重组人血小板生成素治疗脓毒症相关性血小板减少症的临床效果分析
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摘要
目的研究在脓毒症相关性血小板减少症患者的临床治疗中实施重组人血小板生成素治疗的临床疗效。方法经北京大学深圳医院和中山大学孙逸仙纪念医院伦理委员会批准,研究日期于2016年8月至2018年7月,选择两家医院脓毒症伴血小板减少患者共60例展开研究,按治疗方法差异分为两组,重组人血小板生成素(rhTPO)组和乌司他丁组,前者实施rhTPO治疗,15000 U重组人血小板生成素皮下注射,1次/d,1周为1疗程;后者实施乌司他丁治疗,300 000 U/天的乌司他丁,1周为1疗程。对比分析治疗前后两组患者血小板计数、临床相关指标以及炎性指标改善情况。结果观察组治疗前和治疗后3、5、7天时血小板计数分别为50.54±20.58×10~9/L;64.20±10.18×10~9/L;72.61±18.56×10~9/L; 105.60±20.19×10~9/L血小板计数明显较对照高,P<0.05。两组经治疗后各指标虽有改善但ALT未见有明显变化,观察组Cr、PT、RBC、WBC较对照组改善明显;观察组炎性因子IL-6、IL-8明显较对照组低,P<0.05。结论 rhTPO能够提高脓毒症相关性血小板减少症患者的血小板水平且安全,实施rhTPO可能有助改善于脓毒症患者病理过程。
Objective To investigate the clinical efficacy of recombinant human thrombopoietin(rhTPO) in the clinical treatment of patients with sepsis-associated thrombocytopenia. Methods Approved by the Peking University Shenzhen hospital and SUN Yat-senMemorial Hospital, SUN Y at-sen Memorial Hospital University ethics committee, the study was conducted from August 2016 to July 2018. Sixty septic patients with thrombocytopenia from two hospitals were included in the study. Subjects were divided into two groups based on treatments they received : human recombinant platelet hormone(rhTPO) and ulinastatin group. The former received rhTPO treatments, with a dosage of 15000 U human recombinant platelet hormone(shenyang junior pharmaceutical co., LTD., S20050048, approved by the drug properties:Biological products, 15000 units/1 mL/bottle) subcutaneously, 1 time/d, 1 week for a course of treatment. The latter received ulinastatin 300, 000 U/d(GuangdongTianpu biochemical pharmaceutical co.,LTD., national drug approval word H19990134) intravenously for a course of 1 week. The platelet count, relevant other clinical and inflammatory indicators were compared and analyzed before and after treatment. Results The platelet count of the observation group before treatment and 3, 5 and 7 days after treatment were 50.54±20.58×10~9/L; 64.20±10.18×109/L; 72.61 ± 18.56×10~9/L; 105.60±20.19×10~9/L respectively, which were significantly higher than that of the control(all P values <0.05). ALT in two group had not improved, but the levels of Cr, PT, RBC and WBC showed significantly improved,(all P values >0.05). The indexes of inflammatory factors in the observation group were significantly lower than those in the control group(P<0.05). Conclusion RhTPO has benefits for the improvement of platelet count among patients with sepsis-related thrombocytopenia and the safety profile is reassuring.
Objective To investigate the clinical efficacy of recombinant human thrombopoietin(rhTPO) in the clinical treatment of patients with sepsis-associated thrombocytopenia. Methods Approved by the Peking University Shenzhen hospital and SUN Yat-senMemorial Hospital, SUN Y at-sen Memorial Hospital University ethics committee, the study was conducted from August 2016 to July 2018. Sixty septic patients with thrombocytopenia from two hospitals were included in the study. Subjects were divided into two groups based on treatments they received : human recombinant platelet hormone(rhTPO) and ulinastatin group. The former received rhTPO treatments, with a dosage of 15000 U human recombinant platelet hormone(shenyang junior pharmaceutical co., LTD., S20050048, approved by the drug properties:Biological products, 15000 units/1 mL/bottle) subcutaneously, 1 time/d, 1 week for a course of treatment. The latter received ulinastatin 300, 000 U/d(GuangdongTianpu biochemical pharmaceutical co.,LTD., national drug approval word H19990134) intravenously for a course of 1 week. The platelet count, relevant other clinical and inflammatory indicators were compared and analyzed before and after treatment. Results The platelet count of the observation group before treatment and 3, 5 and 7 days after treatment were 50.54±20.58×10~9/L; 64.20±10.18×109/L; 72.61 ± 18.56×10~9/L; 105.60±20.19×10~9/L respectively, which were significantly higher than that of the control(all P values <0.05). ALT in two group had not improved, but the levels of Cr, PT, RBC and WBC showed significantly improved,(all P values >0.05). The indexes of inflammatory factors in the observation group were significantly lower than those in the control group(P<0.05). Conclusion RhTPO has benefits for the improvement of platelet count among patients with sepsis-related thrombocytopenia and the safety profile is reassuring.
引文
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[16]Kong Z,Qin P,Xiao S,et al.A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy[J].Blood,2017,130(9):1097.
[17]Wang Y,Wang Z,Wu L,et al.Recombinant human thrombopoietin is an effective treatment for thrombocytopenia in hemophagocyticlymphohistiocytosis[J].Ann Hematol,2013,92(12):1695-1699.
[18]Xu Y,Song X,Du F,et al.A randomized controlled study of rhTPO and rhIL-11 for the prophylactic treatment of chemotherapy-induced thrombocytopenia in non-small cell lung cancer[J].J Cancer,2018,9(24):4718-4725.
[19]Wang G,Chen W,Wu Y,et al.Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma:A cohort study[J].Medicine(Baltimore),2017,96(50):e9302.
[2]Guo F,Wang X,Huan J,et al.Association of platelet counts decline and mortality in severely burnt patients[J].J Crit Care,2012,27(5):529.e1-7.
[3]Lupia E,Bosco O,Mariano F,et al.Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation[J].J ThrombHaemost,2009,7(6):1000-1008.
[4]Zakynthinos SG,Papanikolaou S,Theodoridis T,et al.Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients[J].Crit Care Med,2004,32(4):1004-1010.
[5]Sharma B,Sharma M,Majumder M,et al.Thrombocytopenia in septic shock patients--a prospective observational study of incidence,risk factors and correlation with clinical outcome[J].Anaesth Intensive Care,2007,35(6):874-880.
[6]Plessier A,Denninger MH,Consigny Y,et al.Coagulation disorders in patients with cirrhosis and severe sepsis[J].Liver Int,2003,23(6):440-448.
[7]Rhodes A,Evans LE,Alhazzani W,et al.Surviving Sepsis Campaign:International Guidelines for Management of Sepsis and Septic Shock:2016[J].Intensive Care Med,2017,43(3):304-377.
[8]Wu Q,Ren J,Wu X,et al.Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia:a prospective study[J].J Crit Care,2014,29(3):362-366.
[9]Levi M,Opal SM.Coagulation abnormalities in critically ill patients[J].Crit Care,2006,10(4):222.
[10]Lupia E,Goffi A,Bosco O,Montrucchio G.Thrombopoietin as biomarker and mediator of cardiovascular damage in critical diseases[J].Mediators Inflamm,2012,2012:390892.
[11]Montrucchio G,Brizzi MF,Calosso G,et al.Effects of recombinant human megakaryocyte growth and development factor on platelet activation[J].Blood,1996,87(7):2762-2768.
[12]Tibbles HE,Navara CS,Hupke MA,et al.Thrombopoietin induces p-selectin expression on platelets and subsequent platelet/leukocyte interactions[J].Biochem Biophys Res Commun,2002,292(4):987-991.
[13]Brizzi MF,Battaglia E,Rosso A,et al.Regulation of polymorphonuclear cell activation by thrombopoietin[J].J Clin Invest,1997,99(7):1576-1584.
[14]Lupia E,Spatola T,Cuccurullo A,et al.Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum[J].Basic Res Cardiol,2010,105(5):609-620.
[15]章渭方.重组人血小板生成素治疗脓毒症相关血小板减少症患者的临床研究[J].中华危重症医学杂志_电子版,2016,9(5):300-308.
[16]Kong Z,Qin P,Xiao S,et al.A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy[J].Blood,2017,130(9):1097.
[17]Wang Y,Wang Z,Wu L,et al.Recombinant human thrombopoietin is an effective treatment for thrombocytopenia in hemophagocyticlymphohistiocytosis[J].Ann Hematol,2013,92(12):1695-1699.
[18]Xu Y,Song X,Du F,et al.A randomized controlled study of rhTPO and rhIL-11 for the prophylactic treatment of chemotherapy-induced thrombocytopenia in non-small cell lung cancer[J].J Cancer,2018,9(24):4718-4725.
[19]Wang G,Chen W,Wu Y,et al.Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma:A cohort study[J].Medicine(Baltimore),2017,96(50):e9302.