Clinical observation of herombopag combined with recombinant human thrombopoietin in the treatment of primary immune thrombocytopenia / 中国药房

OBJECTIVE To investigate the clinical efficacy and safety of herombopag combined with recombinant human thrombopoietin （rhTPO） in the treatment of primary immune thrombocytopenia （ITP） in the real world. METHODS A retrospective study was conducted on the patients diagnosed with ITP in the Second Affiliated Hospital of Bengbu Medical College from January 2021 to December 2022. Among them， 98 patients who were treated with a combination of herombopag and rhTPO were included in the observation group， and 157 patients who were treated with rhTPO alone were included in the control group. The changes in platelet count， clinical efficacy， bleeding， platelet transfusion rate and adverse drug reactions before and after treatment were observed and compared between the two groups. RESULTS Since the 8th day of treatment， there was a statistically significant difference in platelet count between the two groups （[ 61.04±13.46）×109 L－1 in observation group， （52.11±12.06）× 109 L－1 in control group] （P＜0.05）， and there also was a statistically significant difference in the peak and stable values of platelet count between the two groups （P＜0.05）. The total effective rates of the observation group and the control group were 79.59% and 66.88%， with cumulative response rates of 81.32% and 68.68%， and median response durations of 8 days and 10 days， respectively； these differences were statistically significant （P＜0.05）. During the treatment period， the bleeding rates of the observation group and control group were 3.06% and 8.28% （P＜0.05）， bleeding events were categorized as grade 1 or 2， and platelet transfusion rates were 31.63% and 40.76%； the differences in bleeding rates and platelet transfusion rates between the two groups was statistically significant （P＜0.05）. The incidences of adverse drug reactions in the two groups were 11.22% and 9.55%， respectively， with no statistically significant difference （P＞0.05）， and no moderate to severe adverse drug reaction was found. CONCLUSIONS The combination of herombopag and rhTPO can significantly increase platelet levels and response rate， and reduce bleeding rate and platelet transfusion rate in ITP patients， with good safety.

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 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.

Clinical efficacy of avatrombopag combined with recombinant human thrombopoietin versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease / 中华消化外科杂志

Objective:To investigate the clinical efficacy of avatrombopag combined with recombinant human thrombopoietin (rhTPO) versus avatrombopag in the treatment of severe thrombocytopenia associated with chronic liver disease.Methods:The retrospective cohort study was conducted. The clinical data of 56 patients with severe thrombocytopenia associated with chronic liver disease who were admitted to the First Affiliated Hospital of University of Science and Technology of China from May 2020 to October 2021 were collected. There were 36 males and 20 females, aged from 33 to 74 years, with a median age of 54 years. Of 56 patients, 21 cases undergoing treatment of avatrombopag combined with rhTPO were allocated into the combined treatment group and 35 cases undergoing treatment of avatrombopag were allocated into the monotherapy group. Observation indicators: (1) changes of platelet after treatment; (2) adverse drug reaction. Follow-up was conducted using outpatient examination and telephone interview to detect changes of platelet and effects of treatment within 2 weeks after treatment. The follow-up was up to October 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and compari-son between groups was analyzed using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Changes of platelet after treatment. The platelet level within 1 to 5 days and 6 to 10 days after treatment in the combined treatment group were (35±19)×10 9/L and (73±41)×10 9/L, respectively. The above indicators of the monotherapy group were (40±30)×10 9/L and (70±51)×10 9/L, respectively. There was no significant difference in change trends of platelet before and after treatment between the two groups ( Fgroup=0.30, P>0.05). There was a significant difference in platelet count before and after treatment between the two groups ( Ftime=59.96, P<0.05). There was no interaction effect in change trends of platelet between the two groups ( Finteraction=0.40, P>0.05). The effective rates were 66.67%(14/21) in the combination therapy group and 54.29%(19/35) in the monotherapy group. There was no significant difference in the effective rate between the two groups ( χ2=0.83, P>0.05). (2) Adverse drug reaction. Cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria, fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea or peripheral tissue edema were 2, 4, 1, 2, 2, 7, 10, 6, 8, 14, 12, 5 in the combined treatment group, versus 5, 8, 1, 3, 5, 7, 19, 11,20, 19, 14, 5 in the monotherapy group, respectively. There was no significant difference in cases with headache, dizziness, blood transfusion reaction, hematuria, proteinuria between the two groups ( P>0.05), and there was no significant difference in cases with fever, abdominal pain, diarrhea, dyspepsia, fatigue, nausea, peripheral tissue edema between the two groups ( χ2=1.24, 0.23, 0.05, 1.91, 0.83, 2.04, 0.81, P>0.05). Conclusion:Both of avatrombopag combined with rhTPO and monotherapy of avatrom-bopag can be used to promote the platelet level in patients with severe thrombocytopenia associated with chronic liver disease, and avatrombopag combined with rhTPO does not provide better clinical benefits compared with monotherapy avatrombopag.

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.

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.

Cost-utility analysis of Recombinant human thrombopoietin injection and Etrapopa ethanolamine tablets in the second-line treatment of primary immune thrombocytopenia / 中国药房

OBJECTIVE To evaluate the econo mical efficiency of Recombinant human thrombopoietin injection （called “rhTPO”for short ）versus Etrapopa ethanolamine tablets （called“Etrapopa”for short ）in the second-line treatment of primary immune thrombocytopenia （ITP）in the Chinese adult patients. METHODS Based on the decision tree-embedded Markov model with a 4-week cycle ，the cost and utility related to bleeding events and adverse events after the use of the two drugs were measured and compared from the perspective of Chinese health system. The horizon was 12 weeks，and the cost and health outcome were not discounted. RESULTS Compared with Etrapopa ，rhTPO improved the quality adjusted life year by 0.002 5 and reduced the cost by 1 824.36 yuan，which was the absolute advantage scheme. Univariate sensitivity analysis showed that the base results were greatly affected by the dosage of rhTPO and Etrapopa during maintainance period. In most cases ，rhTPO was economical. Probability sensitivity analysis showed that when willingness-to-pay threshold varied between 0 yuan and 250 000 yuan，the probability about that rhTPO was economical ranges from 99.90％ to 100％. CONCLUSIONS Based on the available evidence ，rhTPO is more economical in the short term than Etrapopa in the second-line treatment of ITP.

Effect of recombinant human thrombopoietin on platelet activation and pyroptosis in mice with thrombocytopenia / 中华急诊医学杂志

Objective To study the effect and mechanism of recombinant human thrombopoietin (rhTPO) on platelet activation and pyroptosis in mice with lipopolysaccharide (LPS)-induced thrombocytopenia,and provide a theoretical basis for the clinical use of rhTPO.Methods One hundred C57BL/6 mice were randomly(random number) divided into 5 groups:blank control group (sham group),experimental control group (LPS group),low dose (L group,1.35 ×103U · kg-1 · d-1),medium dose (M group,2.7 ×103U · kg-1 · d-1),and high dose (H group,5.4 ×103U · kg-1 · d-1) rhTPO treatment groups.Continuous observation for 72 h.The positive expression rates of CD61/CD62p,Gasdermin D and Caspase-1 in washed platelets were detected by flow cytometry at 72 h,and the levels of IL-1β and IL-18 in plasma were detected by ELISA.Results Compared with the sham group,the survival rate of the LPS group was significantly lower (P＜ 0.01).Compared with the LPS group,the survival rates of the L,M and H groups were slightly increased,but the difference was not statistically significant (P＞0.05).There was no significant change in platelet count of the sham group before and after the experiment.The platelet count in the LPS group decreased significantly.The platelet count at 72 h in the L group was signiftcantly higher than those in the LPS,M and H groups (P＜0.01),and there was no significant difference between the M and H groups and LPS group (P＞0.05).Compared with the sham group,CD61/CD62p and Gasdermin-D protein expressions in the LPS group were significantly increased (P＜0.01),significantly decreased in the L group (P＜0.05),and not significantly changed in the M and H groups (P＞0.05).Caspase-1 expression was significantly increased in the LPS group compared with the sham group (P＜0.01),significantly decreased in the L and M groups compared with the LPS group (P＜0.05),and not significantly changed in the H group compared with the LPS group (P＞0.05).The levels ofplatelet-rich plasma IL-1 beta and IL-18 in the LPS group were significantly higher than those in the sham group (P＜0.01),while those in the L group were significantly lower than those in the LPS group (P＜0.01),and those in the M and H groups were not significantly changed than those in the LPS group (P＞0.05).Conclusions rhTPO can inhibit platelet activation and pyroptosis in LPS-induced thrombocytopenia mice,which provides basic research basis for the treatment of sepsis thrombocytopenia.

Effect of recombinant human thrombopoietin on endotoxin-induced thrombocytopenia in mice / 中华危重病急救医学

Objective@#To investigate the effect of recombinant human thrombopoietin (rhTPO) on thrombocytopenia (TCP) induced by endotoxin lipopolysaccharide (LPS) in mice.@*Methods@#Sixty male C57BL/6 mice were divided into normal saline (NS) control group (NS group), sepsis-induced TCP model group (LPS group) and rhTPO treatment group (LPS+rhTPO group) by random number table with 20 mice in each group. Sepsis-induced TCP model was reproduced by one intraperitoneal injection of LPS 30 mg/kg, and the mice in NS group were given the same amount of NS. In LPS+rhTPO group, 2.7 kU/kg rhTPO was subcutaneously injected into mice immediately after intraperitoneal injection of LPS, once every 24 hours. The mice in NS group and LPS group were injected subcutaneously with the same amount of NS. The observation period of each group lasted for 72 hours. The inner canthus blood was harvested before and every 24 hours after modeling, and the platelet count (PLT) was measured by animal blood cell counter. The eyeball blood of mice was harvested at 72 hours after modeling, and the proportion of CD61+CD62p+ cells in platelet-rich plasma was detected by flow cytometry, by which the platelet activation was reflected. Lung and spleen tissues of mice were harvested, and the positive expression of CD41 was determined by immunohistochemistry, by which the platelet sequestration in organs was reflected. Bone marrow cells from unilateral femur of mice were harvested, and the proportion of CD41+CD61+ cells was determined by flow cytometry to reflect the proliferation of bone marrow megakaryocytes.@*Results@#There was no significant difference in PLT among the groups before modeling. With the extension of the time after modeling, PLT in LPS group was decreased continuously, and increased slightly at 72 hours, but it was still significantly lower than that in NS group (×109/L: 308.60±21.70 vs. 1 152.72±50.27, P < 0.05); PLT in LPS+rhTPO group was increased continuously with the extension of modeling time, and it was significantly higher at 72 hours than that in LPS group (×109/L: 926.78±48.85 vs. 308.60±21.70, P < 0.05). At 72 hours after modeling, the proportion of CD61+CD62p+ cells in platelet-rich plasma of LPS group was significantly higher than that of NS group [(25.07±2.55)% vs. (4.17±0.38)%, P < 0.05], while the value in LPS+rhTPO group was significantly lower than that of LPS group [(15.92±1.26)% vs. (25.07±2.55)%, P < 0.05]. The proportion of CD41+CD61+ cells in bone marrow megakaryocytes of LPS group was significantly higher than that of NS group [(11.84±0.80)% vs. (3.60±0.42)%, P < 0.05], and the proportion of CD41+CD61+ cells in LPS+rhTPO group was significantly higher than that in LPS group [(30.96±2.49)% vs. (11.84±0.80)%, P < 0.05]. Immunohistochemistry showed that the positive expressions of CD41 in lung and spleen tissues of LPS group increased significantly than NS group [A value: 828.94±119.30 vs. 447.09±16.19 in lung tissue, (280.15±16.71)×103 vs. (0.65±0.26)×103 in spleen tissue, both P < 0.05], while the positive expressions of CD41 in lung and spleen tissues of LPS+rhTPO group decreased significantly than LPS group [A value: 542.78±2.95 vs. 828.94±119.30 in lung tissue, (129.40±13.49)×103 vs. (280.15±16.71)×103 in spleen tissue, both P < 0.05].@*Conclusion@#The rhTPO in endotoxin-induced TCP may stimulate the proliferation of bone marrow megakaryocytes, inhibit platelet activation and affect platelet sequestration in organs, so as to increase platelet levels.

Effect of recombinant human thrombopoietin on platelet activation and pyroptosis in mice with thrombocytopenia / 中华急诊医学杂志

Objective@#To study the effect and mechanism of recombinant human thrombopoietin (rhTPO) on platelet activation and pyroptosis in mice with lipopolysaccharide (LPS)- induced thrombocytopenia, and provide a theoretical basis for the clinical use of rhTPO.@*Methods@#One hundred C57BL/6 mice were randomly(random number) divided into 5 groups: blank control group (sham group), experimental control group (LPS group), low dose (L group, 1.35 ×103U·kg-1·d-1), medium dose (M group, 2.7 ×103U·kg-1·d-1), and high dose (H group, 5.4 ×103U·kg-1·d-1) rhTPO treatment groups. Continuous observation for 72 h. The positive expression rates of CD61/CD62p, Gasdermin D and Caspase-1 in washed platelets were detected by flow cytometry at 72 h, and the levels of IL-1β and IL-18 in plasma were detected by ELISA.@*Results@#Compared with the sham group, the survival rate of the LPS group was significantly lower (P< 0.01). Compared with the LPS group, the survival rates of the L, M and H groups were slightly increased, but the difference was not statistically significant (P>0.05). There was no significant change in platelet count of the sham group before and after the experiment. The platelet count in the LPS group decreased significantly. The platelet count at 72 h in the L group was significantly higher than those in the LPS, M and H groups (P<0.01), and there was no significant difference between the M and H groups and LPS group (P>0.05). Compared with the sham group, CD61/CD62p and Gasdermin-D protein expressions in the LPS group were significantly increased (P<0.01), significantly decreased in the L group (P<0.05), and not significantly changed in the M and H groups (P>0.05). Caspase-1 expression was significantly increased in the LPS group compared with the sham group (P<0.01), significantly decreased in the L and M groups compared with the LPS group (P<0.05), and not significantly changed in the H group compared with the LPS group (P>0.05). The levels of platelet-rich plasma IL-1 beta and IL-18 in the LPS group were significantly higher than those in the sham group (P<0.01), while those in the L group were significantly lower than those in the LPS group (P<0.01), and those in the M and H groups were not significantly changed than those in the LPS group (P>0.05).@*Conclusions@#rhTPO can inhibit platelet activation and pyroptosis in LPS-induced thrombocytopenia mice, which provides basic research basis for the treatment of sepsis thrombocytopenia.

Effect of recombinant human thrombopoietin on endotoxin-induced thrombocytopenia in mice / 中华危重病急救医学

Objective To investigate the effect of recombinant human thrombopoietin (rhTPO) on thrombocytopenia (TCP) induced by endotoxin lipopolysaccharide (LPS) in mice. Methods Sixty male C57BL/6 mice were divided into normal saline (NS) control group (NS group), sepsis-induced TCP model group (LPS group) and rhTPO treatment group (LPS+rhTPO group) by random number table with 20 mice in each group. Sepsis-induced TCP model was reproduced by one intraperitoneal injection of LPS 30 mg/kg, and the mice in NS group were given the same amount of NS. In LPS+rhTPO group, 2.7 kU/kg rhTPO was subcutaneously injected into mice immediately after intraperitoneal injection of LPS, once every 24 hours. The mice in NS group and LPS group were injected subcutaneously with the same amount of NS. The observation period of each group lasted for 72 hours. The inner canthus blood was harvested before and every 24 hours after modeling, and the platelet count (PLT) was measured by animal blood cell counter. The eyeball blood of mice was harvested at 72 hours after modeling, and the proportion of CD61+CD62p+ cells in platelet-rich plasma was detected by flow cytometry, by which the platelet activation was reflected. Lung and spleen tissues of mice were harvested, and the positive expression of CD41 was determined by immunohistochemistry, by which the platelet sequestration in organs was reflected. Bone marrow cells from unilateral femur of mice were harvested, and the proportion of CD41+CD61+ cells was determined by flow cytometry to reflect the proliferation of bone marrow megakaryocytes. Results There was no significant difference in PLT among the groups before modeling. With the extension of the time after modeling, PLT in LPS group was decreased continuously, and increased slightly at 72 hours, but it was still significantly lower than that in NS group (×109/L: 308.60±21.70 vs. 1 152.72±50.27, P < 0.05); PLT in LPS+rhTPO group was increased continuously with the extension of modeling time, and it was significantly higher at 72 hours than that in LPS group (×109/L: 926.78±48.85 vs. 308.60±21.70, P < 0.05). At 72 hours after modeling, the proportion of CD61+CD62p+ cells in platelet-rich plasma of LPS group was significantly higher than that of NS group [(25.07±2.55)% vs. (4.17±0.38)%, P < 0.05], while the value in LPS+rhTPO group was significantly lower than that of LPS group [(15.92±1.26)% vs. (25.07±2.55)%, P < 0.05]. The proportion of CD41+CD61+ cells in bone marrow megakaryocytes of LPS group was significantly higher than that of NS group [(11.84±0.80)% vs. (3.60±0.42)%, P < 0.05], and the proportion of CD41+CD61+ cells in LPS+rhTPO group was significantly higher than that in LPS group [(30.96±2.49)% vs. (11.84±0.80)%, P < 0.05]. Immunohistochemistry showed that the positive expressions of CD41 in lung and spleen tissues of LPS group increased significantly than NS group [A value: 828.94±119.30 vs. 447.09±16.19 in lung tissue, (280.15±16.71)×103 vs. (0.65±0.26)×103 in spleen tissue, both P < 0.05], while the positive expressions of CD41 in lung and spleen tissues of LPS+rhTPO group decreased significantly than LPS group [A value: 542.78±2.95 vs. 828.94±119.30 in lung tissue, (129.40±13.49)×103 vs. (280.15±16.71)×103 in spleen tissue, both P < 0.05]. Conclusion The rhTPO in endotoxin-induced TCP may stimulate the proliferation of bone marrow megakaryocytes, inhibit platelet activation and affect platelet sequestration in organs, so as to increase platelet levels.

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.

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.

A prospective study of the efficacy and safety of maintenance therapy with recombinant human thrombopoietin in patients with primary immune thrombocytopenia: a multicenter study / 中华血液学杂志

Objective@#To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO.@*Methods@#Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×109/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×109/L.@*Results@#A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×109/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×109/L) at 4th week, 8th week and 12th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×109/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild.@*Conclusion@#Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

The clinical efficacy of recombinant human thrombopoietin for the treatment of post-chemotherapy throm- bocytopenia of adult patients with acute myeloid leukemia / 实用医学杂志

Objective To study the effect of recombinant human thrombopoietin(rh TPO)for the treatment of post-chemotherapy thrombocytopenia in adult patients with acute myeloid leukemia(AML). Methods A total of 60 newly diagnesed AML patients ,law-and Intermediate-Rist with post-chemotherapy thrombocytopenia were randomly divided into experimental group (30 cases,rh TPO treatment)and control group(30 cases,no rhTPO treatment). Comparisons were made on the blood platelet recovery degree,the days of the blood platelet counting less than 20 × 109/L,the recovery days of the blood platelet counting more than 50 × 109/L,and incidence of adverse reac-tions of experimental group. Results After treatment,blood platelet recovery level between the experimental group and the control group has no difference(P>0.05). The days of the blood platelet counting less than 20 × 109/L and the recovery days of the blood platelet counting more than 50 × 109/L of experimental group were less than the control group separately(P < 0.05). The experimental group had low incidence of adverse reactions(6.7%). Conclusion rhTPO can not significantly increase the level of platelet recovery of AML patients after chemotherapy ,but can obvi-ously shorten the time of platelet recovery without obvious adverse reactions. The specific time needs further studied.

Efficacy and safety of recombinant human thrombopoietin combined with different doses of glucocorticoid on patients with thrombocytopenia / 中国医学装备

Objective:To analyze the efficacy and safety of recombinant human thrombopoietin combined with different doses of glucocorticoid on patients with thrombocytopenia.Methods: Choose patients with thrombocytopenia in our hospital as research subjects, randomly divided into control group with recombinant human thrombopoietin and normal glucocorticoid, observation group with recombinant human thrombopoietin and reduction glucocorticoid, compared platelet levels, onset time, coagulation and adverse reactions.Results: 1)observation group patients platelet levels after treatment was significantly higher than control group patients (t=5.931,t=6.273;P<0.05); 2)observation group patients average rise time of platelet were significantly less than control group patients (t=4.284,t=6.294, t=6.482;P<0.05); 3)observation group patients PT, APTT values were lower than control group, FIB level was higher (t=5.392,t=6.183,t=7.273;P<0.05); 4)patients in the observation group incidence of various types of adverse reactions after treatment was significantly lower than control group patients(x2=7.017,x2=4.833,x2=5.199,x2=4.921;P<0.05).Conclusion: The recombinant human thrombopoietin joint reduction of glucocorticoid therapy can improve platelet levels in patients with thrombocytopenia, improve coagulation and rapid onset of adverse reactions , with positive clinical significance.

Clinical observation on recombinant human thrombopoietin in the treatment of chemotherapy-induced thrombocytopenia in solid tumor patients / 中国癌症杂志

Background and purpose:Reduced peripheral blood platelet count is a common toxicity in patients with hematological malignancy after chemotherapy.The purpose of this study was to observe the eff icacy and safety of recombinant human thrombopoietin(rhTPO)in the treatment of thrombocytopenia induced by chemotherapy.Methods:A total of 25 patients with solid tumor,who developed thrombocytopenia induced by chemotherapy(PLT≤70?109/L) after the f irst cycle of chemotherapy(control group),was studied by self-cross control.6-24 h after the second cycle of chemotherapy(treatment group) with identical scheme of the f irst cycle chemotherapy,they were given subcutaneous injection of rhTPO 15 000 U/d for 7 to 14 consecutive days or until platelet count ≥100?109/L or the increasing count ≥50?109/L.Results:The mean platelet count of the patients after rhTPO treatment was higher at different time points of the treatment group than that of the control group.The minimal PLT count of the treatment group and the control group after chemotherapy were(80.3?39.30)?109/L and(34.7?21.2)?109/L(P0.05).The time of PLT count to recover was found to be more than 75?109/L and 100?109/L in treatment group after chemotherapy was(9.8?4.2)d and(12.8?3.6)d,compared to(19.1?4.5)d and(24.3?1.4)d(P