentage and degree of megakaryocytic differentiation in five allogeneic donors that were accepted for bone marrow transplantation.

O estudo da megacariopoiese humana tem sido dificultado pela relativa escassez de megacariócitos na medula óssea (0,05-0,2 % das células medulares), o que levou à otimização dos protocolos de expansão in vitro a partir de precursores de diversas origens (cordão umbilical, medula óssea e sangue periférico com ou sem mobilização prévia). Culturas de células a partir de precursores permitiram a produção e o estudo tanto de megacariócitos e de proplaquetas e plaquetas. No entanto, a produção ótima in vitro de megacariócitos que culminam em todas as fases de diferenciação é um desafio ainda não resolvido. Neste trabalho, relatamos as descobertas relativas à determinação das condições e concentrações de trombopoietina para obter uma relação ótima entre a quantidade de trombopoietina usada e a taxa e o grau de diferenciação megacariocítica em amostras obtidas de cinco doadores alogênicos aceitos para transplante de medula óssea.

Effects of Recombinant Human Thrombopoietin on Funtion of T and B Lymphocyte in Prieary ITP Patients / 中国实验血液学杂志

OBJECTIVE@#To study the changes of Th1 and Th2 type cytokines and B lymphocyte level and their clinical significance in idiopathic thrombocytopenic purpura (ITP) patients treated by recombinant human thrombopoietin (rhTPO).@*METHODS@#The peripheral blood levels of Th1 and Th2 type of cytokines and B lymphocyte were estimated by CBA in 48 patients with ITP, and compared with those in 35 control persons of heath examination.@*RESULTS@#Before treatment, the levels of Th1 type cytokines and B lymphocyte in 48 patients with ITP were higher, and the levels of Th2 type cytokines were lower than those of healthy controls (P＜0.05). The levels of the peripheral blood CD19 cells, CD5CD19 cells, IL-2 expression negatively correlated with Plt counts in ITP patients (P＜0.05), the levels of IL-4 positively correlated with Plt counts (P＜0.05). After treatment with rhTPO, the levels of Th1 type cytokines and B lymphocytes in 48 patients with ITP significantly decreased, and the levels of Th2 type cytokines significantly increased in comparison with those before treatment (P＜0.05).@*CONCLUSION@#Peripheral blood Th1 and Th2 type cytokines express abnormally and level of B lymphocytes increases significantly in ITP patinets. The disease severity correlats with the levels of Th1 and Th2 type cytokines and B lymphocytes. Platelets increase after rhTPO treatment, showing that rhTPO can play an important role in regulating Th1 and Th2 immunologic balance and B lymphocyte level in ITP patients.

Tocilizumab-induced Thrombocytopenia in Patients with Rheumatoid Arthritis

OBJECTIVE: Interlukin-6 (IL-6) increases platelet count during inflammation and may act in a manner similar to thrombopoietin. Tocilizumab is a monoclonal antibody of the IL-6 receptor and widely used in the treatment of rheumatoid arthritis (RA). Here, we evaluated the incidence of tocilizumab-induced thrombocytopenia and clinical factors associated with the development of thrombocytopenia. METHODS: Patients with RA, who were treated with tocilizumab and had exposed to other biologics previously in a tertiary hospital between January 2014 and December 2017, were retrospectively evaluated. We compared occurrence of thrombocytopenia between tocilizumab and previous biologics. Furthermore, the factors associated with thrombocytopenia were analyzed using logistic regression analysis. RESULTS: In total, 114 patients with RA were treated with tocilizumab for mean 90.5 weeks (interquartile range, 30.9~174.9). Thrombocytopenia was reported in 14 patients (12.3%) and it was higher rate compared with previous biologics. Most cases were grade 1 thrombocytopenia. Multivariate analysis showed that patient age (odds ratio [OR], 2.170; 95% confidence interval [CI], 1.118~4.211; p=0.022) and platelet count prior to treatment with tocilizumab (OR, 0.972; 95% CI, 0.954~0.990; p=0.002) were significantly associated with the development of thrombocytopenia. CONCLUSION: Old age is risk factor for developing tocilizumab-induced thrombocytopenia and higher platelet count prior to treatment is associated with lowering risk of development of thrombocytopenia. However, thrombocytopenia was tolerable.

Curative Effect of Simply Hormone and Combined Gamma Globulin and Thrombopoietin on Primary Immune Thrombocytopenia / 中国实验血液学杂志

OBJECTIVE@#To investigate the curative effect of simply hormone and combined gamma globulin and thrombopoietin(TPO) on primary immune thrombocytopenia(PITP).@*METHODS@#100 patients with PITP were divided into simply drug groups, and combined drug group each for 50 cases. The patients in single drug group were given simply hormone therapy, the patients in combined drug group were given gamma globulin and thrombopoietin. The levels of TPO, platelet activating factor (PAF) were detected by DAS-ELISA. The differences of clinical curative effect, clinical indicators, biochemical indexes and adverse reactions between the two groups were compared.@*RESULTS@#The total effective rate of combined drug group (90.00%) was obviously higher than that in single drug group (66.00%)(P0.05), however, the above-mentioned indexes of two groups after treatment were lower than those before treatment (P0.05), the recurrence rate in combined drug group(2%) was obviously lower than that in single group(14.00%) (P<0.05).@*CONCLUSION@#The curative effect of hormone, as well as gamma globulin combined with TPO to treat PITP are satisfying, can obviously improve the levels of TPO, PAF, and the drug safety is higher. but the efficacy of combined drug is surperior to single drug.

THPO gene variants in patients with acquired aplastic anemia

ABSTRACT Background: Human aplastic anemia is a hematologic disease characterized by low peripheral blood cell counts associated with reduced numbers of hematopoietic stem and progenitor cells and a hypocellular bone marrow. Thrombopoietin (THPO) regulates megakaryocytes, but it also stimulates hematopoietic stem and progenitor cells. Biallelic mutations in the THPO gene have been reported in a family with recessive inherited aplastic anemia. Methods: This study screened 83 patients diagnosed with acquired aplastic anemia and 92 paired healthy controls for germline variants in the THPO gene using Sanger sequencing. Results: Three common single nucleotide polymorphisms were identified in patients and controls at comparable allele frequencies. There was no correlation between the single nucleotide polymorphism carrier status and platelet counts at diagnosis. Conclusion: The presence of THPO polymorphisms is comparable between patients with acquired aplastic anemia and healthy individuals.

Consensus on clinical diagnosis, treatment and prevention management of chemotherapy induced thrombocytopenia in China(2018) / 中华肿瘤杂志

Chemotherapy induced thrombocytopenia (CIT) is a common side-effect of chemotherapy in cancer patients, which lead to dose and cycle reduction or chemotherapy delay, or even the need of platelet transfusion. Therefore, CIT significantly increases the cost of treatment, reduces the efficacy of chemotherapy and the quality of life, and shortens the survival time of patients. The main treatments of CIT include transfusion of platelets, recombinant human thrombopoietin (rhTPO), and recombinant human interleukin-11 (rhIL-11). RhIL-11 is the first approved thrombocytopoietic cytokine. Interleukin-11 has been shown to be effective in the treatment of thrombocytopenia. RhTPO is a recombinant full-length glycosylated thrombopoietin, which is a ligand for c-Mpl protein. Several observations indicated that administration of rhTPO before and after chemotherapy might be beneficial to patients, which enhances platelet recovery and reduces thrombocytopenia after moderately myelosuppressive regimens. In recent years, the application of rhTPO in CIT treatment has dramatically changed the management and treatment plan of CIT. The China Society of Clinical Oncology (CSCO) published a consensus on CIT in 2014. Based on this, the expert committee updated "Consensus on clinical diagnosis, treatment and prevention management of chemotherapy induced thrombocytopenia in China (2018)" according to the recent literature and clinical research. The new evidence-based practice consensus for CIT aims to provide more reasonable diagnosis, treatment of prevention regimens for CIT patients to maintain the normal platelet counts.

Efficacy of recombinant human thrombopoietin combined with high-dose dexamethasone in the treatment of refractory immune thrombocytopenia in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with high-dose dexamethasone (DXM) in the treatment of children with refractory immune thrombocytopenic purpura (ITP).</p><p><b>METHODS</b>Fifty-eight ITP children who had failed first-line therapy were randomly divided into two groups: DXM treatment (n=27) and rhTPO + DXM treatment (n=31). The DXM treatment group received two continuous cycles of DXM treatment; in each cycle, patients received high-dose DXM (0.6 mg/kg daily) by intravenous drip for 4 days every 28 days. The rhTPO group received subcutaneous injection of rhTPO (300 U/kg daily) for 14 days additional to DXM treatment. The overall response rate (marked response rate + slight response rate) and adverse reactions were evaluated after 3, 7, and 14 days and 1, 2, and 3 months of treatment.</p><p><b>RESULTS</b>After 7 and 14 days and 1 month of treatment, the rhTPO + DXM treatment group had a significantly higher marked response rate and a significantly higher overall response rate than the DXM treatment group (P<0.05). After 2 months of treatment, the rhTPO + DXM treatment group had a significantly higher overall response rate than the DXM group (P<0.05). One patient in the DXM treatment group had liver damage during the first week of treatment. There was no hypertension, fever, rash, allergy, or weakness in the two groups.</p><p><b>CONCLUSIONS</b>rhTPO combined with high-dose DXM is an effective and safe approach for treating refractory ITP.</p>