Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

Summary. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro‐ and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not identical to the changes in patients with chronic liver disease and have not been studied in great detail. Objective: To assess thrombin generation and fibrinolytic potential in patients with ALI/ALF. Methods: We performed thrombin generation tests and clot lysis assays in platelet‐poor plasma from 50 patients with ALI/ALF. Results were compared with values obtained in plasma from 40 healthy volunteers. Results and conclusion: The thrombin generation capacity of plasma from patients with ALI/ALF sampled on the day of admission to hospital was indistinguishable from that of healthy controls, provided thrombomodulin was added to the test mixture. Fibrinolytic capacity was profoundly impaired in patients with ALI/ALF on admission (no lysis in 73.5% of patients, compared with 2.5% of the healthy controls), which was associated with decreased levels of the plasminogen and increased levels of plasminogen activator inhibitor type 1. The intact thrombin generating capacity and the hypofibrinolytic status persisted during the first week of admission. Patients with ALI/ALF have a normal thrombin generating capacity and a decreased capacity to remove fibrin clots. These results contrast with routine laboratory tests such as the PT/INR, which are by definition prolonged in patients with ALI/ALF and suggest a bleeding tendency.     

Paraquat‐induced acute kidney and liver injury: Case report of a survivor from Bangladesh

Despite high fatality following paraquat ingestion, a few percentages of patients survive even after organ damage appears. We need to focus more on careful clinical and laboratory monitoring. Early diagnosis and Supportive therapy are crucial.     

Effects of inhalable particulate matter on blood coagulation

See also Mannucci PM. Fine particulate: it matters. This issue, pp 659–61; Dales RE, Cakmak S, Vidal CB. Air pollution and hospitalization for venous thromboembolic disease in Chile. This issue, pp 669–74. Summary.  Background: Particulate matter (PM) exposure has been linked to increased risk of cardiovascular disease, possibly resulting from hypercoagulability and thrombosis. Lung and systemic inflammation resulting from PM inhalation may activate blood coagulation, but mechanisms for PM‐related hypercoagulability are still largely unknown. Objectives: To identify coagulation mechanisms activated by PM in a population with well‐characterized exposure. Methods: We measured prothrombin time (PT), activated partial thromboplastin time, endogenous thrombin potentials (ETPs) with/without exogenous triggers and with/without soluble thrombomodulin, tissue‐type plasminogen activator (t‐PA) antigen, D‐dimer and C‐reactive protein (CRP) in 37 workers in a steel production plant with well‐characterized exposure to PM with aerodynamic diameter of < 1 μm (PM₁) and coarse PM (PM₁₀ – PM₁). Blood samples were collected from each subject on the first (baseline) and last (postexposure) day of a 4‐day work week. We analyzed differences between baseline and postexposure levels using a paired Student’s t‐test. We fitted multivariate mixed‐regression models to estimate the associations of interquartile range PM₁ and coarse PM exposure with parameter levels. Results: None of the parameters showed any significant changes from baseline in postexposure samples. However, exposure levels were associated with shorter PT (β[PM₁] = ?0.33 s, P = 0.08; β[PM_coarse] = ? 0.33 s, P = 0.01), and higher ETP without exogenous triggers and with thrombomodulin (β[PM₁] = + 99 nm min, P = 0.02; β[PM_coarse] = + 66 nm min, P = 0.05), t‐PA (β[PM₁] = + 0.72 ng mL^?1, P = 0.01; β[PM_coarse] = + 0.88 ng mL^?1, P = 0.04), and CRP (β[PM₁] = + 0.59 mg L^?1, P = 0.03; β[PM_coarse] = + 0.48 mg L^?1, P = 0.01). Conclusions: PM exposure did not show any short‐term effect within the week of the study. The association of PM exposure with PT, ETP and CRP provides some evidence of long‐term effects on inflammation and coagulation.     

NGAL在肝硬化继发急性肾损伤中的临床诊断价值分析

目的探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在肝硬化继发急性肾损伤(AKI)中的诊断价值。方法选取120例肝硬化患者作为研究对象,回顾性分析其临床资料,根据是否继发AKI分为肝硬化继发AKI组(n=80)与未继发AKI组(n=40),比较两组患者血清NGAL、尿液NGAL水平。然后将肝硬化继发AKI组患者进行AKI分期,比较不同分期组患者血清NGAL、尿液NGAL水平。结果肝硬化继发AKI患者血清和尿液NGAL水平分别为(624.7±42.6)、(1.98±0.36)g/L,未继发AKI患者血清和尿液NGAL水平分别为(59.3±10.4)、(0.56±0.11)g/L,组间比较显示,肝硬化继发AKI组患者血清和尿液NGAL水平明显高于未继发AKI组患者,差异有统计学意义(P0.05)。AKI分期后,不同AKI分期组间血清和尿液NGAL水平不同(P0.05),且随着AKI分期增加,血清和尿液NGAL水平升高,组间比较差异均有统计学意义(P0.05)。结论肝硬化继发AKI患者血清和尿液NAGL水平明显高于未继发AKI者,且随着AKI分期增加其水平明显升高,可以作为肝硬化继发AKI早期诊断的有效指标。     

山莨菪碱对大鼠急性肝损伤的保护作用及其机制

目的：探讨山莨菪碱对急性肝损伤的保护作用及其作用机制。方法：雄性Ｗｉｓｔａｒ大鼠１８只随机分为３组：正常对照组、模型组和山莨菪碱组。以Ｄ半乳糖胺加内毒素脂多糖制成大鼠急性肝损伤模型。用山莨菪碱（２０ｍｇ／ｋｇ）预处理模型鼠。观察３组大鼠肝酶含量，血清一氧化氮（ＮＯ）含量，肝组织中ＮＯ、丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＳＯＤ）活性及肝组织病理学变化。结果：山莨菪碱组大鼠丙氨酸转氨酶〔ＡＬＴ（６６６±２６７）Ｕ〕、天冬氨酸转氨酶〔ＡＳＴ（１０５９±４０８）Ｕ〕及血清总胆红素〔ＴＢＩＬ（７．２２±５．６２）μｍｏｌ／Ｌ〕均明显低于模型组〔分别为（２３５２±６９８）Ｕ，（３５４９±７１７）Ｕ和（２０．７１±５．９２）μｍｏｌ／Ｌ〕，Ｐ均＜０．０１；伴随着山莨菪碱对血及肝组织中ＮＯ过量合成的抑制，肝组织中ＭＤＡ降低、ＳＯＤ增高（Ｐ均＜０．０１）。山莨菪碱组肝组织病理改变较模型组明显减轻。结论：山莨菪碱对大鼠急性肝损伤有保护作用，保护作用可能与山莨菪碱抑制ＮＯ的过量产生及清除自由基有关。     

异甘草酸镁预防急性白血病患者化疗药物性肝损害的疗效观察

目的观察异甘草酸镁预防急性白血病患者化疗药物性肝损害的疗效。方法急性白血病患者66例,随机分为2组：预防组34例,对照组32例。预防组给予化疗药物＋异甘草酸镁;对照组仅使用化疗药物。结果预防组出现肝损害有15例次（9.6%）,对照组46例次（31.7%）,2组差异有统计学意义;预防组预防肝损害有效率82.7%,对照组有效率22.7%,2组比较差异显著。治疗过程中未出现与异甘草酸镁相关不良反应。结论异甘草酸镁对急性白血病患者的化疗药物性肝损害具有较好的防治作用,值得临床推广。     

急性肝损伤大鼠肝脏Fas和FasL的表达及其意义

目的 研究急性肝损伤大鼠肝脏Fas和FasL的表达情况，探讨细胞凋亡在中毒性肝损伤发病中的地位及其意义。方法 健康雄性Wistar大鼠35只，随机分为正常对照组和实验组，实验组再分为3、9、16、24、36和48h6个亚组，每组5只。制备四氯化碳中毒性肝损伤动物模型，采用苏木素-伊红（HE）染色，光镜下观察肝组织损伤情况，采用免疫组化方法测定不同时间点肝组织Fas和FasL的表达，采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）观察肝细胞凋亡情况。同时测定各时间点血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和肝组织超氧化物歧化酶（SOD）活性、肝组织丙二醛（MDA）含量变化。结果 Fas和FasL在正常大鼠肝细胞中未见表达，实验组3h后即开始有明显表达，并随时间延长表达相应增强；病理学和TUNEL检测结果均显示肝脏有严重损伤，大量肝细胞发生凋亡。大鼠染毒后血清ALT、AST活性和肝组织MDA含量明显升高，肝组织SOD活性显著降低，与正常对照组比较差异均十分显著（P〈O．05或P〈O．01）。结论 大鼠急性肝损伤时Fas和FasL表达显著增加，和肝细胞凋亡变化相一致，提示Fas／Fasl。系统及介导的细胞凋亡反应在中毒性肝损伤的发病机制中可能占有重要地位。     

纤维支气管镜在肝移植术后急性肺损伤治疗中的应用

目的 回顾性探讨床旁纤维支气管镜(纤支镜)在肝移植术后急性肺损伤(ALI)治疗中的临床应用价值.方法 将58例肝移植术后各种原因导致的ALI患者按是否采用纤支镜干预治疗分为纤支镜治疗组(36例)和常规治疗组(22例),通过比较两组重症加强治疗病房(ICU)停留时间、机械通气时间、ALI病死率、急性呼吸窘迫综合征(ARDS)进展率及其病死率,以及纤支镜使用前后的动脉血气分析变化等,评价纤支镜治疗肝移植术后ALI的临床疗效.结果 与常规治疗组比较,纤支镜治疗组的ICU停留时间[(11±4)d比(16±4)d]、机械通气时间[(9±5)d比(14±5)d]均明显缩短(P均＜0.01),ALI病死率(11.1%比36.4%)及ARDS进展率(27.8%比54.5%)明显降低(P＜0.05和P＜0.01),而ARDS病死率无显著变化[40.0%(4/10)比66.7%(8/12),P＞0.053;纤支镜治疗后动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、动脉血氧饱和度(SaO2)及氧合指数(PaO2/FiO2)均明显好转,与治疗前比较差异均有统计学意义(P均＜0.01).结论 纤支镜是肝移植术后ALl安全、有效的治疗方法,值得推广.     

早产儿凝血功能的探讨

目的探讨早产儿凝血功能与足月新生儿凝血功能的关系。方法对该院儿科149名早产儿凝血功能状态进行回顾性分析,检测凝血酶原时间(PT)、部分活化凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)含量、血小板计数(PLT)及头颅CT,分析早产儿凝血功能的特点及发生颅内出血的概率,以及胎龄与颅内出血的相关性。结果早产儿均不同程度存在凝血功能低下情况,与足月儿比较差异有统计学意义,根据胎龄大小分组分析进行统计检验,发现胎龄越低凝血功能低下程度越严重,发生颅内出血比例越高,早产儿中发生颅内出血67例,占早产儿总数的45.0%,胎龄与早产儿颅内出血呈显著负相关(r=-0.362,P0.01)。结论早产儿的凝血功能比足月新生儿的低,凝血功能低下是早产儿常见并发症,是发生颅内出血的重要原因之一,胎龄越低凝血功能低下越严重,颅内出血发生率越高。     

ICU急性肾损伤的高危因素分析

目的：探讨ICU住院患者急性肾损伤的危险因素。方法：回顾性分析重症监护病房2008-03-2013-03住院治疗的840例患者临床资料,应用多因素回归分析方法探讨发生急性肾损伤的高危因素。结果：840例患者中284例发生AKI,发病率为33.8%。284例AKI患者死亡68例,死亡率23.9%。年龄、APACHEⅡ分值、脓毒症、糖尿病、使用肾毒性药物、基线血肌酐值、休克是AKI发生的危险因素。结论：AKI是ICU中常见并发症,死亡率高。年龄、APACHEⅡ分值、脓毒症、糖尿病、使用肾毒性药物、基线血肌酐值、休克是AKI发生的独立危险因素,应采取多种综合措施减少AKI发生。     

Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome

Summary. Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho‐alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator‐induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor‐mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator‐mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti‐inflammatory effects of these therapies in ARDS and pneumonia.     

Role of hemostatic factors in hepatic injury and disease: animal models de‐liver

Chronic liver damage is associated with unique changes in the hemostatic system. Patients with liver disease often show a precariously rebalanced hemostatic system, which is easily tipped towards bleeding or thrombotic complications by otherwise benign stimuli. In addition, some clinical studies have shown that hemostatic system components contribute to the progression of liver disease. There is a strong basic science foundation for clinical studies with this particular focus. Chronic and acute liver disease can be modeled in rodents and large animals with a variety of approaches, which span chronic exposure to toxic xenobiotics, diet‐induced obesity, and surgical intervention. These experimental approaches have now provided strong evidence that, in addition to perturbations in hemostasis caused by liver disease, elements of the hemostatic system have powerful effects on the progression of experimental liver toxicity and disease. In this review, we cover the basis of the animal models that are most often utilized to assess the impact of the hemostatic system on liver disease, and highlight the role that coagulation proteases and their targets play in experimental liver toxicity and disease, emphasizing key similarities and differences between models. The need to characterize hemostatic changes in existing animal models and to develop novel animal models recapitulating the coagulopathy of chronic liver disease is highlighted. Finally, we emphasize the continued need to translate knowledge derived from highly applicable animal models to improve our understanding of the reciprocal interaction between liver disease and the hemostatic system in patients.     

急性上消化道出血并发急性心肌损伤的危险因素分析

目的:分析急性上消化道出血患者并发急性心肌损伤患者的临床特点,探讨其发生急性心肌损伤的危险因素.方法:收集我院2019年1月1日-2020年8月31日期间急诊就诊的226例老年上消化道出血患者的临床病例资料,其中男166例,女60例;分为急性心肌损伤组70例和无急性心肌损伤组156例.比较2组患者的临床指标差异,获得其...     

肝移植急性肺损伤患者围手术期血清细胞因子的比较蛋白组学分析

目的 分析肝移植围手术期急性肺损伤(ALI)的细胞因子表达特点,以期为筛选肝移植ALI的早期标志物和早期治疗靶点奠定基础.方法 乙型肝炎肝硬化行同种异体原位肝移植术后发生ALI男性患者4例,术前无肺、肾、脑等重要脏器异常,术中尿量、出血量、腹水量、血制品输入量、手术时间、无肝期时间及血管活性药物用量、利尿药使用情况及循环情况等差异无统计学意义.采集麻醉后、新肝3 h、新肝24 h的血清,利用RayBioR人抗体芯片试剂盒分析细胞因子的表达特点.结果 与健康者比较,肝移植ALI患者在麻醉后就已有部分细胞因子表达增强,包括白细胞介素(IL-3、IL-6、IL-12 p40、IL-12 p70)、单核细胞趋化蛋白2(MCP-2)、巨噬细胞集落刺激因子(M-CSF)、r-干扰素诱导单核因子(MIG)、巨噬细胞炎性蛋白-1a(MIP-1a)、可溶性肿瘤坏死因子受体I(sTNFR I),其中尤以sTNFR Ⅱ表达上调的幅度大,正常T细胞表达和分泌因子(RANTES)、血小板衍化生长因子-BB(PDGF-BB)表达明显下调.在新肝3 h时表达上调的细胞因子种类有所增加,其中尤以IL-12 p70、sTNFR I、sTNFRⅡ表达上调的幅度较大;RANTES、PDGF-BB、IL-1a表达明显下调.在新肝24 h时表达上调的细胞因子种类和程度大幅增加.与新肝3 h相比,新肝24 h嗜酸粒细胞选择性趋化因子(eotaxin)、IL-1a、IL-1β、IL-4、IL-15、MCP-2表达明显上调,IL-3、IL-6表达上调的幅度大,IL-2表达上调幅度最大.结论 在麻醉后、新肝3 h、新肝24 h分别有不同的炎症因子表达减弱或增强,且表达增强的幅度不同,某些因子的变化可能是重要的早期标志物和治疗靶点,提示需要进行大样本研究.     

复方丹参对急性肺损伤患者血小板活化因子表达及凝血功能的影响

目的 探讨复方丹参注射液对急性肺损伤(ALI)患者血清血小板活化因子(PAF)表达及凝血系统功能的影响.方法 ALI患者40例,随机分为对照组和治疗组,每组各20例,对照组予以治疗原发病、机械通气、激素治疗、抗感染、维持水电解质及酸碱平衡等常规治疗.治疗组在常规治疗的基础上加用复方丹参注射液20 mL溶于5%葡萄糖注射液250 mL中静脉滴注,1次/d,共3 d.分别于治疗前及治疗3 d后测定血清PAF、血栓素B_2(TXB_2)和凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、血小板参数及血气分析.比较对照组和治疗组治疗前后血清PAF、TXB_2和PT、APTT、FIB、血小板参数及血气分析变化.结果 与治疗前比较,治疗后两组氧合均改善,PAF和TXB_2下降,PT、APTT延长,FIB下降,血小板参数改善(均P<0.01).与对照组比较,治疗组治疗后氧合显著改善,PAF和TXB_2显著下降,PT、APTT显著延长,FIB显著升高,血小板参数显著改善(P<0.01或P<0.05).但两组病死率比较差异无统计学意义(P>0.05).结论 复方丹参能减少ALI患者PAF的表达,改善ALI患者高凝状态和氧合,为临床早期治疗ALI提供了新方法.     

乙酰唑胺在大鼠脓毒症所致急性肾损伤中作用

目的探讨乙酰唑胺对脓毒症诱导大鼠急性肾损伤的影响及其抗炎机制。方法 36只雄性Wistar大鼠随机分为对照组、脂多糖(lipopolysaccharide, LPS)组和乙酰唑胺组各12只。对照组腹腔注射600μL生理盐水;LPS组腹腔注射600μL LPS;乙酰唑胺组腹腔注射乙酰唑胺800μL,连续7 d,最后1次给药后1 h,腹腔注射600μL LPS。3组分别于12、24、48、72 h时各处死3只大鼠,采用ELISA法检测大鼠血清和肾组织白细胞介素(interleukin, IL)-6、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)和诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)水平,采用全自动生化分析仪检测大鼠血清肌酐水平,并观察大鼠一般情况和肾脏组织病理学变化。结果 LPS组大鼠各时间点血清肌酐及血清和肾组织IL-6、TNF-α和iNOS水平高于对照组和乙酰唑胺组(P<0.05),乙酰唑胺组高于对照组(P<0.05),3组大鼠血清肌酐及血清和肾组织IL-6、TNF-α和iNOS水平12~24 h呈上升趋势,24~72 h呈下降趋势,24 h时达到高峰;对照组大鼠肾小管结构清晰,基底膜完整,间质未见炎症细胞浸润;LPS组大鼠肾小管上皮细胞肿胀、变性,间质和肾小管明显炎症浸润;乙酰唑胺组LPS造成的组织细胞损伤未见明显改善,但对炎症渗出有明显抑制。结论乙酰唑胺通过抑制炎性反应减轻大鼠脓毒症所致肾损伤。     

急性超容量血液稀释对高龄患者心排量及凝血功能的影响

目的探讨急性超容量血液稀释对高龄患者心排量及凝血功能的影响。方法选取大关节手术患者60例,随机分成实验组30例和对照组30例。实验组给予6%羟乙基淀粉和乳酸林格氏液15 m L/kg行AHH;对照组不行AHH,予常规补液。比较2组患者心排量及凝血功能。结果实验组患者行AHH后,心排量(CO)有所增加,凝血功能有所降低。2组各时点的CO、红细胞压积(HCT)、凝血酶原时间(PT)、部分活化凝血酶原时间(APTT)以及血浆纤维蛋白原(Fib)比较,差异均无统计学意义(P0.05)。结论急性超容量血液稀释对高龄患者心排量及凝血功能的影响较小。     

肝硬化患者继发急性肾损伤的实验室评价

目的探讨中性粒细胞相关载脂蛋白(NGAL)、半胱氨酸蛋白酶抑制剂C(CysC)和肌酐(Cr)检测在肝硬化患者继发急性肾损伤(AKI)中的应用价值。方法选取2015年1月至2016年8月绵阳市中心医院符合入选标准的肝硬化继发AKI患者207例(AKI组)、单纯肝硬化患者260例(LC组)和健康者106例(HC组),统计分析3组及不同分期AKI患者血清NGAL(sNGAL)、尿NGAL(uNGAL)、血清CysC和血清Cr(sCr)及其估算肾小球滤过率(eGFR:CysC-eGFR/c-aGFR)水平的差异性和相关性,并评估其对肝硬化继发AKI的诊断性能。结果 AKI组sNGAL、uNGAL、CysC和sCr水平高于LC组和HC组(P0.01),CysC-eGFR和c-aGFR则相反,低于LC组和HC组(P0.01)。随着AKI分期递增,患者sNGAL、uNGAL、CysC和sCr水平逐渐升高(P0.01),c-aGFR和CysC-eGFR水平逐渐降低(P0.01)。相关分析显示,sNGAL、uNGAL和CysC水平与sCr(r=0.662、0.672、0.726,P0.01)呈正相关,与c-aGFR(r=-0.639、-0.661、-0.732,P0.01)呈负相关;CysC-eGFR则反之,与sCr(r=-0.711,P0.01)呈负相关,与c-aGFR(r=0.736,P0.01)呈正相关。ROC曲线分析显示曲线下面积(AUC)以uNGAL最大(0.995),均显著高于sNGAL、sCr、CysC、c-aGFR和CysC-eGFR(P均0.01);sNGAL的AUC次之,但仅高于c-aGFR和CysC-eGFR(P均0.05),与sCr和CysC(P均0.05)的AUC差异无统计学意义。uNGAL和sNGAL对肝硬化继发AKI的诊断有效性分别为0.962和0.920。结论对诊断肝硬化患者发生AKI,NGAL可能优于sCr和CysC,检测uNGAL比sNGAL能提高诊断性能。