Successful treatment of drug‐induced acute liver failure with high‐volume plasma exchange

We report two patients with drug‐induced liver injury (DILI)‐related acute liver failure (ALF) who were successfully treated with high‐volume plasma exchange without liver transplantation. The first patient was a 66‐year‐old man admitted because of a perforated duodenal ulcer complicated with peritonitis and septic shock. After treatment with multiple antibiotics, the patient developed DILI and ALF. Grade 3 hepatic encephalopathy and profound jaundice were present. Symptoms and signs of ALF improved dramatically after initiation of plasma exchange. The patient was discharged uneventfully. The second patient was a 94‐year‐old man admitted for treatment of newly diagnosed pulmonary tuberculosis. DILI and ALF developed 5 days after initiation of anti‐tuberculosis treatment. Grade 4 hepatic encephalopathy was present. After plasma exchange, the patient's level of consciousness improved dramatically, and he recovered from ALF. These 2 cases show the potential of plasma exchange in the treatment of DILI despite occurrence acute liver failure. J. Clin. Apheresis, 28:430–434, 2013. © 2013 Wiley Periodicals, Inc.     

TECAI型生物人工肝支持系统治疗急性肝衰竭犬的实验研究

目的评价经改进的TECAI型生物人工肝脏支持系统（bioartificial liver supportsyst em,BALSS）治疗醋氨酚诱发急性肝衰竭(acute liver failure,ALF)犬的有效性和安全性。方法采用多次皮下注射醋氨酚的方法建立ALF模型犬。分离中国实验用小型猪肝细胞并培养于BALSS中,对ALF犬进行6小时的治疗,观察治疗前后犬生理、生化和组织学的变化,与常规药物治疗组和对照组进行比较。结果注射醋氨酚48小时后,可建立ALF犬模型,模型成功率为63.16%。应用我们改进的酶消化法,平均从每只小型猪的肝脏可得到（0.8～3.0）×10     

Effects of acute liver injury on blood coagulation

Summary.  The mechanisms leading to the hemostatic changes of acute liver injury are poorly understood. To study these further we have assessed coagulation and immune changes in patients with acute paracetamol overdose and compared the results to patients with chronic cirrhosis and normal healthy controls. The results demonstrate that in paracetamol overdose coagulation factors (F)II, V, VII and X were reduced to a similar degree and were significantly lower than FIX and FXI (mean levels 0.28, 0.16, 0.13, 0.19, 0.51 and 0.72 IU mL⁻¹, respectively). In cirrhosis, by contrast, FII, FV, FVII, FIX and FX were equally reduced whilst FXI was lower than the other factors (mean levels 0.64, 0.69, 0.62, 0.60, 0.66 and 0.40 IU mL⁻¹, respectively). FVIII was raised in paracetamol overdose patients but normal in those with cirrhosis (mean levels 1.95 and 1.01 IU mL⁻¹, respectively). Interleukin-6 and tumor necrosis factor-α levels were raised in both patient groups, but higher levels were found in paracetamol overdose, compared to cirrhosis. Thrombin-antithrombin and soluble tissue factor levels were higher in those with acute liver injury but normal in cirrhosis. Antithrombin levels were reduced in both acute liver injury and cirrhosis. From these data we put forward a novel mechanism for the coagulation changes in acute paracetamol induced liver injury. We propose that immune activation leads to tissue factor-initiated consumption of FII, FV, FVII and FX, but that levels of FIX and FXI are better preserved because antithrombin inhibits the thrombin induced positive feedback loop that activates these latter factors.     

儿童急性肝衰竭的诊疗进展

急性肝衰竭（acute liver failure,ALF）是一种严重的累及多个系统的临床综合征,在短时间内出现严重的肝功能损伤,并有脑水肿、肝性脑病、多器官衰竭等并发症的出现,病死率极高。ALF在儿童中的确切发生率还不清楚,在需要肝移植的儿童患者中,ALF的患者占10％～15％。对儿童ALF的诊断和治疗,缺乏大规模、多中心的临床研究。目前儿童ALF的诊疗方案,主要来源于成人ALF的经验。但是,儿童ALF的病因、临床特点、发病机制等都有别于成人ALF,因此有必要对儿童ALF进行专门的探讨。本文就儿童ALF的诊疗进展作一综述。     

Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension

OBJECTIVES: The present study was designed to (a) evaluate and compare plasma ammonia levels (PAL) in patients with acute liver failure (ALF) and chronic liver disease (CLD) with or without hepatic encephalopathy (HE); (b) correlate the severity of HE with PAL; and (c) correlate PAL with clinical features of raised intracranial tension in ALF. DESIGN AND METHODS: A total of 40 patients, comprised of 20 patients with ALF (Group A) and 20 patients with CLD (Group B, which was comprised of 8 patients with HE (subgroup B1) and 12 patients without HE (subgroup B2)), were studied. PAL was estimated using an enzymatic UV-method (RANDOX). The clinical and biochemical profile of all the patients was recorded. Correlation between the grade of HE and PAL was derived using Pearson's correlation coefficient. The mean PAL of ALF patients with and without raised intracranial tension was compared using the standard error of difference between the two means. RESULTS: The mean PAL (micromol/L) +/- SD was as follows: Group A: 172.1 +/- 52.55, subgroup B1: 58.75 +/- 29.38, subgroup B2: 42.17 +/- 18.19 (normal levels = 10-47 micromol/L). All patients with ALF showed PAL more than the upper limit of the normal range, and there was good correlation between the severity of HE and PAL [r = 0.91 at P < 0.05]. In subgroup B1 (CLD with HE), 3/8 patients (37.5%), and in subgroup B2 (CLD with HE), 4/12 patients (33.3%) patients had PAL more than the upper limit of normal range. Within Group A, 14 patients had clinical features of raised intracranial tension/cerebral edema, and the mean PAL of these patients (188.21 +/- 49.15 micromol/L) was significantly higher than those who did not have features of raised intracranial tension (134.5 +/- 42.36 micromol/L) (SE of difference between two means). CONCLUSIONS: Raised PAL appears to be an important laboratory abnormality seen in patients with ALF, and there seems to be a significant correlation between the severity of encephalopathy and PAL in these patients. However, among patients with CLD, the proportion of patients with PAL more than the upper limit of normal range is not significantly different between those with or without HE. Our study also suggests that high PAL in ALF patients appears to correlate with clinical features of cerebral edema and raised intracranial tension.     

Serial changes of liver stiffness measured by acoustic radiation force impulse imaging in acute liver failure: a case report

Acoustic radiation force impulse (ARFI) imaging is a new technology used to determine liver elasticity. We report the case of a patient that survived hyperacute-type acute liver failure (ALF) and who showed a dramatic change in the value of shear wave velocity (SWV) measured by ARFI, which corresponded with the severity of her liver damage. The value of SWV increased significantly up to 3.6 ± 0.3 m/s during the encephalopathy phase and then decreased along with the recovery of liver function, the blood flow of the right portal vein, and the liver volume. These findings suggest the value of SWV in ALF as a reliable marker of liver tissue damage. Further investigations of the pathophysiological significance of SWV in ALF are warranted.     

Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure

Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects ( P  < 0.01). This defect persisted when zymosan opsonized by control serum was used ( P  < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects ( P  < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor.     

Prognostic factors and treatment effect of standard-volume plasma exchange for acute and acute-on-chronic liver failure: A single-center retrospective study

Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n?=?45) and ALF (n?=?10) who received standard-volume PE (1–1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P?=?0.008), post-PE hemoglobin (P?=?0.039), and post-PE CLIF-C ACLF scores (P?=?0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve?=?0.719, P?=?0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.     

Quality of life following emergency liver transplantation for acute liver failure

INTRODUCTION: Liver transplantation is an accepted and successful therapy for both acute and chronic liver diseases (CLDs), with good survival outcomes. Whilst the study of health-related quality of life (HRQoL) post transplantation for CLDs have been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF) patients. PATIENTS AND METHODS: Data were collected using between-method triangulation; however, only the quantitative element of the study is reported here. Measuring eight health domains, we distributed the short form 36 (SF-36) questionnaire by post to 96 acute and chronic transplant recipients. Differences between the groups were measured using both parametric and non-parametric t-tests. RESULTS: Overall, the patients showed a satisfactory HRQoL; there were no differences between either acute or chronic transplant groups in seven of the eight domains of quality of life. Among the patients transplanted for ALF, there were no differences in HRQoL between patients transplanted for paracetamol hepatotoxicity compared with other indications, and no variations in HRQoL related to recipient gender, employment or length of survival post transplantation. When compared with the UK SF-36 normal values to the ALF transplant recipients, there was a significantly lower physical functioning and role emotional scores. CONCLUSION: Regardless of aetiology, most of recipients transplanted for ALF have a HRQoL comparable with chronic transplant recipients.     

The hypotaurine-taurine pathway as an antioxidative mechanism in patients with acute liver failure

The liver has been thought to protect against oxidative stress through mechanisms involving reduced glutathione (GSH) that consumes high-energy phosphor-nucleotides on its synthesis. However, hepatoprotective mechanisms in acute liver failure (ALF) where the phosphor-nucleotides are decreased in remain to be solved. Liver tissues were collected from patients with ALF and liver cirrhosis (LC) and living donors (HD) who had undergone liver transplantation. Tissues were used for metabolomic analyses to determine metabolites belonging to the central carbon metabolism, and to determine sulfur-containing metabolites. ALF and LC exhibited a significant decline in metabolites of glycolysis and pentose phosphate pathways and high-energy phosphor-nucleotides such as adenosine triphosphate as compared with HD. Conversely, methionine, S-adenosyl-l-methionine, and the ratio of serine to 3-phosphoglycerate were elevated significantly in ALF as compared with LC and HD, suggesting a metabolic boost from glycolysis towards trans-sulfuration. Notably in ALF, the increases in hypotaurine (HTU) + taurine (TU) coincided with decreases in the total amounts of reduced and oxidized glutathione (GSH + 2GSSG). Plasma NH₃ levels correlated with the ratio of HTU + TU to GSH + 2GSSG. Increased tissue levels of HTU + TU vs total glutathione appear to serve as a biomarker correlating with hyperammonemia, suggesting putative roles of the HTU-TU pathway in anti-oxidative protective mechanisms.     

纤溶酶原激活物抑制物-1与急性脑梗死并发急性肺损伤/急性呼吸窘迫综合征的相关性研究

目的探讨急性脑梗死并发急性肺损伤/急性呼吸窘迫综合征患者血清纤溶酶原激活物抑制物-1(PAI-1)水平变化及临床意义。方法采用前瞻性研究方法,收集急性脑梗死并发ALI/ARDS患者28例,单纯ALI/ARDS患者26例,健康对照组20例。根据脑梗死部位不同,A组被进一步分为前循环区组(5例)、后循环区组(15例)、分水岭区组(8例)。所有研究对象均已行头颅CT/MRI检查。A、B组行APACHEⅡ评分。检测所有患者血清PAI-1水平,比较各组PAI-1水平变化及其与A-PACHEⅡ评分相关性。结果脑梗死并发ALI/ARDS组、单纯ALI/ARDS组PAI-1水平高于对照组(P<0.01),脑梗死并发ALI/ARDS组高于单纯ALI/ARDS组(P<0.05)。后循环梗死患者ALI/ARDS发生率最高(53.57%)。血清PAI-1水平与A-PACHEⅡ评分呈正相关(P<0.01)。结论 ALI/ARDS存在凝血纤溶功能障碍,脑梗死(尤其后循环区梗死)更易致ALI/ARDS的发生,PA-I1水平可预示疾病的严重程度。     

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.     

Successful rescue of acute liver failure and hemophagocytic lymphohistiocytosis following varicella infection: A case report and review of literature

Herein we report a case of acute liver failure (ALF) and hemophagocytic lymphohistiocytosis (HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient’s condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction (PCR) amplifications of varicella-zoster virus (VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient’s symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.     

配对血浆分离吸附联合血液滤过治疗多器官功能障碍综合征的实验及临床研究

目的探讨配对血浆分离吸附法（CPFA）联合连续性静-静脉血液滤过（CVVH）治疗多器官功能障碍综合征（MODS）伴急性肝功能衰竭（ALF）患者的临床疗效和安全性。方法应用CPFA＋CVVH技术对重症加强治疗病房（ICU）中11例MODS伴ALF患者进行38例次治疗，比较患者治疗前后的平均动脉压（MAP）、氧合指数（Pa02／FiO2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、IL-6、IL-8、肝功能、肾功能、全身炎症反应综合征（SIRS）评分、急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分及临床症状改善程度，同时观察治疗的不良反应，并进行治疗安全性评价。结果患者治疗后尿量较治疗前增多，黄疽减轻，发热、乏力、腹胀、食欲明显改善，精神好转，意识转清。治疗后MAP较治疗前上升了12mmHg（1mmHg=0．133kPa），PaO2／FiO2上升了40mmHg（P均＜0．05）；TNF-α、IL-1β、IL-6、IL-8均较治疗前明显降低（P均＜0．05），血清总胆红素、直接胆红素、血氨、血尿素氮、肌酐均明显下降（P均＜20．05）；SIRS、APACHEⅡ评分均较治疗前有不同程度的下降（P均＜0．05）。11例患者存活5例，存活率为45．5％；未发生出血、休克、过敏等并发症，患者耐受好。结论CPFA联合CVVH能有效清除炎症介质，改善MODS伴ALF患者的预后，且无明显不良反应。     

Coagulation status of critically ill patients with and without liver disease assessed using a novel thrombin generation analyzer

The liver synthesizes the majority of pro‐ and anti‐coagulant and fibrinolytic proteins, and during liver dysfunction synthesis of these proteins is reduced. The end point of conventional hemostatic tests, such as the prothrombin time (PT), occurs when only 5% of thrombin generation (TG) has taken place and is not sensitive to the effects of natural anti‐coagulants. The aim of this study was to determine whether TG in the presence of thrombomodulin (TM) provides more useful information about coagulation potential, in comparison to the PT. Analysis was performed on ST Genesia, a novel TG analyzer from Diagnostica Stago. TG was measured using STG‐Thromboscreen, a reagent containing an intermediate concentration of human tissue factor (TF) ± rabbit TM to account for anti‐coagulant protein C (PC) activity. Platelet‐poor plasma (PPP) samples were from the Intensive Care Study of Coagulopathy‐2 (ISOC‐2), which recruited patients admitted to critical care with a prolonged PT (3 seconds above the reference range). Despite a prolonged PT, 48.0% and 60.7% of patients in the liver and non‐liver groups had TG parameters within the normal range. Addition of TM reduced TG by 34.5% and 41.8% in the liver and non‐liver groups, respectively. Interestingly, fresh frozen plasma (FFP) transfusion had no impact on TG. Measurement of TG with addition of TM provides a more informative assessment of coagulation capacity and indicates that hemostasis is balanced in patients with liver disease during critical illness, despite conventional tests suggesting that bleeding risk is increased.     

The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications

Introduction: Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. Patients and methods: FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute‐on‐chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post‐treatment data were performed using paired t‐test. Results: The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 ± 9.46 mg/dL vs. 9.76 ± 7.05 mg/dL; P < 0.0001), ammonia (167.6 ± 75 mg/dL vs. 120 ± 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 ± 13.03 mg/dL vs. 8.18 ± 8.15 mg/dL; P < 0.0001), creatinine (0.54 ± 0.47 mg/dL vs. 0.46 ± 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 ± 0.05 vs. 7.44 ± 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. Conclusions: FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment. J. Clin. Apheresis 25:195–201, 2010. © 2010 Wiley‐Liss, Inc.     

Caspase-cleaved cytokeratin 18 and 20 S proteasome in liver degeneration

Apoptosis of epithelial hepatocytes plays a pivotal role in acute as well as in chronic liver diseases. The cleavage of cytokeratin-18 (CK-18) by caspases is an early event in the apoptotic process. We therefore sought to investigate serum levels of CK-18 and 20S proteasome in patients with liver cirrhosis, primary graft dysfunction (PDF), and acute liver failure (ALF), and in healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the concentration of M30, a fragment of CK-18 cleaved at Asp396 (M30 neoantigen), and the concentration of 20S proteasome. Serum levels of the CK-18 neoepitope M30 were significantly increased in ALF, primary graft dysfunction, and liver cirrhosis vs. healthy controls (1,993.6+/-124.7 U/L, 2,238.1+/-235.9 U/L, and 673.6+/-86.5 U/L vs. 66.8+/-29.1 U/L, respectively, P<0.001). Similar results were detected with the evaluation of 20S proteasome (124,014.5+/-13,235.6 ng/mL, 76,993.2+/-15,720.1 ng/mL, and 2,395.9+/-1,098.2 ng/mL vs. 1,074.5+/-259.4 ng/mL, respectively; P<0.001). Detection of CK-18 neoepitope M30 and 20S proteasome may represent a novel marker of tracing apoptotic epithelium, respectively mirroring degenerative liver processes in affected patient population.     

Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia--a review

OBJECTIVES: To review the involvement of coagulation and fibrinolysis in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), pulmonary infection, and ventilator-induced lung injury (VILI). DATA SOURCE: Published articles on experimental and clinical studies of coagulation and fibrinolysis in ALI/ARDS, pneumonia, and mechanical ventilation. CONCLUSIONS: Alveolar fibrin deposition is an important feature of ALI/ARDS and pulmonary infection. The mechanisms that contribute to disturbed alveolar fibrin turnover are localized tissue factor-mediated thrombin generation and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. These effects on pulmonary coagulation and fibrinolysis are regulated by various proinflammatory cytokines and are similar to those found in the intravascular spaces during severe systemic inflammation. Some studies also suggest that pulmonary coagulopathy is a feature of VILI. Recent studies have demonstrated the beneficial effect of anticoagulant therapy in sepsis. Theoretical considerations suggest that this anticoagulant therapy will benefit patients with primary lung pathology including VILI, but clinical studies are needed to examine this hypothesis before such therapy is to be advocated as a standard of care in critically ill patients.     

Factor XII-dependent increases in thrombin activity induce carboxypeptidase-mediated attenuation of pharmacological fibrinolysis

Summary.  Activation of the contact system in patients treated with fibrinolytic agents may be an important source of thrombin that activates thrombin-activated fibrinolysis inhibitor (TAFI) and attenuates fibrinolysis. Factor (F)XIIa in plasma increased 2-fold over 60 min in patients given either tissue plasminogen activator (t-PA) or streptokinase (SK). To determine whether FXIIa-mediated generation of thrombin and activated TAFI (TAFIa) attenuates fibrinolysis in vitro , plasma clots were incubated with SK (250 U mL⁻¹) or t-PA (2.5 g mL⁻¹) and the rate of lysis was measured. Plasma FXIIa impaired lysis judging from marked acceleration when 2.5 µ m corn trypsin inhibitor were added (lysis increased by 172 ± 144% for SK and 40 ± 31% for t-PA vs. no inhibitor, n  = 16, P  < 0.01). Moreover, inhibition of thrombin with hirudin and TAFIa with carboxypeptidase inhibitor accelerated lysis. We conclude that activation of FXII increases thrombin generation, which promotes TAFIa-mediated attenuation of fibrinolysis.     

慢血、晚血、慢性乙型肝炎和肝硬化病人凝血、抗凝血及纤溶功能的研究

目的探讨慢血、晚血、慢性乙型肝炎和肝硬化患者的凝血、抗凝血及纤溶功能。方法收集血防站诊治的慢性、晚期血吸虫病和南昌大学第一附属医院住院的慢性乙型肝炎和肝硬化患者各50例及同期健康体检者50例作为对照组,测定和分析血浆凝血功能(PT、APTT、TT、Fg)、抗凝血功能(AT-Ⅲ、PC、PS)及纤溶功能[纤溶酶原(PLG)、D-二聚体(D-D)]。结果1、与健康对照组相比:⑴慢血组凝血功能(PT、APTT、TT、Fg)差异无显著性,抗凝血功能(AT-Ⅲ、PC、PS)差异有显著性,纤溶产物D-D水平差异有显著性而PLG无统计学差异;⑵晚血组PT、TT、Fg差异有显著性而APTT差异无显著性,抗凝血功能(AT-Ⅲ、PC、PS)和纤溶功能(PLG、D-D)差异有显著性;⑶慢性乙型肝炎和肝硬化组凝血功能、抗凝血和纤溶功能差异均有显著性;2、慢血组与晚血组比较:PT、TT差异有显著性而APTT、Fg差异无显著性,AT-Ⅲ、PC差异有显著性而PS差异无显著性,D-D、PLG差异有显著性;3、慢血组和慢性乙型肝炎组比较:凝血功能和抗凝血功能差异非常显著,纤溶功能PLG差异非常显著而D-D差异无显著性;4、晚血组和肝硬化组比较:凝血功能除TT差异无显著性外PT、APTT、Fg差异有显著性,抗凝血功能和纤溶功能差异有显著性;5、慢性乙型肝炎和肝硬化比较:TT、Fg差异无显著性而PT、APTT差异有显著性,抗凝血功能和D-D差异有显著性,PLG差异无显著性。结论慢血、晚血、慢性乙型肝炎及肝硬化患者均存在一定程度的凝血、抗凝血和纤溶功能紊乱,且凝血、抗凝血及纤溶指标的检测有助于监测慢血、晚血、慢性乙型肝炎及肝硬化患者病情的出凝血功能。