重症感染伴血小板减少症患者的临床特点与治疗方法研究
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摘要
目的探讨重症感染合并血小板减少症患者的病因及治疗方案。方法收集2010年1月-2017年6月于医院住院的重症感染伴血小板减少症患者100例的临床资料。监测患者第1天、第3天、第5天血小板计数,100例患者分为未使用人免疫球蛋白组20例和使用人免疫球蛋白组80例,未使用人免疫球蛋白组除采取积极抗感染治疗措施外,不予以其他治疗,使用人免疫球蛋白组同时给予人免疫球蛋白10 g/天静脉滴注,5天为1疗程。每周复查血常规1次,连续观察4周。结果 100例重症感染伴血小板减少症患者,感染部位以消化系统和呼吸系统为主,其中多系统感染7例。100例重症感染伴血小板减少症患者发热27例,体温为37.7～40.0℃;出血11例,表现为各脏器、皮肤和穿刺部位出血;合并感染性休克5例。中性粒细胞增高24例,血培养阳性17例,痰培养阳性24例。病毒感染28例、细菌感染29例,真菌感染15例,未明确病原体28例,病毒感染、细菌感染、真菌感染和未明确感染来源患者血小板计数分别为(71.72±15.61)、(55.36±11.23)、(65.23±12.75)和(61.47±13.94)×10~9/L,差异有统计学意义(P=0.018),进一步两两比较,病毒感染组血小板计数最高,细菌感染造成的血小板减少最低(P<0.05)。观察4周后,使用人免疫球蛋白组血小板计数基本恢复正常58例,未使用人免疫球蛋白组仅有8例血小板计数基本恢复正常,差异有统计学意义(P<0.001)。结论重症感染相关性血小板减少症中以病毒、细菌感染最常见,其次为真菌感染;与病毒感染相比,细菌感染引起血小板降低更明显。中小剂量丙种球蛋白静脉输注对感染相关性血小板减少症安全有效,具有一定的临床价值。
OBJECTIVE To investigate the etiology and treatment of thrombocytopenia patients with severe infection. METHODS The clinical data of 100 patients with severe infection and thrombocytopenia admitted to the hospital from Jan. 2010 to Jun. 2017 were collected. The platelet counts were monitored on the 1st, 3rd, and 5th day. The 100 patients were divided into two groups, 20 patients were included in the "human immunoglobulin not used" group, and the other 80 patients were included in the "human immunoglobulin used" group. No other treatment was given to the "human immunoglobulin not used" group in addition to active anti-infective treatments. The "human immunoglobulin used" group was given intravenous infusion of human immunoglobulin(10 g/day) in addition to active anti-infective treatments, with 5 days as a course of treatment. The blood routine was reviewed once a week for 4 weeks. RESULTS In the 100 cases of severe infection with thrombocytopenia, the main infection sites were the digestive and respiratory systems, including 7 cases of multiple system infection. In the 100 cases of severe infection with thrombocytopenia, 27 patients had fever, with body temperature of 37.7-40.0 ℃, 11 cases showed hemorrhage in various organs, skin and puncture site, and 5 cases had septic shock. There were 24 cases of neutrophil increase, 17 cases of blood culture positive, and 24 cases of sputum culture positive. There were 28 cases of viral infection, 29 cases of bacterial infection, 15 cases of fungal infection, and 28 cases of infection caused by unknown pathogens. The platelet counts of patients with viral infection, bacterial infection, fungal infection and unidentified infection were(71.72±15.61),(55.36±11.23).(65.23±12.75) and(61.47±13.94)×10~9/L, respectively, the difference was significant(P=0.018). Further comparison between the two groups showed that the platelet count was the highest in the virus-infected group and the thrombocytopenia caused by bacterial infection was the lowest(P<0.05). After 4 weeks of observation, the platelet count of 58 cases in the "human immunoglobulin used" group basically returned to normal, while that of 8 cases in the "human immunoglobulin not used" group basically returned to normal(P<0.001). CONCLUSION Infection-related thrombocytopenia is most common with viral and bacterial infections, followed by fungal infections. Bacterial infections cause more pronounced platelet reduction than viral infections. Intravenous infusion of small and medium doses of gamma globulin is safe and effective for infection-related thrombocytopenia, and has certain clinical value.
OBJECTIVE To investigate the etiology and treatment of thrombocytopenia patients with severe infection. METHODS The clinical data of 100 patients with severe infection and thrombocytopenia admitted to the hospital from Jan. 2010 to Jun. 2017 were collected. The platelet counts were monitored on the 1st, 3rd, and 5th day. The 100 patients were divided into two groups, 20 patients were included in the "human immunoglobulin not used" group, and the other 80 patients were included in the "human immunoglobulin used" group. No other treatment was given to the "human immunoglobulin not used" group in addition to active anti-infective treatments. The "human immunoglobulin used" group was given intravenous infusion of human immunoglobulin(10 g/day) in addition to active anti-infective treatments, with 5 days as a course of treatment. The blood routine was reviewed once a week for 4 weeks. RESULTS In the 100 cases of severe infection with thrombocytopenia, the main infection sites were the digestive and respiratory systems, including 7 cases of multiple system infection. In the 100 cases of severe infection with thrombocytopenia, 27 patients had fever, with body temperature of 37.7-40.0 ℃, 11 cases showed hemorrhage in various organs, skin and puncture site, and 5 cases had septic shock. There were 24 cases of neutrophil increase, 17 cases of blood culture positive, and 24 cases of sputum culture positive. There were 28 cases of viral infection, 29 cases of bacterial infection, 15 cases of fungal infection, and 28 cases of infection caused by unknown pathogens. The platelet counts of patients with viral infection, bacterial infection, fungal infection and unidentified infection were(71.72±15.61),(55.36±11.23).(65.23±12.75) and(61.47±13.94)×10~9/L, respectively, the difference was significant(P=0.018). Further comparison between the two groups showed that the platelet count was the highest in the virus-infected group and the thrombocytopenia caused by bacterial infection was the lowest(P<0.05). After 4 weeks of observation, the platelet count of 58 cases in the "human immunoglobulin used" group basically returned to normal, while that of 8 cases in the "human immunoglobulin not used" group basically returned to normal(P<0.001). CONCLUSION Infection-related thrombocytopenia is most common with viral and bacterial infections, followed by fungal infections. Bacterial infections cause more pronounced platelet reduction than viral infections. Intravenous infusion of small and medium doses of gamma globulin is safe and effective for infection-related thrombocytopenia, and has certain clinical value.
引文
[1] 于倩,王晔恺,姚燕珍,等.36例新布尼亚病毒感染致发热伴血小板减少综合征血清生化酶谱聚类分析[J].中国卫生检验杂志,2018,28(22):2764-2765,2772.
[2] 国家老年疾病临床医学研究中心(解放军总医院),《感染诱发的老年多器官功能障碍综合征诊治中国专家共识》撰写组,边素艳,等.感染诱发的老年多器官功能障碍综合征诊治中国专家共识[J].中华老年多器官疾病杂志,2018,17(1):3-15.
[3] 吴骎,任建安.外科感染合并血小板减少诊治进展[J].中国实用外科杂志,2016,36(2):241-244.
[4] 崔小波,王定芳.新型布尼亚病毒感染致发热伴血小板减少综合征1例报告[J].中国病原生物学杂志,2011,6(9):720.
[5] 郭宏岗,沈建良.93例血小板减少症的病因分析[J].中外医疗,2016,35(21):45-48.
[6] Wasserkrug Naor A ,Lindemann DM ,Schreeg ME,et al.Clinical,morphological,and molecular characterization of an undetermined Babesia species in a maned wolf (Chrysocyon brachyurus)[J].Ticks Tick Borne Dis,2019,10(1):124-126.
[7] Tagami T,Matsui H,Fushimi K,et al.Intravenous immunoglobulin and mortality in pneumonia patients with septic shock:an observational nationwide study[J].Clin Infect Dis,2015,61(3):385-392.
[8] 孙建,吴伟东.脓毒症相关性血小板减少症的危险因素及预后分析[J].中华危重症医学杂志(电子版),2014,7(3):177-181.
[9] 吴安华,李春辉.重症感染的诊断与治疗 [J] .中华急诊医学杂志,2011,20(3):334-336.
[10] 中华医学会重症医学分会.中国严重脓毒症/脓毒性休克治疗指南(2014) [J] .中华内科杂志,2015,54(6):557-581.
[11] Qi L,Fan W,Xia X,et al.Nosocomial outbreak of Candida parapsilosis sensustricto fungaemia in a neonatal intensive care unit in China[J].J Hosp Infect,2018,100(4):e246-e252.
[12] Nishio Y ,Kawano Y,Kawada JI,et al.A case of refractory cytomegalovirus-related thrombocytopenia that achieved complete remission without antiviral therapy[J].J Infect Chemother,2018,24(12):995-997.
[13] 孔海平,吴小花.肠道病毒感染伴血小板减少症新生儿的护理[J].中国现代药物应用,2012,6(9):110-111.
[14] Stearns V,Brufsky AM ,Verma S,et al.Expanded-access study of palbociclib in combination with letrozole for treatment of postmenopausal women with hormone receptor-positive,HER2-negative advanced breast cancer[J].Clin Breast Cancer,2018,18(6):e1239-e1245.
[15] Karnisova L,Hradsky O ,Blahova K,et al.Complement activation is associated with more severe course of diarrhea-associated hemolyticuremic syndrome,a preliminary study[J].Eur J Pediatr,2018,177(12):1837-1844.
[16] Fajgenbaum DC.Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease[J].Blood,2018,132(22):2323-2330.
[17] 韩常新,孙艾军,蒲春文,等.新型布尼亚病毒感染致发热伴血小板减少综合征的流行病学特征及预后影响指标分析[J].中华医院感染学杂志,2019,29(2):171-174.
[18] Soares MO,Welton NJ,Harrison DA,et al.Intravenous immunoglobulin for severe sepsis and septic shock:clinical effectiveness,cost-effectiveness and value of a further randomised controlled trial[J].Crit Care,2014,18(6):649.
[19] Mancini N,Sambri V,Corti C,et al.Cost-effectiveness of blood culture and a multiplex real-time PCR in hematological patients with suspected sepsis:an observational propensity score-matched study[J].Expert Rev Mol Diagn,2014,14(5):623-632.
[20] Rimmer E,Kumar A,Doucette S,et al.Activated protein C and septic shock:a propensity-matched cohort study*[J].Crit Care Med,2012,40(11):2974-2981.
[21] Scriven JE ,Scobie A ,Verlander NQ,et al.Mycobacterium chimaera infection following cardiac surgery in the United Kingdom:clinical features and outcome of the first 30 cases[J].Clin Microbiol Infect,2018,24(11):1164-1170.
[22] Amer A,Kaidar M,Tasher D,et al.Epstein-Barr virus infection was associated with nephrotic syndrome,severe thrombocytopenia and coombs-positive haemolytic anaemia[J].Arch Dis Child,2018,107(11):2030-2031.
[23] 陶文元,陶欣.新型布尼亚病毒感染致发热伴血小板减少综合8例报告[J].江苏大学学报(医学版),2011,21(1):91-92.
[24] Schubert J,Weissbrich B.Detection of virus-specific intrathecally synthesised immunoglobulin G with a fully automated enzyme immunoassay system[J].BMC Neurology,2007,7(1):12-16.
[25] Miroslav Pohanka.Monoclonal and polyclonal antibodies production - preparation of potent biorecognition element[J].J Appl Biomed,2009,7(3):115.
[26] Fesel C,Goulart LF,Silva Neto A,et al.Increased polyclonal immunoglobulin reactivity toward human and bacterial proteins is associated with clinical protection in human Plasmodium infection[J].Malar J,2005,4(1):5-12.
[27] Djordjevic D,Pejovic J,Surbatovic M,et al.Prognostic value and daily trend of interleukin-6,neutrophil CD64 expression,C-reactive protein and lipopolysaccharide-binding protein in critically ill patients:reliable predictors of outcome or not?[J].J Med Biochem,2015,34(4):431-439.
[28] Barie PS,Hydo LJ,Shou J,et al.Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection[J].Surg Infect (Larchmt),2005,2005,6:41-54.
[29] Petrikkos GL,Christofilopoulou SA,Tentolouris NK,et al.Value of measuring serum procalcitonin,C-reactive protein,and mannan antigens to distinguish fungal from bacterial infections[J].Eur J Clin Microbiol Infect Dis,2005,24(4):272-275.
[30] Hu B,Cai K,Liu M ,et al.Laboratory detection and molecular phylogenetic analysis of severe fever with thrombocytopenia syndrome virus in Hubei Province,central China[J].Arch Virol,2018,163(12):3243-3254.
[2] 国家老年疾病临床医学研究中心(解放军总医院),《感染诱发的老年多器官功能障碍综合征诊治中国专家共识》撰写组,边素艳,等.感染诱发的老年多器官功能障碍综合征诊治中国专家共识[J].中华老年多器官疾病杂志,2018,17(1):3-15.
[3] 吴骎,任建安.外科感染合并血小板减少诊治进展[J].中国实用外科杂志,2016,36(2):241-244.
[4] 崔小波,王定芳.新型布尼亚病毒感染致发热伴血小板减少综合征1例报告[J].中国病原生物学杂志,2011,6(9):720.
[5] 郭宏岗,沈建良.93例血小板减少症的病因分析[J].中外医疗,2016,35(21):45-48.
[6] Wasserkrug Naor A ,Lindemann DM ,Schreeg ME,et al.Clinical,morphological,and molecular characterization of an undetermined Babesia species in a maned wolf (Chrysocyon brachyurus)[J].Ticks Tick Borne Dis,2019,10(1):124-126.
[7] Tagami T,Matsui H,Fushimi K,et al.Intravenous immunoglobulin and mortality in pneumonia patients with septic shock:an observational nationwide study[J].Clin Infect Dis,2015,61(3):385-392.
[8] 孙建,吴伟东.脓毒症相关性血小板减少症的危险因素及预后分析[J].中华危重症医学杂志(电子版),2014,7(3):177-181.
[9] 吴安华,李春辉.重症感染的诊断与治疗 [J] .中华急诊医学杂志,2011,20(3):334-336.
[10] 中华医学会重症医学分会.中国严重脓毒症/脓毒性休克治疗指南(2014) [J] .中华内科杂志,2015,54(6):557-581.
[11] Qi L,Fan W,Xia X,et al.Nosocomial outbreak of Candida parapsilosis sensustricto fungaemia in a neonatal intensive care unit in China[J].J Hosp Infect,2018,100(4):e246-e252.
[12] Nishio Y ,Kawano Y,Kawada JI,et al.A case of refractory cytomegalovirus-related thrombocytopenia that achieved complete remission without antiviral therapy[J].J Infect Chemother,2018,24(12):995-997.
[13] 孔海平,吴小花.肠道病毒感染伴血小板减少症新生儿的护理[J].中国现代药物应用,2012,6(9):110-111.
[14] Stearns V,Brufsky AM ,Verma S,et al.Expanded-access study of palbociclib in combination with letrozole for treatment of postmenopausal women with hormone receptor-positive,HER2-negative advanced breast cancer[J].Clin Breast Cancer,2018,18(6):e1239-e1245.
[15] Karnisova L,Hradsky O ,Blahova K,et al.Complement activation is associated with more severe course of diarrhea-associated hemolyticuremic syndrome,a preliminary study[J].Eur J Pediatr,2018,177(12):1837-1844.
[16] Fajgenbaum DC.Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease[J].Blood,2018,132(22):2323-2330.
[17] 韩常新,孙艾军,蒲春文,等.新型布尼亚病毒感染致发热伴血小板减少综合征的流行病学特征及预后影响指标分析[J].中华医院感染学杂志,2019,29(2):171-174.
[18] Soares MO,Welton NJ,Harrison DA,et al.Intravenous immunoglobulin for severe sepsis and septic shock:clinical effectiveness,cost-effectiveness and value of a further randomised controlled trial[J].Crit Care,2014,18(6):649.
[19] Mancini N,Sambri V,Corti C,et al.Cost-effectiveness of blood culture and a multiplex real-time PCR in hematological patients with suspected sepsis:an observational propensity score-matched study[J].Expert Rev Mol Diagn,2014,14(5):623-632.
[20] Rimmer E,Kumar A,Doucette S,et al.Activated protein C and septic shock:a propensity-matched cohort study*[J].Crit Care Med,2012,40(11):2974-2981.
[21] Scriven JE ,Scobie A ,Verlander NQ,et al.Mycobacterium chimaera infection following cardiac surgery in the United Kingdom:clinical features and outcome of the first 30 cases[J].Clin Microbiol Infect,2018,24(11):1164-1170.
[22] Amer A,Kaidar M,Tasher D,et al.Epstein-Barr virus infection was associated with nephrotic syndrome,severe thrombocytopenia and coombs-positive haemolytic anaemia[J].Arch Dis Child,2018,107(11):2030-2031.
[23] 陶文元,陶欣.新型布尼亚病毒感染致发热伴血小板减少综合8例报告[J].江苏大学学报(医学版),2011,21(1):91-92.
[24] Schubert J,Weissbrich B.Detection of virus-specific intrathecally synthesised immunoglobulin G with a fully automated enzyme immunoassay system[J].BMC Neurology,2007,7(1):12-16.
[25] Miroslav Pohanka.Monoclonal and polyclonal antibodies production - preparation of potent biorecognition element[J].J Appl Biomed,2009,7(3):115.
[26] Fesel C,Goulart LF,Silva Neto A,et al.Increased polyclonal immunoglobulin reactivity toward human and bacterial proteins is associated with clinical protection in human Plasmodium infection[J].Malar J,2005,4(1):5-12.
[27] Djordjevic D,Pejovic J,Surbatovic M,et al.Prognostic value and daily trend of interleukin-6,neutrophil CD64 expression,C-reactive protein and lipopolysaccharide-binding protein in critically ill patients:reliable predictors of outcome or not?[J].J Med Biochem,2015,34(4):431-439.
[28] Barie PS,Hydo LJ,Shou J,et al.Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection[J].Surg Infect (Larchmt),2005,2005,6:41-54.
[29] Petrikkos GL,Christofilopoulou SA,Tentolouris NK,et al.Value of measuring serum procalcitonin,C-reactive protein,and mannan antigens to distinguish fungal from bacterial infections[J].Eur J Clin Microbiol Infect Dis,2005,24(4):272-275.
[30] Hu B,Cai K,Liu M ,et al.Laboratory detection and molecular phylogenetic analysis of severe fever with thrombocytopenia syndrome virus in Hubei Province,central China[J].Arch Virol,2018,163(12):3243-3254.
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