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脓毒症诊治调查及玻连蛋白与脓毒症的相关性

The Diagnosis and Treatment of Sepsis and the Correlation between Vitronectin and Sepsis

【作者】 张春丽

【导师】 陈娜; 李伟;

【作者基本信息】 河南大学 , 临床医学(专业学位), 2019, 硕士

【摘要】 背景:sepsis3.0表明脓毒症是由感染引起的宿主反应平衡的失调,导致的危及生命的器官功能障碍[2]。全球每年脓毒症的新诊断占各种疾病的首位,达3100万,而且发病率正持续增长[1]。脓毒症的高发病率、高死亡率、高医疗费用,对人类健康造成了严重的威胁。脓毒症定义和诊断标准历经更新,反映了脓毒症的复杂性及医护人员对其做出的努力。但全球脓毒症的诊治现状仍不容乐观。不同地区脓毒症的患病人口、发病率、病死率等特点均有差异。脓毒症流行病学对国家医疗政策,医疗资源配置和科研方向的确定有重要意义,但国内却少有研究。河南省是人口大省,在该领域迄今无相关研究资料。因此我们依托河南大学淮河医院脓毒症实验室开始相关研究。本论文的第一部分统计了2016-06至2018-08河南大学淮河医院脓毒症流行病学特征及其诊治现状,该部分研究结果将为预防及控制脓毒症病情提供理论依据,并指导临床救治及对患者预后进行评估。脓毒症的一个重要病理变化是弥漫性血管内凝血(Diffuse Intravascular Coagulation,DIC)以及凝血功能障碍。血浆中玻连蛋白(vitronectin,VTN)含量可达400mg/L,参与凝血的过程,但其是否参与脓毒症的病理生理过程尚无文献报道。我们既往研究发现脓毒症患者血浆中VTN水平降低。因此我们设想VTN可能在脓毒症及脓毒症凝血功能障碍的发病过程中具有重要的作用,在血浆中VTN主要有两种亚型,其分子量不同,分别为75KD、65KD。因此我们进一步分析VTN不同亚型与脓毒症及脓毒症凝血功能障碍的凝血功能临床指标之间的关系。该部分研究成果将有助于阐明VTN在脓毒症发病机制的作用以及脓毒症治疗方法的设计。方法:1.根据sepsis3.0诊断标准,选择2016-06至2018-08河南大学淮河医院RICU 154例脓毒症患者及全院住院患者作为研究对象,并记录其姓名、性别、年龄等相关信息,通过(成电医星病案管理系统,2012)以“脓毒症、脓毒血症、脓毒性休克、多脏器功能障碍、感染性休克、全身炎症反应”为关键词对2016-06至2018-08期间RICU及全院诊断为脓毒症的患者进行检索,并通过该信息系统检索河南大学淮河医院呼吸科2016-06至2018-08期间入院病人及死亡病人病例数;并对性别、年龄、sofa评分、器官功能障碍数目,诊断率、病死率、存活率等流行病学指标进行分析。2.选取2016-06至2018-08入住河南大学淮河医院RICU合并肺炎的脓毒症患者血浆标本做为研究对象。筛选脓毒症凝血功能障碍患者,同时收集社区获得性肺炎患者和正常健康人血浆标本,应用蛋白免疫印迹法测定标本中VTN及其亚型的水平,结合患者临床资料使用SPSS软件进行相关性分析。结果:1.脓毒症流行病学调查结果:(1)河南大学淮河医院全院病人的死亡率为7‰,呼吸科为11‰,RICU为109‰,脓毒症患者为348‰。(2)通过计算机检索得出RICU脓毒症患者为29人,男性48.3%,女性51.7%。根据sepsis3.0诊断标准进行人工筛选出154人,男性73.4%,女性26.6%。计算机检索覆盖率18.83%,误差率81.17%。因此计算机检索全院脓毒症患者185人,男性54%,女性46%。以RICU计算机检索覆盖率校正后,全院患者约982人。(3)人工筛选脓毒症患者最小年龄24岁,最大年龄94岁,中位数71。(4)RICU脓毒症患者入院时sofa评分1-4分21.4%,5-8分42.8%,9-12分25.3%,13-16分9.74%,大于16分0.6%。入院后10%发展为脓毒症,绝大多数患者(90%)有两种以上系统功能障碍,发生率依次为呼吸、凝血、神经、代谢、肾脏、心血管和肝脏,脓毒性休克34%。(5)2016-2018年度河南大学淮河医院RICU脓毒症患者入院平均sofa评分无显著区别,存活率分别为37.5%、40.28%和46.51%。2.VTN及不同亚型的研究结果:(1)社区获得性肺炎患者血浆中VTN水平较正常健康人无明显区别。(2)脓毒症及脓毒症凝血功能障碍患者血浆标本中VTN水平明显低于正常健康人及社区获得性肺炎患者。(3)VTN水平与脓毒症凝血功能障碍患者PTA具有显著相关性p<0.05(4)VTN分子量75KD亚型水平与脓毒症凝血功能障碍患者PTA具有显著相关性p<0.05(5)VTN分子量65KD亚型水平与脓毒症凝血功能障碍患者PTA无明显相关性p>0.05结论:1.脓毒症流行病学结论:(1)脓毒症患者误诊率极高。(2)RICU脓毒症患者病死率高于发达国家和国内经济发达中心城市,呈逐年降低趋势。(3)脓毒症的预后与年龄、入院病情、sofa评分和功能障碍器官的数量负相关。2.VTN及不同亚型相关分析结论:(1)脓毒症及脓毒症凝血功能障碍患者血浆VTN水平降低。(2)VTN在脓毒症凝血功能障碍中发挥重要的作用,不同亚型其功能不同。

【Abstract】 Background:Sepsis3.0 defines sepsis as a fatal organ dysfunction caused by dysregulated host responses triggered by infection[2].Studies have shown that the global incidence of sepsis is the highest among various diseases,more than 31million annually,and its incidence is increasing[1].The high incidence,high mortality,and high medical costs of sepsis pose a serious threat to human health.The definition and diagnostic criteria for sepsis have been updated several times,which reflects the complexity of sepsis and the efforts in its diagnoseis and treatment.However,the status of sepsis diagnosis condition of sepsis in the world is still not optimistic.There are significant-variabilities in the affected population,morbidity and mortality of sepsis in different regions.Although epidedmiological information of sepsis is very important for the determination of national medical policies,medical resource allocation,and research planning,only a few relevant studies on sepsis epidemiology in china have been conducted.Up to now,there is no relevant research data about Henan Province,which is densely populated.Therefore,we in itiated sepsis epidemonligy study of Henan Province by taking advantage of the expertise of researchers in the Sepsis Laboratory of Huaihe Hospital of Henan University.In the first part of this thesis,statistical analysis of epidemiological characteristics and the status of sepsis diagnosis and treatment in Huaihe Hospital of Henan University from 2016-06 to 2018-08 are carried out.The results of this study will provid theoretical basis for prevention and control of sepsis,and guid sepsis treatment and prognosis evaluation.An important pathological change in sepsis is DIC and coagulopathy.Vitronectin(VTN)exists in plasma at a concentration of about 400mg/L,and is involved in the process of blood coagulation,But whether it participates in the pathological process of sepsis has not been reported.Our study found that plasma VTN levels in patients with sepsis were significantly lower than healthy people and patients with community-acquired pneumonia.There is a significant correlation between VTN levels in plasma and clinical parameters related to blood coagulation in patients with septic coagulopathy,suggesting that VTN may play an important role in septic coagulopathy.There are two main subtypes of VTN in plasma,and their molecular weights are different,at around 75KD and 65KD respectively.Therefore,we further analyzed the relationship between different subtypes of VTN and clinical indicators of coagulation function in sepsis patients.The results of this part of the study will help elucidate the role of VTN in the pathogenesis of sepsis and the design of treatments for sepsis.Methods:1.According to the diagnostic criteria of sepsis 3.0,154 hospitalized sepsis patients from the RICU of Huaihe Hospital of Henan University from 2016-06 to 2018-08 were identified and selected as the research subjects,and their gender,age as well as other related information were recorded."Sepsis,septicopyemia,septic shock,multiple organ dysfunction,infectious shock,systemic inflammatory response"were input as key words in"Cheng dian Medical Star Case Management System,2012"to search RICU and patients diagnosed with sepsis in the hospital from 2016-06 to 2018-08,and the number of patients admitted and died in the Department of Respiratory Medicine of Huaihe Hospital of Henan University from 2016-06 to 2018-08 was retrieved through the computer system,and the epidemiological indicators such as gender,age,sofa score,number of organ dysfunction,diagnosis rate,mortality rate,and survival rate were also analyzed.2.The plasma samples of sepsis patients who were admitted to RICU of Huaihe Hospital of Henan University from 2016-06 to 2018-08 were selected as subjects.The criteria for screening patients with septic coagulopathy are shown in Figure 5-1.Plasma samples of 17 community-acquired pneumonia patients and 19 normal healthy people were also collected.The levels of VTN and its subtypes in these specimens were measured by through Western blotting,and the correlation data were analyzed by combining with clinical data using SPSS software.Results:1.Fingings of the epidemiology study:(1)The mortality rate of patients in Huaihe Hospital of Henan University was 7‰,11‰in respiratory department,109‰in RICU,and 348‰in patients with sepsis.(2)A computer search revealed 29 patients with RICU sepsis,48.3%male and 51.7%female.According to the diagnostic criteria of sepsis 3.0,154 people were manually screened,among which 73.4%were males and 26.6%were females.The computer retrieval coverage rate was 18.83%,and the error rate was 81.17%.The computer retrieved 185 patients with sepsis in the hospital,among which 54%were males and 46%were females.After RICU computer retrieval coverage correction,the hospital had about982 patients.(3)The minimum age of patients with sepsis was 24 years old,with a maximum age of 94 years and a median of 71.(4)Patients with RICU sepsis having a score of 1-4 points account for 21.4%,5-8 points 42.8%,9-12points 25.3%,13-16 points 9.74%,and over 16 points 0.6%.10%of patients develop sepsis after admission.The vast majority of patients(90%)have more than two systemic dysfunctions,the incidence rates from high to low are:respiration,coagulation,nerve,metabolism,kidney,angiocarpy and liver,and the septic shock rate is 34%.(5)There was no significant difference in the average sofa scores of patients with RICU sepsis in Huaihe Hospital from 2016 to 2018.The survival rates were 37.5%,40.28%and 46.51%,respectively.2.The results were obtained by VTN W-B experiment and correlation analysis:(1)The levels of VTN in plasma of patients with community acquired pneumonia were not significantly different from those of normal healthy people.(2)The VTN levels in plasma samples of patients with sepsis and sepsis coagulopathy were significantly lower than those of normal healthy people and patients with community-acquired pneumonia.(3)VTN levels were significantly correlated with PTA in patients with septic coagulopathy(p<0.05)(4)The levels of 75KD subtype of VTN correlated with PTA in patients with sepsis coagulopathy(p<0.05)(5)The levels of 65KD subtype of VTN molecular weight 65KD subtype level had no significant correlation ship with PTA in patients with septic coagulopathy.p>0.05Conclusion:1.Epidemiological conclusions of sepsis:(1)The rate of sepsis misdiagnosis is extremely high.(2)The mortality rate of patients with RICU of the Huaihe Hospital of Henan university is higher than that of developed counties and first tier Chinese cities,but is decreasing.(3)The prognosis of sepsis is inversely correlated to age,admission conditions,sofa score,and number of dysfunctional organs.2.VTN experiment and related analysis conclusions:(1)The plasma VTN levels in patients with sepsis and sepsis coagulopathy are reduced.(2)VTN may plays an important role in clotting dysfunction in sepsis,and different subtypes may have different functions.

【关键词】 脓毒症玻连蛋白凝血功能障碍流行病学
【Key words】 sepsisvitronectincoagulopathyepidemiology
  • 【网络出版投稿人】 河南大学
  • 【网络出版年期】2020年 01期
  • 【分类号】R459.7
  • 【被引频次】2
  • 【下载频次】72
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