BACKGROUND Eltrombopag is an orally administered thrombopoietin receptor agonist linked to a heightened risk of treatment-related thromboembolism.Both venous and arterial thromboses have been documented in the medical...BACKGROUND Eltrombopag is an orally administered thrombopoietin receptor agonist linked to a heightened risk of treatment-related thromboembolism.Both venous and arterial thromboses have been documented in the medical literature.CASE SUMMARY In the absence of nephropathy,a 48-year-old patient receiving eltrombopag for immune thrombocytopenia(ITP)developed renal vein thrombosis and pulmonary embolism.The renal vein thrombus spontaneously resolved during subsequent anticoagulant treatment,restoring venous circulation.CONCLUSION A rapid upsurge in platelets,rather than their absolute number,may trigger thrombotic events in this setting.For patients at high thrombotic risk,individualized eltrombopag dosing and vigilance in platelet monitoring are perhaps needed during treatment of ITP.展开更多
Chronic hepatitis C is a public health problem worldwide.Unfortunately,not all patients may benefit from antiviral therapy due to thrombocytopenia.Its causes are represented by portal hypertension and platelet sequest...Chronic hepatitis C is a public health problem worldwide.Unfortunately,not all patients may benefit from antiviral therapy due to thrombocytopenia.Its causes are represented by portal hypertension and platelet sequestration in the spleen,decreased serum levels or activity of thrombopoietin,the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon.Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients.Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner.Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia.Its indication for other hemopathies or situations(like thrombocytopenia secondary to chemo- or radiotherapy,acute leukemia,myelodysplastic syndroms,acquired and hereditary bone marrow failure,and platelet donors) is under study.Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment.We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus,highlighting the benefits and mentioning possible adverse effects.In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery.Eltrombopag is a solution for many of these patients,which allows them receiving antiviral therapy and sometimes getting a sustained virological response,but they must be well monitored to prevent possible thromboembolic or bone marrow complications or liver failure occurrence.展开更多
Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder, defined by a platelet count of less than 100 × 109/L, secondary to impaired production and immune destruction of platelets. Bleeding tende...Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder, defined by a platelet count of less than 100 × 109/L, secondary to impaired production and immune destruction of platelets. Bleeding tendency is the main presentation of this condition. Clinical symptoms and investigations will confirm the diagnosis. Steroid is the first line of treatment. Although Rituximab and Thrombopoietin receptor agonists are useful second line agents in non-pregnant adults, the data about their role in pregnancy are still limited. We present the case of a 30 year old primigravida, who was a known case of chronic ITP since childhood;the course of her disease was fluctuating, for which oral steroids were used accordingly. She presented with gum bleeding and petechial rash with very low platelets count. She was sponsored by the Patient Support Program and was given Eltrombopag during the third trimester. She responded well to Eltrombopag with no noticeable side effects, neither to the mother nor to the baby so far. Eltrombopag has been assigned Category C by the Federal Drugs Agency (FDA) nevertheless there are no well controlled data in the literature about its role in pregnancy.展开更多
Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombin...Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombinant products was associated with formation of autoantibodies. Eltrombopag is an oral thrombopoietin agonist found effective in raising platelet counts in patients with immune thrombocytopenia. The drug has now been found to be useful in raising platelet counts in thrombocytopenia related to liver disease including cirrhosis and chronic viral hepatitis. Although the drug may help enable adequate interferon therapy in patients with HCV infection and help carry out invasive procedures in patients with cirrhosis, concerns have been raised of possible thrombotic complications including portal vein thrombosis. Randomized trials have shown that use of eltrombopag concomitant with pegylated interferon and ribavirin increased the chances of sustained virologic response while decreasing the dose reductions of interferon. The data on use of romiplostim in these clinical indications is also emerging. However, in the future, availability of interferon free regimens is likely to decrease the use of eltrombopag for enabling antiviral therapy. The review discusses the role of eltrombopag in management of liver disease related thrombocytopenia in wake of recent data as also the dosage, precautions and adverse effects associated with its use.展开更多
Importance:Eltrombopag has been recommended for pediatric immune thrombocytopenia(ITP).Response and adverse drug reactions(ADRs)varied widely between individuals,even at the same dose of eltrombopag.The appropriate el...Importance:Eltrombopag has been recommended for pediatric immune thrombocytopenia(ITP).Response and adverse drug reactions(ADRs)varied widely between individuals,even at the same dose of eltrombopag.The appropriate eltrombopag concentration in ITP has not been reported.Objective:This study aims to explore the appropriate eltrombopag concentration in pediatric ITP.Methods:This was a single-center,prospective cohort study.Children diagnosed with refractory persistent/chronic ITP and platelet count<30×10^(9)/L were treated with eltrombopag and followed up for at least 2 months.Concentration was detected by high-performance liquid chromatography-mass spectrometry at least 2 weeks after eltrombopag.The clinical characteristics-concentration,concentration-response,and concentration-ADRs were analyzed.Results:A total of 30 patients were enrolled,comprising 13 males and 17 females,with a median age of 72(45-94)months.The median dose and concentration were 1.39(1.09-1.56)mg/kg and 2.70(2.25-4.13)mg/L,respectively.Of the enrolled patients,14 responded to treatment,whereas 16 did not.Additionally,five experienced adverse drug reactions.No linear correlation was observed between eltrombopag concentration and clinical characteristics.The concentration was lower in the response group than in the nonresponse group,but there was no significant difference(t=0.755,P=0.457).Patients who experienced ADRs had a higher concentration than those without ADRs(t=2.538,P=0.017).The area under the receiver operating characteristic curve of ADRs was 0.78(95%confidence interval:0.56-1.00).Youden’s index identified the cutoff point as 4.33 mg/L,with a sensitivity of 88%and a specificity of 60%.Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response.Interpretation:Eltrombopag proves efficacious and well-tolerated for treating pediatric ITP.However,prolonged and high-dose administration may increase the likelihood of ADRs.Thus,examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP.展开更多
目的分析艾曲泊帕(Eltrombopag)在儿童患者中致不良反应(Adverse drug reaction,ADR)的临床特点和一般规律,为其临床合理、安全使用提供参考。方法检索中国知网(CNKI)、万方、维普(VIP)、PubMed等数据库收录的艾曲泊帕致儿童不良反应相...目的分析艾曲泊帕(Eltrombopag)在儿童患者中致不良反应(Adverse drug reaction,ADR)的临床特点和一般规律,为其临床合理、安全使用提供参考。方法检索中国知网(CNKI)、万方、维普(VIP)、PubMed等数据库收录的艾曲泊帕致儿童不良反应相关病例报道,检索时限为建库至2023年5月,并对纳入文献进行统计与分析。结果共纳入文献22篇,应用艾曲泊帕治疗的患儿共800例,ADR共计246例,主要累及消化系统和血液系统,绝大多数ADR为轻症,可自行缓解,或经减停药、对症处理后缓解。结论儿童群体应用艾曲泊帕整体耐受性良好,但仍需加强监测,保障用药安全。展开更多
HuR(human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescen...HuR(human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization(FP) based high-throughput screening(HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay(EMSA), simulation docking and surface plasmon resonance(SPR). Further, we showed that eltrombopag inhibited in vitro cell proliferation of multiple cancer cell lines and macrophages, and the in vivo anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The in vivo data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the in vitro anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells(HUVECs) mediated by macrophages with cell scratch assay and in vitro Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.展开更多
Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,swit...Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA.We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia(ITP)patients.Methods:This prospective,open-label,observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People’s Hospital in China.The study evaluated response rates and platelet counts at different time points after the switch,bleeding events,time to response,duration of response,and adverse events.Results:At 6 weeks after switching,response was observed in 21/49 patients(43%)who switched for inefficacy and 34/47 patients(72%)who switched for non-efficacy-related issues.In the inefficacy group,9/27 patients(33%)responded to eltrombopag,and 12/22 patients(55%)responded to rh-TPO.In the non-efficacy-related group,21/26(81%)and 13/21(62%)patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching,respectively.Response at 6 months was achieved in 24/49 patients(49%)switching for inefficacy and 37/47 patients(79%)switching for non-efficacy issues.In the inefficacy group,13/27 patients(48%)responded to eltrombopag,and 11/22 patients(50%)responded to rh-TPO.In the non-efficacy-related group,22/26 patients(85%)and 15/21 patients(71%)in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching,respectively.Both eltrombopag and rh-TPO were well tolerated.Conclusions:Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA.When the switch was motivated by other reasons,including patient preference and platelet count fluctuations,the probability of response was high.Registration:ClinicalTrials.gov,NCT04214951.展开更多
基金The Natural Science Funding Guidance Project of Liaoning Province,No.2018011494-301345 Talent Program of Shengjing Hospital,China Medical University.
文摘BACKGROUND Eltrombopag is an orally administered thrombopoietin receptor agonist linked to a heightened risk of treatment-related thromboembolism.Both venous and arterial thromboses have been documented in the medical literature.CASE SUMMARY In the absence of nephropathy,a 48-year-old patient receiving eltrombopag for immune thrombocytopenia(ITP)developed renal vein thrombosis and pulmonary embolism.The renal vein thrombus spontaneously resolved during subsequent anticoagulant treatment,restoring venous circulation.CONCLUSION A rapid upsurge in platelets,rather than their absolute number,may trigger thrombotic events in this setting.For patients at high thrombotic risk,individualized eltrombopag dosing and vigilance in platelet monitoring are perhaps needed during treatment of ITP.
文摘Chronic hepatitis C is a public health problem worldwide.Unfortunately,not all patients may benefit from antiviral therapy due to thrombocytopenia.Its causes are represented by portal hypertension and platelet sequestration in the spleen,decreased serum levels or activity of thrombopoietin,the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon.Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients.Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner.Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia.Its indication for other hemopathies or situations(like thrombocytopenia secondary to chemo- or radiotherapy,acute leukemia,myelodysplastic syndroms,acquired and hereditary bone marrow failure,and platelet donors) is under study.Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment.We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus,highlighting the benefits and mentioning possible adverse effects.In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery.Eltrombopag is a solution for many of these patients,which allows them receiving antiviral therapy and sometimes getting a sustained virological response,but they must be well monitored to prevent possible thromboembolic or bone marrow complications or liver failure occurrence.
文摘Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder, defined by a platelet count of less than 100 × 109/L, secondary to impaired production and immune destruction of platelets. Bleeding tendency is the main presentation of this condition. Clinical symptoms and investigations will confirm the diagnosis. Steroid is the first line of treatment. Although Rituximab and Thrombopoietin receptor agonists are useful second line agents in non-pregnant adults, the data about their role in pregnancy are still limited. We present the case of a 30 year old primigravida, who was a known case of chronic ITP since childhood;the course of her disease was fluctuating, for which oral steroids were used accordingly. She presented with gum bleeding and petechial rash with very low platelets count. She was sponsored by the Patient Support Program and was given Eltrombopag during the third trimester. She responded well to Eltrombopag with no noticeable side effects, neither to the mother nor to the baby so far. Eltrombopag has been assigned Category C by the Federal Drugs Agency (FDA) nevertheless there are no well controlled data in the literature about its role in pregnancy.
文摘Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombinant products was associated with formation of autoantibodies. Eltrombopag is an oral thrombopoietin agonist found effective in raising platelet counts in patients with immune thrombocytopenia. The drug has now been found to be useful in raising platelet counts in thrombocytopenia related to liver disease including cirrhosis and chronic viral hepatitis. Although the drug may help enable adequate interferon therapy in patients with HCV infection and help carry out invasive procedures in patients with cirrhosis, concerns have been raised of possible thrombotic complications including portal vein thrombosis. Randomized trials have shown that use of eltrombopag concomitant with pegylated interferon and ribavirin increased the chances of sustained virologic response while decreasing the dose reductions of interferon. The data on use of romiplostim in these clinical indications is also emerging. However, in the future, availability of interferon free regimens is likely to decrease the use of eltrombopag for enabling antiviral therapy. The review discusses the role of eltrombopag in management of liver disease related thrombocytopenia in wake of recent data as also the dosage, precautions and adverse effects associated with its use.
基金Capital’s Funds for Health Improvement and Research:Grant/Award Number:2022-2Z-2099 Beijing Municipal Administration of Hospitals Incubating Program:Grant/Award Number:PX2023044National Natural Science Foundation of China:Grant/Award Number:81970111Funding for Reform and development of Beijing Municipal Health Commission National Key R&D Program of China:Grant/Award Number:2023YFC2706100。
文摘Importance:Eltrombopag has been recommended for pediatric immune thrombocytopenia(ITP).Response and adverse drug reactions(ADRs)varied widely between individuals,even at the same dose of eltrombopag.The appropriate eltrombopag concentration in ITP has not been reported.Objective:This study aims to explore the appropriate eltrombopag concentration in pediatric ITP.Methods:This was a single-center,prospective cohort study.Children diagnosed with refractory persistent/chronic ITP and platelet count<30×10^(9)/L were treated with eltrombopag and followed up for at least 2 months.Concentration was detected by high-performance liquid chromatography-mass spectrometry at least 2 weeks after eltrombopag.The clinical characteristics-concentration,concentration-response,and concentration-ADRs were analyzed.Results:A total of 30 patients were enrolled,comprising 13 males and 17 females,with a median age of 72(45-94)months.The median dose and concentration were 1.39(1.09-1.56)mg/kg and 2.70(2.25-4.13)mg/L,respectively.Of the enrolled patients,14 responded to treatment,whereas 16 did not.Additionally,five experienced adverse drug reactions.No linear correlation was observed between eltrombopag concentration and clinical characteristics.The concentration was lower in the response group than in the nonresponse group,but there was no significant difference(t=0.755,P=0.457).Patients who experienced ADRs had a higher concentration than those without ADRs(t=2.538,P=0.017).The area under the receiver operating characteristic curve of ADRs was 0.78(95%confidence interval:0.56-1.00).Youden’s index identified the cutoff point as 4.33 mg/L,with a sensitivity of 88%and a specificity of 60%.Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response.Interpretation:Eltrombopag proves efficacious and well-tolerated for treating pediatric ITP.However,prolonged and high-dose administration may increase the likelihood of ADRs.Thus,examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP.
文摘目的分析艾曲泊帕(Eltrombopag)在儿童患者中致不良反应(Adverse drug reaction,ADR)的临床特点和一般规律,为其临床合理、安全使用提供参考。方法检索中国知网(CNKI)、万方、维普(VIP)、PubMed等数据库收录的艾曲泊帕致儿童不良反应相关病例报道,检索时限为建库至2023年5月,并对纳入文献进行统计与分析。结果共纳入文献22篇,应用艾曲泊帕治疗的患儿共800例,ADR共计246例,主要累及消化系统和血液系统,绝大多数ADR为轻症,可自行缓解,或经减停药、对症处理后缓解。结论儿童群体应用艾曲泊帕整体耐受性良好,但仍需加强监测,保障用药安全。
基金supported by National Natural Science Foundation of China(81573579)the New Interdisciplinary Subject Funding Program for Shanghai Traditional Chinese Medicine(E2-F18003,China)+3 种基金Shanghai Municipal Education Commission(SMEC,2019-01-07-00-10-E00072,China)Science and Technology Commission of Shanghai Municipality(STCSM,18401933500,China)Postdoctoral Science Foundation of China(A2-X1802408)Shanghai Municipal Commission of Health and Family Planning(2018YQ003,China)
文摘HuR(human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization(FP) based high-throughput screening(HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay(EMSA), simulation docking and surface plasmon resonance(SPR). Further, we showed that eltrombopag inhibited in vitro cell proliferation of multiple cancer cell lines and macrophages, and the in vivo anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The in vivo data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the in vitro anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells(HUVECs) mediated by macrophages with cell scratch assay and in vitro Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.
基金Beijing Natural Science Foundation(No.H2018206423)National Natural Science Foundation of China(No.81970113)+1 种基金Key Program of National Natural Science Foundation of China(No.81730004)National Key Research and Development Program of China(No.2017YFA0105503)。
文摘Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA.We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia(ITP)patients.Methods:This prospective,open-label,observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People’s Hospital in China.The study evaluated response rates and platelet counts at different time points after the switch,bleeding events,time to response,duration of response,and adverse events.Results:At 6 weeks after switching,response was observed in 21/49 patients(43%)who switched for inefficacy and 34/47 patients(72%)who switched for non-efficacy-related issues.In the inefficacy group,9/27 patients(33%)responded to eltrombopag,and 12/22 patients(55%)responded to rh-TPO.In the non-efficacy-related group,21/26(81%)and 13/21(62%)patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching,respectively.Response at 6 months was achieved in 24/49 patients(49%)switching for inefficacy and 37/47 patients(79%)switching for non-efficacy issues.In the inefficacy group,13/27 patients(48%)responded to eltrombopag,and 11/22 patients(50%)responded to rh-TPO.In the non-efficacy-related group,22/26 patients(85%)and 15/21 patients(71%)in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching,respectively.Both eltrombopag and rh-TPO were well tolerated.Conclusions:Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA.When the switch was motivated by other reasons,including patient preference and platelet count fluctuations,the probability of response was high.Registration:ClinicalTrials.gov,NCT04214951.
