Thrombopoietin ameliorates doxorubicin-induced toxicities in H9c2 myocardiocytes by inhibiting oxidative stress through the SIRT1/p38 MAPK signaling pathway

Objective:To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1(SIRT1)signaling pathway.Methods:H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay.The protein expressions of SIRT1 and p38 MAPK were measured by Western blot.RT-qPCR was also used to determine SIRT1 mRNA expression.In addition,intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated.Results:Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability.It also increased SIRT1 and decreased p-p38 MAPK protein expressions.In addition,thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress,and enhanced antioxidant enzyme activities.However,silencing SIRT1 abrogated the protective effects of thrombopoietin,as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels.Conclusions:Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway.However,its protective effects need to be further verified in animal tests.

Effects of thrombopoietin pre-treatment on peri-liver transplantation thrombocytopenia in a mouse model of cirrhosis with hypersplenism

BACKGROUND During cirrhosis,the liver is impaired and unable to synthesize and clear thrombopoietin properly.At the same time,the spleen assumes the function of hemofiltration and storage due to liver dysfunction,resulting in hypersplenism and excessive removal of platelets in the spleen,further reducing platelet count.When liver function is decompensated in cirrhotic patients,the decrease of thrombopoietin(TPO)synthesis is the main reason for the decrease of new platelet production.This change of TPO leads to thrombocytopenia and bleeding tendency in cirrhotic patients with hypersplenism.AIM To investigate the clinical efficacy of recombinant human TPO(rhTPO)in the treatment of perioperative thrombocytopenia during liver transplantation in cirrhotic mice with hypersplenism.METHODS C57BL/6J mice and TPO receptor-deficient mice were used to establish models of cirrhosis with hypersplenism.Subsequently,these mice underwent orthotopic liver transplantation(OLT).The mice in the experimental group were given rhTPO treatment for 3 consecutive days before surgery and 5 consecutive days after surgery,while the mice in the control group received the same dose of saline at the same frequency.Differences in liver function and platelet counts were determined between the experimental and control groups.Enzyme-linked immunosorbent assay was used to assess the expression of TPO and TPO receptor(c-Mpl)in the blood.RESULTS Preoperative administration of rhTPO significantly improved peri-OLT thrombocytopenia in mice with cirrhosis and hypersplenism.Blocking the expression of TPO receptors exacerbated peri-OLT thrombocytopenia.The concentration of TPO decreased while the concentration of c-Mpl increased in compensation in the mouse model of cirrhosis with hypersplenism.TPO pre-treatment significantly increased the postoperative TPO concentration in mice,which in turn led to a decrease in the c-Mpl concentration.TPO pre-treatment also significantly enhanced the Janus kinase(Jak)/signal transducers and activators of transcription pathway protein expressions in bone marrow stem cells of the C57BL/6J mice.Moreover,the administration of TPO,both before and after surgery,regulated the levels of biochemical indicators,such as alanine aminotransferase,alkaline phosphatase,and aspartate aminotransferase in the C57BL/6J mice.CONCLUSION Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism,who underwent liver transplantation but also significantly enhanced the perioperative liver function.

血小板生成素thrombopoietin对神经保护作用的体外研究

目的体外研究血小板生成素(TPO,一种调控巨核细胞和血小板生成的因子),对神经祖细胞C17.2的保护作用。方法建立无血清条件下C17.2细胞凋亡的模型,用TPO不同浓度处理C17.2细胞,利用MTT、Western blotting、流式细胞技术等方法检测TPO对C17.2细胞的保护作用。结果不同浓度的TPO(0、1、10、50、100、200ng/ml)都能促进C17.2细胞增殖,并且具有剂量依赖性。TPO使磷酸化AKT水平增加,促进神经祖细胞增殖,LY294002可以阻止细胞的增殖。用流式细胞仪方法检测表达Annexin V的细胞减少。结论体外研究显示TPO通过激活PI3K/AKT信号通路,对神经祖细胞C17.2起保护作用,这一发现为临床上神经损伤的治疗提供了新的思路。

Trombinol,a bioactive fraction of Psidium guajava,stimulates thrombopoietin expression in HepG2 cells

Objective:To study the regulation of trombinol on thrombopoietin,an essential regulator of thrombocyte production.Methods:Effect of trombinol on thrombopoietin regulation was evaluated at the m RNA and protein levels in human hepatoma Hep G2 cells.The m RNA expressions were revealed by PCR and real-time PCR,while the protein expressions were analyzed using western blotting and human ELISA kit.Statistical differences between the test were determined by student's t-test with P < 0.05 was considered statistically significant.Results:Trombinol significantly increased the expression of thrombopoietin at the level of m RNA and protein secretion in Hep G2 cell lines.Trombinol with the concentration of15 mg/m L,positively induces 2.5-fold of thrombopoietin expression.Up-regulation of GABP,a transcription factor of thrombopoietin,is suggested to be involved in cellular regulatory mechanisms of trombinol.Here,our result shows convincing evidence that trombinol affects the thrombopoietin productions in vitro.This molecular explanation of thrombopoietin's stimulating function is in line with the traditional use of Psidium guajava for treatment of diseases involving thrombocytopenia.Conclusions:Thrombopoietin stimulating function of trombinol could be potentially considered as one of alternative treatment for thrombocytopenia-related cases,including post chemotherapy shock,dengue fever and liver failure.

Recombinant human thrombopoietin treatment in patients with chronic liver disease-related thrombocytopenia undergoing invasive procedures:A retrospective study

BACKGROUND Chronic liver disease(CLD)related thrombocytopenia increases the risk of bleeding and poor prognosis.Many liver disease patients require invasive procedures or surgeries,such as liver biopsy or endoscopic variceal ligation,and most of them have lower platelet counts,which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders.Unfortunately,there is no defined treatment modality for CLD-induced thrombocytopenia.Recombinant human thrombopoietin(rhTPO)is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy;however,there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.AIM To evaluate the efficacy of rhTPO in the treatment of patients with CLDassociated thrombocytopenia undergoing invasive procedures.METHODS All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021.Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia.Adverse events related to treatment,such as bleeding,thrombosis,and disseminated intravascular coagulation,were also investigated.RESULTS Among the enrolled patients,78(78%)showed a platelet count increase after rhTPO use,while 22(22%)showed no significant change in platelet count.The mean platelet count after rhTPO treatment in all patients was 101.53±81.81×10^(9)/L,which was significantly improved compared to that at baseline(42.88±16.72×10^(9)/L),and this difference was statistically significant(P<0.001).In addition,patients were further divided into three subgroups according to their baseline platelet counts(<30×10^(9)/L,30-50×10^(9)/L,>50×10^(9)/L).Subgroup analyses showed that the median platelet counts after treatment were significantly higher(P<0.001,all).Ninety(90%)patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO.No serious adverse events related to rhTPO treatment were observed.Overall,rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.CONCLUSION rhTPO can improve platelet count,reduce the risk of bleeding,and decrease the platelet transfusion rate,which may promote the safety of invasive procedures and improve overall survival of patients with CLD.

Thrombopoietin induced proliferation and differentiation of fetal liver CD34^+ cells with phenotype change from hemopoiesis to neurogenesis

BACKGROUND： Previous studies have reported a neurotrophin-like motif in the N-terminal receptor binding region of the thrombopoietin （TPO） molecule, and have described localization of TPO and TPO receptor in the brain. Therefore, it is believed that TPO may be involved in regulation of neurogenesis. OBJECTIVE： To validate the effect of TPO on trans-differentiation, or differentiation from hematopoietic stem cells （HSCs） to neural stem cells （NSCs）. DESIGN, TIME AND SETTING： Comparative studies were performed from March 2004 to April 2007 at the Department of Experimental Medicine, Northern Hospital, and the Department of Immunology, Fourth Military Medical University of Chinese PLA. MATERIALS： Human fetal liver （FL） was obtained from fetuses after water-balloon abortion. Gestational age ranged from 16 to 20 weeks. The study was approved by the Institutional Review Board and Ethics Committee of the Northern Hospital. TPO was kindly provided by Genentech Inc （USA）. Iscove＇s Modified Dulbecco＇s Medium （IMDM） and neurobasalTM medium were purchased from Invitrogen （USA）. MACS CD34 multisort kit was purchased from Miltenyi Biotec （Germany）. METHODS： CD34^＋ cells were isolated from human FL mononuclear cells using MACS CD34 multisort kit and cultured at 1 × 10^5/mL in IMDM, containing TPO for 60 days with weekly changes of half of the medium. After culturing for 30 and 60 days, the TPO-induced cells were resuspended in neurobasalTM medium containing 10% fetal brain extracts and plated in an 8-well BIOCOAT poly-D-Lysine Culture Slide and cultured for another 7 days. MAIN OUTCOME MEASURES： Cell number, viability, phenotype and expression of hemopoiesis-related and neurogenesis-related proteins were examined by trypan blue exclusion with hemocytometer, immunoblot, immunocytochemistry and flow cytometry. RESULTS： After 60 days of induction with TPO, the cell number increased by 4.6-fold compared to the initial culture. Although the proportion of the cells expressing the hemopoietic stem cell associated antigen （CD34） decreased steadily, both proportions of the cultured FL-derived CD34^＋cells expressing CD41a and CD61 remained unchanged, which still accounted for 10%. Noticeably, the proportions of the cells expressing nestin and epidermal growth factor receptor increased significantly （both 〉 50%）, whereas the expression of more mature neural or glial proteins [microtubule-associated protein-2 （MAP2）, glial fibrillary acidic protein （GFAP）, oligodendrocyte marker 04 （04）] markers on the cultured fetal liver derived-CD34^＋ cells were at lower levels. After another 7 days incubation in neurobasalTM medium, these TPO-induced cells formed neurospheres, which were labeled with nestin, and differentiated into cells with morphological characteristics of neurons, astrocytes and oligodendrocytes, which were labeled with MAP-2, GFAE and 04, respectively. CONCLUSION： TPO can induce FL-derived HSCs to differentiate or trans-differentiate into NSCs and its progenitors.

THE STIMULATING EFFECT OF HEPARIN IN SYNERGY WITHTHROMBOPOIETIN ON MEGAKARYOCYTOPOIESISAND THROMBOPOIESIS

Objective To demonstrate whether heparin could act synergically with thrombopoietin (TPO) instimulating megakaryocytopoiesis and thrombopoiesis. Methods Megakaryocytic leukemia cell line M- 07e,human cord blood CD34+ cells and Balb/c mice were used for studies. The effectS of hoparin and/or TPO onmegakaryocytopoiesis and thrombopoiesis were studied by [ 3H ] - TdR incoroperation assay, CFU- MK plasmicsemi- solid culture and experiment in Balb/c mice in vivo. In addition, M- 07e cells were used as targets tofurther investigate the possible molecular mechanism by which heparin might act synergically with TPO throughNorthern and Western blot analyses. Results Heparin can act synergically with TPO in stimulating theproliferation of leukemia cell line M- 07e, growth of CFU- MK from human cord blood CD34+ cells andmegakaryocytopoiesis and thrombopoiesis in vivo in mice, possibly by antagonizing downregulation of c- mplexpression by TPO at the level of mRNA transcription, and increasing the phosphotyrosine content Of Jak2,triggered by TPO. Conclusion Heparin participated in positive regulation of megakaryocytopoiesis andthrombopoiesis by enhancing the megakaryocytopoietic activities of TPO, and the mechanism of which might beinvolved in the modification of the molecules c- mpl and Jak2 on the way of signal transduction triggered by TPO.

Correlation between thrombopoietin and inflammatory factors,platelet indices,and thrombosis in patients with sepsis:A retrospective study

BACKGROUND Thrombopoietin(TPO)is a primary regulator of thrombopoiesis in physiological conditions.TPO,in combination with its specific cytokine receptor c-Mpl,drives platelet production by inducing the proliferation and differentiation of megakaryocytes.However,the role of TPO in sepsis is not well determined.The elevated levels of TPO are often accompanied by a decrease of platelet count(PLT)in systemic infected conditions,which is contrary to the view that TPO promotes platelet production under physiological conditions.In addition,whether TPO mediates organ damage in sepsis remains controversial.AIM To explore the relationships between TPO and inflammatory factors,platelet indices,and thrombotic indicators in sepsis.METHODS A total of 90 patients with sepsis diagnosed and treated at the emergency medicine department of The First People’s Hospital of Foshan between January 2020 and March 2021 were enrolled in this study.In addition,110 patients without sepsis who came to the emergency medicine department were included as controls.Clinical and laboratory parameters including age,gender,TPO,blood cell count in peripheral blood,platelet indices,inflammatory factors such as high-sensitivity Creactive protein(hs-CRP),interleukin(IL)-21,and IL-6,organ damage indicators,and thrombotic indicators were collected and analyzed by using various statistical approaches.RESULTS The results showed that the TPO levels were higher in the sepsis group than in controls[86.45(30.55,193.1)vs 12.45(0.64,46.09)pg/mL,P<0.001],but PLT was lower(P<0.001).Multivariable analysis showed that white blood cell count(WBC)[odds ratio(OR)=1.32;95%confidence interval(CI):1.01-1.722;P=0.044],TPO(OR=1.02;95%CI:1.01-1.04;P=0.009),IL-21(OR=1.02;95%CI:1.00-1.03;P=0.019),troponin I(OR=55.20;95%CI:5.69-535.90;P=0.001),and prothrombin time(PT)(OR=2.24;95%CI:1.10-4.55;P=0.027)were independent risk factors associated with sepsis.TPO levels were positively correlated with IL-21,IL-6,hs-CRP,creatinine,D-dimer,PT,activated prothrombin time,international normalized ratio,fibrinogen,WBC count,and neutrophil count,and negatively correlated with PLT,thrombin time,red blood cell count,and hemoglobin concentration(P<0.05).Receiver operating characteristic analysis showed that TPO had fair predictive value in distinguishing septic patients and non-septic patients(the area under the curve:0.788;95%CI:0.723-0.852;P<0.001).With an optimized cutoff value(28.51 pg/mL),TPO had the highest sensitivity(79%)and specificity(65%).CONCLUSION TPO levels are independently associated with sepsis.High TPO levels and low PLT suggest that TPO might be an acute-phase response protein in patients with infection.

Thrombopoietin-receptor agonists in perioperative treatment of patients with chronic liver disease

Thrombocytopenia is a multifactorial disorder that is common in patients with chronic liver disease(CLD),leading to challenging perioperative planning.As thrombocytopenia in CLD is associated with thrombopoietin(TPO)deficiency,the use of TPO-receptor agonists(TPO-RAs)to increase platelet counts is a promising approach.This has led to the development of various TPO-RAs,including romiplostim,eltrombopag,avatrombopag,and lusutrombopag.Of these,only avatrombopag and lusutrombopag are approved by the United States Food and Drug Administration for the perioperative treatment of thrombocytopenia in patients with CLD.Platelet transfusion is commonly used for the clinical management of thrombocytopenia in patients with CLD undergoing invasive procedures.However,the limitations and possible risks of transfusion,including short duration of efficacy,development of antiplatelet antibodies,risk of infections and such complications as transfusion-related acute lung injury or circulatory overload,and possibility of refractoriness,limit its use.Moreover,there is no consensus among guidelines as to the platelet count at which transfusions are indicated.Results from studies using TPO-RAs perioperatively in patients with thrombocytopenia and CLD are promising and provide an alternative to platelet transfusions in the pre-and post-operative setting.These TPO-RAs are the subject of this review,with focus on their use in the perioperative setting in patients with thrombocytopenia,associated supporting clinical trials,efficacy and safety data,and their use with respect to platelet transfusions.

Recombinant human thrombopoietin in alleviating endothelial cell injury in sepsis

Background To evaluate the effect of recombinant human thrombopoietin(rhTPO)on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.Methods This retrospective observational study involved patients with sepsis(diagnosed according to Sepsis 3.0)admitted to Shanghai General Hospital intensive care unit from January 1,2019 to December 31,2022.Patients were divided into two groups(control and rhTPO)according to whether they received rhTPO.Baseline information,clinical data,prognosis,and survival status of the patients,as well as inflammatory factors and immune function indicators were collected.The main monitoring indicators were endothelial cell-specific molecule(ESM-1),human heparin-binding protein(HBP),and CD31;secondary monitoring indicators were interleukin(IL)-6,tumor necrosis factor(TNF)-α,extravascular lung water index,platelet,antithrombin III,fibrinogen,and international normalized ratio.We used intraperitoneal injection of lipopolysaccharide(LPS)to establish a mouse model of sepsis.Mice were randomly divided into four groups:normal saline,LPS,LPS+rhTPO,and LPS+rhTPO+LY294002.Plasma indicators in mice were measured by enzyme-linked immunosorbent assay.Results A total of 84 patients were included in the study.After 7 days of treatment,ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1(median=38.6[interquartile range,IQR:7.2 to 67.8]pg/mL vs.median=23.0[IQR:−15.7 to 51.5]pg/mL,P=0.008).HBP and CD31 also decreased significantly in the rhTPO group compared with the control group(median=59.6[IQR:−1.9 to 91.9]pg/mL vs.median=2.4[IQR:−23.2 to 43.2]pg/mL;median=2.4[IQR:0.4 to 3.5]pg/mL vs.median=−0.6[IQR:−2.2 to 0.8]pg/mL,P<0.001).Inflammatory markers IL-6 and TNF-αdecreased more significantly in the rhTPO group than in the control group compared with day 1(median=46.0[IQR:15.8 to 99.1]pg/mL vs.median=31.2[IQR:19.7 to 171.0]pg/mL,P<0.001;median=17.2[IQR:6.4 to 23.2]pg/mL vs.median=0.0[IQR:0.0 to 13.8]pg/mL,P=0.010).LPS+rhTPO-treated mice showed significantly lower vascular von Willebrand factor(P=0.003),vascular endothelial growth factor(P=0.002),IL-6(P<0.001),and TNF-α(P<0.001)than mice in the LPS group.Endothelial cell damage factors vascular von Willebrand factor(P=0.012),vascular endothelial growth factor(P=0.001),IL-6(P<0.001),and TNF-α(P=0.001)were significantly elevated by inhibiting the PI3K/Akt pathway.Conclusion rhTPO alleviates endothelial injury and inflammatory indices in sepsis,and may regulate septic endothelial cell injury through the PI3K/Akt pathway.

血小板生成素受体激动剂治疗化疗相关性血小板减少症的研究现状

化疗相关性血小板减少症(chemotherapy-induced thrombocytopenia, CIT)仍是目前肿瘤治疗的严重并发症,既往针对CIT的处理主要为输注血小板、使用重组人白介素-11(recombinanthumaninterleukin-11,rhIL-11)及重组人血小板生成素(recombinanthuman thrombopoietin, rhTPO)等,但对一些难治性CIT,效果有限。近年来,新型血小板生成素受体激动剂(thrombopoietin receptor agonists, TPO-RAs)已上市并用于血小板减少症,但尚未批准用于CIT治疗。本文对TPO-RAs类药物在CIT方面已开展的临床研究进行汇总,结果显示罗米司亭、艾曲泊帕、阿伐曲泊帕研究相对较多,但多为小样本或单中心回顾性分析,而芦曲泊帕和海曲泊帕尚缺乏治疗CIT的临床研究。

Plasma thrombopoietin levels in patients with aplastic anemia and idiopathic thrombocytopenic purpura

OBJECTIVE: To evaluate the role of thrombopoietin (TPO) in the pathology of chronic thrombocytopenic disease. METHODS: We measured the endogenous plasma concentration of TPO in 40 patients with acquired aplastic anaemia (AA) and in 32 patients with idiopathic thrombocytopenic purpura (ITP) by a sensitive Sandwich enzyme-linked immunosorbent assay (ELISA) and compared the results. RESULTS: Plasma TPO concentrations were significantly higher in AA patients (774 +/- 393 pg/ ml) in comparison with healthy control subjects (55 +/- 34 pg/ml, P 0.05). There was also no relationship between their plasma TPO levels and platelet counts. CONCLUSIONS: TPO levels may be regulated not only by platelets but also by megakaryocytes in AA and ITP, and measurement of TPO levels is useful for diagnosing thrombocytopenia and understanding the pathophysiology of thrombocytopenia.

海曲泊帕治疗实体瘤化疗后血小板Ⅲ、Ⅳ度患者的临床疗效分析

目的探讨海曲泊帕应用于实体瘤化疗后血小板Ⅲ、Ⅳ度患者的临床疗效。方法回顾性分析2022年6月—2023年6月包头市肿瘤医院收治的98例实体瘤化疗后血小板Ⅲ、Ⅳ度患者的临床资料,根据不同治疗方案分为对照组和观察组,分别为48和50例。对照组皮下注射重组人血小板生成素注射液,观察组在对照组基础上口服海曲泊帕。治疗4周后。比较两组患者血小板计数、血小板平均体积、血小板分布宽度、血小板生成素(TPO)、信号转导和转录激活因子3(STAT3)、丝裂原活化蛋白激酶(MAPK)、CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、出血风险分级及不良反应率。结果观察组治疗前后血小板计数、血小板平均体积和血小板分布宽度的差值均高于对照组(P<0.05)。观察组治疗前后TPO、STAT3、MAPK的差值均高于对照组(P<0.05)。观察组治疗前后CD4^(+)/CD8^(+)的差值高于对照组(P<0.05)。两组治疗前后CD4^(+)、CD8^(+)的差值比较,差异均无统计学意义(P>0.05)。观察组出血风险分级低于对照组(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论海曲泊帕应用于实体瘤化疗后血小板Ⅲ、Ⅳ度患者的治疗中,有助于升高血小板水平,安全性良好。

小剂量激素配合血小板生成素受体激动剂方案对成人急性原发性免疫性血小板减少症患者血常规及免疫球蛋白水平表达的影响

目的探讨小剂量激素配合血小板生成素受体激动剂(TPO-RA)方案治疗成人原发性免疫性血小板减少症(ITP)患者的疗效及对患者血常规及免疫球蛋白水平表达的影响。方法选取2019年1月至2022年3月九江市第一人民医院收治的60例成人ITP患者作为研究对象,根据治疗方案的不同分为研究组与对照组,每组30例。对照组给予小剂量激素治疗,研究组给予小剂量激素配合TPO-RA方案治疗。比较两组血常规指标[血小板计数(PLT)、红细胞沉降率(ESR)]、免疫球蛋白[血小板相关免疫球蛋白A(PAIgA)、血小板相关免疫球蛋白G(PAIgG)、血小板相关免疫球蛋白M(PAIgM)]水平、T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+))水平、相关细胞[网织血小板、产板巨核细胞及巨核细胞]水平、临床疗效、不良反应发生情况及生命质量[生命质量综合评定问卷(GQOLI-74)]评分。结果治疗后,研究组PLT高于对照组,ESR低于对照组,差异有统计学意义(P<0.05)。治疗后,研究组PAIgA、PAIgG、PAIgM水平均低于对照组,差异有统计学意义(P<0.05)。治疗后,研究组CD3^(+)、CD4^(+)水平均高于对照组,CD8^(+)水平低于对照组,差异有统计学意义(P<0.05)。治疗后,研究组网织血小板水平低于对照组,巨核细胞数量少于对照组,产板巨核细胞水平高于对照组,差异有统计学意义(P<0.05)。研究组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义。治疗后,研究组物质生活状态、心理功能、身体功能、社会功能评分均高于对照组,差异有统计学意义(P<0.05)。结论小剂量激素配合TPO-RA方案治疗ITP疗效显著,可有效改善患者血常规与免疫球蛋白水平,提高患者生命质量,值得临床推广应用。

TP患者应用IL-11联合重组人血小板生成素治疗的临床疗效及安全性

目的:探讨血小板减少症(TP)患者应用白细胞介素(IL)-11联合重组人血小板生成素注射液治疗的临床疗效及安全性。方法:选取2022年8月至2023年8月在漯河医学高等专科学校第二附属医院接受治疗的150例TP患者,随机均分为常规组与联合组,每组各纳入75例。常规组给予应用IL-11治疗,联合组在常规组的基础上联合应用重组人血小板生成素输注治疗。观察两组患者治疗期间血小板计数的变化,比较血小板计数达标时间;治疗14 d,观察血清学检测指标的变化;出院前统计两组患者不良反应发生情况并比较。结果:治疗3 d、7 d、14 d时,联合组患者血小板计数均高于常规组;联合组患者血小板计数恢复至≥50×10^(9)·L^(-1)时间、≥70×10^(9)·L^(-1)时间、≥100×10^(9)·L^(-1)时间均短于常规组;治疗14 d时,联合组血清促血小板生成素(TPO)、IL-6、肿瘤坏死因子-α(TNF-α)水平均低于常规组,差异均具有统计学意义(P<0.05)。两组患者不良反应总发生率的差异无统计学意义(P>0.05)。结论:IL-11联合重组人血小板生素注射液治疗TP可获得理想的临床疗效,能有效缩短血小板达标时间,且联合方案安全性可靠。

重组人血小板生成素对多发性骨髓瘤患者自体外周血造血干细胞移植术后血小板重建影响的研究

目的:分析重组人血小板生成素(rh TPO)对多发性骨髓瘤(MM)患者自体外周血造血干细胞移植术(APBSCT)后血小板(PLT)重建的影响。方法:回顾性分析在苏州大学附属第一医院一线行APBSCT治疗的147例MM患者的临床资料,根据APBSCT期间是否使用rh TPO分为rh TPO组80例和对照组67例,比较两组患者在PLT植入时间、血制品输注需求量、移植后+14和+100 d PLT恢复至≥50×10^(9)/L和≥100×10^(9)/L的患者比例以及出血发生率等方面的差异。结果:两组患者在性别、年龄、M蛋白类型、初诊时PLT数、APBSCT前诱导治疗中位疗程数、回输的CD34^(+)细胞数方面均无统计学差异(均P>0.05)。rh TPO组患者PLT植入中位时间为10(6-14)d,较对照组11(8-23)d显著缩短(P<0.001)。rh TPO组患者在APBSCT期间的中位PLT输注需求量为15(0-50)U,较对照组20(0-80)U更少(P=0.001)。移植后+14 d时rh TPO组和对照组PLT≥50×10^(9)/L的患者比例分别为66.3%和52.2%,PLT≥100×10^(9)/L的患者比例分别为23.8%和11.9%,比较差异均无统计学意义(P>0.05)。在移植后+100 d时,rh TPO组和对照组PLT≥50×10^(9)/L的患者比例分别为96.3%和89.6%(P>0.05),但rh TPO组PLT≥100×10^(9)/L的患者比例高于对照组(75.0%vs 55.2%,P=0.012)。两组患者在PLT水平低下期间不同部位出血事件的总体发生率无差异,且rh TPO组治疗耐受性良好,肝肾功能异常和感染的发生概率与对照组类似。结论:MM患者在一线行APBSCT时,皮下注射rh TPO药物可以缩短PLT植入时间,减少血制品的需求量,耐受性良好,且在移植后有更多患者达到了PLT高水平的恢复,这对保证APBSCT和MM患者维持治疗期间的安全具有重要意义。

肝移植术后血小板减少的诊断与治疗

血小板减少是肝移植术后常见的并发症之一,其病理生理机制包括血小板生成不足、血小板消耗增多等,严重影响肝移植受者的预后。肝移植术前肝炎病毒感染、术中缺血损伤、术后使用免疫抑制药等多种因素都可能导致肝移植术后血小板减少,尽早发现和有效治疗肝移植术后血小板减少是目前的研究热点。本文结合现有文献资料,从血小板减少的定义、病理生理机制、危险因素、治疗及预防等方面展开综述,探讨肝移植术后血小板减少发生发展及相关诊治策略,旨在优化现有治疗方案,降低移植术后血小板减少发生的风险,改善肝移植受者预后。

不同海拔急性髓系白血病患者化疗前后血清及骨髓造血因子表达水平差异研究

背景化疗是急性髓系白血病(AML)患者重要的治疗手段,最常见的毒副作用是骨髓抑制。各类血细胞的发育增殖、分化受到多种造血因子的调控,不同海拔AML患者化疗后造血因子表达水平是否存在差异及其变化规律尚未明确。目的探讨不同海拔AML患者化疗前后骨髓及血清造血因子表达水平是否存在差异及其变化。方法选取2021—2022年青海省人民医院血液科(中海拔地区1501~2500 m)及中国人民解放军空军军医大学西京医院血液科(低海拔地区500~1500 m)首诊初治的28例AML患者(非M3型)为研究对象,根据就诊医院海拔高低将AML患者分为中海拔组(13例)和低海拔组(15例)。采用WHO抗癌药物急性及亚急性毒性反应分级标准评估患者化疗第8、14、28天骨髓抑制分度;采用酶联免疫吸附法对两组患者化疗前、化疗第8天、化疗第28天血清及骨髓促红细胞生成素(EPO)、FMS样酪氨酸激酶3配体(Flt3-L)、促血小板生成素(TPO)和干扰素γ(IFN-γ)表达水平进行检测并比较。结果化疗第14、28天,低海拔组患者骨髓抑制分度均高于中海拔组(Z=-1.975,P=0.048;Z=-2.049,P=0.040)。化疗第28天,低海拔组血清及骨髓EPO表达水平高于中海拔组(P<0.05);中海拔组化疗第28天血清EPO表达水平低于化疗第8天(P<0.05)。化疗第28天,低海拔组血清及骨髓Flt3-L表达水平均高于中海拔组(P<0.05);两组患者化疗第8天、化疗第28天血清Flt3-L表达水平均高于化疗前,两组患者化疗第28天骨髓Flt3-L表达水平均高于化疗前(P<0.05)。化疗前、化疗第8天、化疗第28天,低海拔组血清TPO表达水平均高于中海拔组(P<0.05);低海拔组患者化疗第8天血清TPO表达水平低于化疗前(P<0.05);化疗第28天,低海拔组骨髓TPO表达水平高于中海拔组(P<0.05);中海拔组化疗第28天骨髓TPO表达水平低于化疗前(P<0.05)。两组患者化疗前后血清及骨髓IFN-γ表达水平组间、组内比较,差异均无统计学意义(P>0.05)。结论低海拔AML患者化疗后骨髓抑制恢复期间造血生长因子EPO、Flt3-L、TPO表达水平高于中海拔,造血抑制因子IFN-γ两组间无明显差异;中海拔AML患者化疗后骨髓抑制分度及程度较低海拔更严重。

阿伐曲泊帕与重组人血小板生成素治疗肝移植后严重血小板减少症的临床疗效

目的探究阿伐曲泊帕与重组人血小板生成素(rhTPO)治疗肝移植后严重血小板减少症的临床疗效。方法回顾性分析安徽医科大学第一附属医院2016年2月至2023年3月之间81例出现肝移植后严重血小板减少症患者的临床资料。81例患者中,38例接受阿伐曲泊帕治疗被分配到阿伐曲泊帕组,43例接受rhTPO治疗被分配到rhTPO组。监测指标包括用药后血小板变化、治疗有效率、术后并发症发生情况、用药后肝肾功能变化和短期生存率。结果用药后第3、5、7、10和15天阿伐曲泊帕组患者的血小板计数明显高于rhTPO组患者(P>0.05),第30天无差异(P<0.05)。阿伐曲泊帕组患者的治疗有效率显著高于rhTPO组(84.2%us58.1%,P<0.05),阿伐曲泊帕组患者的术后感染发生率明显低于rhTPO组(P<0.05)。两组患者在治疗期间出血和血栓发生率以及肝肾功能无明显差异(P>0.05)。结论阿伐曲泊帕和rhTPO均能提升肝移植后严重血小板减少症患者的血小板水平,其中阿伐曲泊帕的临床疗效优于rhTPO。

促血小板生成素调控慢性肝病患者血小板的作用及其临床应用

慢性肝病患者常有血小板减少,其发生机制复杂且尚未被阐明。随着近年来对慢性肝病合并血小板减少的研究深入,研究者们意识到慢性肝病患者的血小板减少不仅与脾功能亢进有关,而且促血小板生成素在其中也起到一定程度的调控作用,文章提出“肝源性促血小板生成素中心的肠-肝调控网络机制”的可能性,就促血小板生成素调控血小板的作用、慢性肝病患者血小板的生物学功能、促血小板生成素在慢性肝病和肝硬化的诊断,以及促血小板生成素与促血小板生成素受体激动剂在慢性肝病血小板减少的治疗应用等方面的研究进展进行综述,为基础及临床相关研究提供新的思路。