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Effects of activated protein C on coagulation and fibrinolysis in rabbits with endotoxin induced acute lung injury

Chinese Medical Journal 2008年第24期121卷 2561-2565页

作者： HE Hang-yong WANG Chen PANG Bao-sen Beijing Institute of Respiratory Medicine Beijing Chaoyang Hospital Capital Medical University Beijing 100020 China

Background Sepsis induced acute lung injury （ALI） as a common syndrome in clinical practice has a high mortality. Recombinant human activated protein C （APC） can significantly reduce the mortality of patients with severe sepsis. Several studies have implicated that APC may be protective in ALI. Methods Twenty-one rabbits were operatively prepared and randomly divided into sham, control, or APC groups （n=7 in each group）. After a tracheotomy had been performed, ALI was produced in the control and APC groups by infusion of Escherichia coil endotoxin 100 μg/kg per hour intravenously for 1 hour. The sham group received only the vehicle, infusion of 20 ml of 0.9% saline. The rabbits were studied under anesthesia for 6 hours and were ventilated with 40% oxygen. Bovine APC （25 μg·kg^-1·h^-1） was intravenously administered. The infusion was initiated half an hour post-injury and lasted for 4 hours. The animals were resuscitated with Ringer＇s lactate solution. Results In comparison with nontreatment in the control group, the infusion of APC significantly reduced the increase of thrombomodulin level （TM; control group was （0.68±0.06） ng/ml, vs APC group of （0.62±0.07） ng/ml at 6 hours, P 〈0.05）, and significantly attenuated the fall in protein S （PS; control group was （2.32±0.03） μg/ml at 2 hours, （2.24±0.06） μg/ml at 4 hours and （2.21±0.09）μg/ml at 6 hours, vs APC group （2.46±0.04） μg/ml at 2 hours, （2.40±0.05） μg/ml at 4 hours and （2.39±0.07） μg/ml at 6 hours, P 〈0.01）. In addition, APC limited the increase in plasminogen activator inhibitor-1 （PAI-1） both in plasma （control group was （0.68±0.12） ng/ml at 1 hour, （0.84±0.06） ng/ml at 2 hours, （0.87±0.08） ng/ml at 4 hours and （0.91±0.05） ng/ml at 6 hours, vs APC group （0.42±0.16） ng/ml at 1 hour, （0.43±0.04） ng/ml at 2 hours, （0.45±0.09） ng/ml at 4 hours and （0.45±0.14） ng/ml at 6 hours, P 〈0.01） and in bronchoalveolar lavage fluid （at 6 hours： sham, （1.05±0.05） ng/ml; control, （1.13±0.06） ng/ml; APC, （1.06±0.06） ng/ml; P 〈0

关键词： acute lung injury sepsis activated protein C coagulation fibrinolysis

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In vitro study of safety and co-efficiency of the transbronchial coagulation techniques

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Chinese Medical Journal 2013年第1期126卷 124-128页

作者： BAI Chong DONG Yu-chao SONG Xiao-lian HUANG Yi SHI Hui HU Zhen-li LI Qiang Department of Respiratory Medicine Changhai Hospital SecondMilitary Medical University Shanghai 200433 China Department of-Respiratory Medicine Shanghai 10th People'sHospital Tongji University School of Medicine Shanghai 200072China

Background The usual transbronchial coagulation techniques include microwave, argon plasma coagulation （APC）, electrocautery and cryotherapy. However, there are serious clinical problems in the safety of each. By analyzing the experimental data and clinical observations, we observed the variable effects of different coagulation techniques via bronchofibroscopy, to look for an optimal interventional management of luminal bronchus diseases, and evaluate the safety and the equivalent point. Methods Four kinds of coagulation techniques under bronchoscopy were performed on the fresh bronchus of healthy sheep, and the pathologic changes in all groups were observed under the microscope. The different treatment parameters were as follows： microwave 60 Wxl second, 3 seconds, 5 seconds and 40 W×1 second, 3 seconds, 5 seconds; APC 40 W×1 second, 3 seconds, 5 seconds; electrocautery 40 W×1 second, 3 seconds, 5 seconds; cryotherapy 100 Ω×60 seconds, 120 seconds. Results After treatment, ovine bronchial mucosa in all groups showed pathologic changes such as local necrosis and amotio of the mucosa lining epithelium, local submucosa coagulative necrosis or tissue defects, while inflammation in the surrounding tissue was not obvious. Under the same output power and action time, different methods had different outcomes. The damage by APC was the most superficial, microwave was the second, and electrocautery caused the worst damage. The study also found that effects of electrocautery at 40 W×3 seconds, microwave at 40 W×5 seconds or 60 W×3 seconds, APC at 40 W×5 seconds and cryotherapy at 100 Ω×120 seconds were the equivalent point conditions. The appearance included mucosa absence, partial submucosa absence, and collagen fiber coagulation in treatment areas. Conclusions Each coagulation technique has its own characteristic. It is very important to choose the appropriate power and action time of the suitable method according to the therapy requirement.

关键词： bronchoscopy coagulation microwave argon plasma coagulation electrocautery cryotherapy

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A multicenter, phase III trial of hemocoagulase Agkistrodon： hemostasis, coagulation, and safety in patients undergoing abdominal surgery

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Chinese Medical Journal 2010年第5期123卷 589-593页

作者： WEI Jun-min ZHU Ming-wei ZHANG Zhong-tao JIA Zhen-geng HE Xiao-dong WAN Yuan-lian WANG Shan XIU Dian-rong TANG Yun LI Jie XU Jing-yong ZHENG Qing-shan Department of General Surgery Beijing Hospital Beijing 100730 China Department of General Surgery Beijing Friendship Hospital Beijing 100050 China Department of General Surgery China-Japan Friendship Hospital Beijing 100029 China Department of General Surgery Peking Union Medical College Hospital Beijing 100730 China Department of General Surgery First Affiliated Hospital of Peking University Beijing 100034 China Department of Gastrointestinal Surgery Peking University People's Hospital Beijing 100044 China Department of General Surgery Third Affiliated Hospital of Peking University Beijing 100083 China Department of Gastrointestinal Surgery Chinese PLA General Hospital Beijing 100853 China Department of General Surgery Beijing Tongren Hospital Bejing 100730 China Center for Clinical Evaluation of Drugs Yijishan Anhui 241000 China

Background Hemocoagulase Agkistrodon for injection is a single component thrombin which has passed phases I and II clinical trials. The purpose of this phase III clinical trial was to evaluate the effect of Hemocoagulase Agkistrodon on hemostasis and coagulation in abdominal skin and subcutaneous incisions and to assess the safety of this agent in surgical patients. Methods This is a phase III, prospective, randomized, double-blind, and controlled multicenter clinical trial including 432 consecutive patients randomized into either a study group （injected with hemocoagulase Agkistrodon at 2 U, n=-324） or a control group （injected with hemocoagulase Atrox, n=108）. The hemostatic time, hemorrhagic volume, hemorrhagic volume per unit area, blood coagulation, and adverse events were measured and compared between the two groups. Results The mean hemostatic time in the study group was （36.8±18.7） seconds; the hemorrhagic volume was （3.77±3.93） g; and the hemorrhagic volume per unit area was （0.091±0.125） g/cm2. In the control group, the corresponding values were （38.1±19.7） seconds, （4.00±4.75） g, and （0.095±0.101） g/cm2, respectively. No significant difference in values existed between the two groups （P 〉0.05）. Blood coagulation results and hepatic and renal function were also similar between the two groups. Adverse events were reported in two cases, but were deemed non-drug-related. Conclusions Hemocoagulase Agkistrodon has good hemostatic and coagulative function and is safe for the use of arresting capillary hemorrhage that occurs while incising the abdomen during surgery.

关键词： hemocoagulase Agkistrodon incision bleeding hemostasis coagulation randomized controlled trial

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Immobilized thrombin on X-ray radiopaque polyvinyl alcohol/chitosan embolic microspheres for precise localization and topical blood coagulation

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Bioactive Materials 2021年第7期6卷 2105-2119页

作者： Xiaohong Li Xiongfa Ji Kun Chen Muhammad Wajid Ullah Basen Li Jiameng Cao Lin Xiao Jun Xiao Guang Yang Department of Biomedical Engineering College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China Department of Orthopedics Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou510080China Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China School of Biomedical Engineering Sun Yat-sen UniversityGuangzhou510006China Department of Orthopaedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Trans-catheter arterial embolization(TAE)plays an important role in treating various *** available embolic agents lack X-ray visibility and do not prevent the reflux phenomenon,thus hindering their application for TAE ***,we aim to develop a multifunctional embolic agent that combines the X-ray radiopacity with local procoagulant *** barium sulfate nanoparticles(BaSO4 NPs)were synthesized and loaded into the polyvinyl alcohol/chitosan(PVA/CS)to prepare the radiopaque BaSO4/PVA/CS microspheres(MS).Thereafter,thrombin was immobilized onto the BaSO4/PVA/CS MS to obtain the thrombin@BaSO4/PVA/CS *** prepared BaSO4/PVA/CS MS were highly spherical with diameters ranging from 100 to 300μ*** vitro CT imaging showed increased X-ray visibility of BaSO4/PVA/CS MS with the increased content of BaSO4 NPs in the PVA/CS *** biocompatibility assessments demonstrated that the MS were non-cytotoxic and possessed permissible hemolysis *** biofunctionalized thrombin@BaSO4/PVA/CS MS showed improved hemostatic capacity and facilitated hemostasis in ***,in vivo study performed on a rabbit ear embolization model confirmed the excellent X-ray radiopaque stability of the BaSO4/PVA/CS ***,both the BaSO4/PVA/CS and thrombin@BaSO4/PVA/CS MS achieved superior embolization effects with progressive ischemic necrosis on the ear tissue and induced prominent ultrastructural changes in the endothelial *** findings of this study suggest that the developed MS could act as a radiopaque and hemostatic embolic agent to improve the embolization efficiency.

关键词： BaSO_(4) Polyvinyl alcohol/chitosan Radiopacity Thrombin coagulation Embolization

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Efficacy and complications of argon plasma coagulation for hemorrhagic chronic radiation proctitis

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World Journal of Gastroenterology 2019年第13期25卷 1618-1627页

作者： Qing-Hua Zhong Zhan-Zhen Liu Zi-Xu Yuan Teng-Hui Ma Xiao-Yan Huang Huai-Ming Wang Dai-Ci Chen Jian-Ping Wang Lei Wang Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases Sun Yat-sen University Department of Colorectal Surgery the Sixth Affiliated Hospital Sun Yat-sen University Guangdong Institute of Gastroenterology

BACKGROUND Chronic radiation proctitis(CRP) is a complication which occurs in 1%-5% of patients who undergo radiotherapy for pelvic malignancies. Although a wide range of therapeutic modalities are available, there is no literature to date showing any particularly appropriate therapeutic modality for each disease stage. Argon plasma coagulation(APC) is currently recommended as the firstchoice treatment for hemorrhagic CRP, however, its indication based on longterm follow-up is still unclear. On the hypothesis that the long-term efficacy and safety of APC are not fully understood, we reviewed APC treatment for patients with hemorrhagic CRP from a single *** To assess the long-term efficacy and safety of APC for hemorrhagic *** This is a retrospective study of consecutive patients treated with APC for hemorrhagic CRP from January 2013 to October 2017. Demographics, clinical variables, and typical endoscopic features were recorded independently. Success was defined as either cessation of bleeding or only occasional traces of bloody stools with no further treatments for at least 12 mo after the last APC *** performed univariate and multivariate analyses to identify factors associated with success and risk factors for *** Forty-five patients with a median follow-up period of 24 mo(range: 12-67 mo)were enrolled. Fifteen(33.3%) patients required blood transfusion before *** treatment with APC was achieved in 31(68.9%) patients. The mean number of APC sessions was 1.3(1-3). Multivariate analysis showed that APC failure was independently associated with telangiectasias present on more than50% of the surface area [odds ratio(OR) = 6.53, 95% confidence interval(CI): 1.09-39.19, P = 0.04] and ulcerated area greater than 1 cm^2(OR = 8.15, 95%CI: 1.63-40.88, P = 0.01). Six(13.3%) patients had severe complications involving rectal fistulation. The only factor significantly associated with severe complications was ulcerated area great

关键词： Argon plasma coagulation Chronic radiation proctitis Radiation proctopathy Efficacy Safety

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Clinical Validation of Global coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 210-219页

作者： Madhumita Premkumar Rohit Mehtani Smita Divyaveer Kamal Kajal Anand VKulkarni Syed Ahmed Harmanpreet Kaur Harpreet Kaur Radhakrishna Dhiman Ajay Duseja Arka De Departments of Hepatology Postgraduate Institute of Medical Education and ResearchChandigarhIndia Nephrology Postgraduate Institute of Medical Education and ResearchChandigarhIndia Anesthesia and Intensive CarePostgraduate Institute of Medical Education and ResearchChandigarhIndia Department of Hepatology Asian Institute of GastroenterologyHyderabadIndia Medicine Postgraduate Institute of Medical Education and ResearchChandigarhIndia

Background and Aims:Patients with cirrhosis and acuteon-chronic liver failure(ACLF)may have bleeding complications and need for invasive ***-of-care(POC)coagulation tests like thromboelastography(TEG)and Sonoclot may be better for guiding patient management than the standard coagulation tests(SCTs),like prothrombin time,platelet count and international normalized ***:We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion *** assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC ***:Episodes of bleeding were seen in 45%and 28%of ACLF and cirrhosis patient,respectively(p=0.036),with the major site of bleeding being gastrointestinal(31%and 16%,respectively).Platelet counts correlated with TEG-maximum amplitude in cirrhosis(p=0.045)and prothrombin time correlated positively with TEG-reaction(R)time(p=0.032),TEG-Clot kinetics(K)time(p=0.042),Son-activated clotting time(p=0.038)and negatively with clot rate(p=0.043)in ACLF,making these correctable target variables in POC transfusion *** 223 procedures,transfusion of fresh frozen plasma and platelet concentrate was reduced by 25%(p=0.035)and 20.8%(p=0.045)by using a POC strategy in 76 *** of deranged Son-activated clotting time and TEG-reaction time was noted in 68%and 72%after 24 h of fresh frozen plasma transfusion in ACLF and 85%and 80%in cirrhosis,***:Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis,whereas use of conventional tests appear to be less suitable in patients with clinical *** Registration:NCT04332484.

关键词： coagulation Cirrhosis ACLF Validation Sonoclot Thromboelastography

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Treatment of coking wastewater using oxic-anoxic-oxic process followed by coagulation and ozonation

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Carbon Resources Conversion 2019年第2期2卷 151-156页

作者： Jianbing Wang Yuxian Ji Fengyuan Zhang Dongliang Wang Xuwen He Chunrong Wang School of Chemical and Environmental Engineering China University of Mining and Technology-BeijingBeijing 100083China

An oxic-anoxic-oxic(O-A-O)system followed by coagulation and ozonation processes was used to study the treatment of coking *** the O-A-O process,the removals of NH4+-N,total nitrogen and COD were 91.5-93.3%,91.3-92.6%and 89.1-93.8%,respectively when employing hydraulic residence times of 60 h for the biochemical *** removal of NH4+-N was obtained due to the placement of an aerobic tank in front of A-O system which can mitigate the inhibitory effect of toxic compounds in coking wastewater on nitrifying *** of methanol into the anoxic reactor greatly increased the removal of total nitrogen,indicating that denitrifiers can hardly use organic compounds in coking wastewater as carbon source for *** values of the effluent from the O-A-O system were still higher than 260 mg/L even with a prolonged time of 160 h mainly due to the high refractory properties of residual compounds in the *** subsequent coagulation and ozonation processes resulted in the COD removal of 91.5%-93.3%and reduced the relative abundance of large molecular weight(MW)organics(>1 kDa)from 55.8%to 20.93%with the ozone,PAC and PAM dosages of 100,150 and 4 mg/L *** these conditions,the COD value and concentration of polycyclic aromatic hydrocarbons in the final effluent were less than 80 and 0.05 mg/L,respectively,which meet the requirement of the Chinese emission *** results indicate that the combined technology of O-A-O process,coagulation and ozonation is a reliable way for the treatment of coking wastewater.

关键词： Coking wastewater Activated sludge process coagulation Ozonation Nitrification-denitrification

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Protein trans-splicing based dual-vector delivery of the coagulation factor Ⅷ gene

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中国科学：生命科学英文版 2010年第6期53卷 683-689页

作者： ZHU FuXiang,LIU ZeLong,CHI XiaoYan & QU HuiGe Life Science College of Ludong University,Yantai 264025,China Life Science College of Ludong University Yantai China

A dual-vector system was explored for the delivery of the coagulation factor VIII gene,using intein-mediated protein trans-splicing as a means to produce intact functional factor VIII post-translationally.A pair of eukaryotic expression vectors,expressing Ssp DnaB intein-fused heavy and light chain genes of B-domain deleted factor VIII (BDD-FVIII),was *** transient co-transfection of the two vectors into 293 and COS-7 cells,the culture supernatants contained (137±23) and (109±22) ng mL–1 spliced BDD-FVIII antigen with an activity of (1.05±0.16) and (0.79±0.23) IU mL–1 for 293 and COS-7 cells,*** spliced BDD-FVIII was also detected in supernatants from a mixture of cells transfected with inteinfused heavy and light chain *** spliced BDD-FVIII protein bands from cell lysates were visualized by Western *** data demonstrated that intein could be used to transfer the split factor VIII gene and provided valuable information on factor VIII gene delivery by dual-adeno-associated virus in hemophilia A gene therapy.

关键词： intein protein trans-splicing coagulation factor VIII dual-vector gene delivery

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Atractylenolide Ⅰ protects against lipopolysaccharide-induced disseminated intravascular coagulation by anti-inflammatory and anticoagulation effect

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Asian Pacific Journal of Tropical Medicine 2017年第6期10卷 651-657页

作者： Xiao-Mei Tang Zhi-Kai Liao You-Wei Huang Xi Lin Liang-Cai Wu Department of Obstetrics and Gynecology The First Affiliated Hospital of Jinan University Department of Pharmacology Medical College Jinan University Department of Dermatology The 6th Affiliated Hospital Sun Yat-sen University

Objective:To investigate whether atractylenolide Ⅰ(ATL-Ⅰ) has protective effect on lipopolysaccharide(LPS)-induced disseminated intravascular coagulation(DIC) in vivo and in vitro,and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ ***:New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6h at a rate of 600 μg/kg(10 mL/h).Similarly,in the treatment groups,1.0,2.0,or 5.0 mg/kg ATL-Ⅰ were *** survival rate and organ function were tested,including the level of alanine aminotransferase(ALT),blood urine nitrogen(BUN),and TNF-α were examined by *** haemostatic and fibrinolytic parameters in serum were *** 264.7 macrophage cells were administered with control,LPS,LPS + ATL-Ⅰ and ATL-Ⅰ alone,and TNF-α,phosphorylation(P)-IκBα,phosphorylation(P)-NF-κB(P65) and NF-κB(P65) were determined by Western ***:The administration of LPS resulted in 73.3%mortality rate,and the increase of serum TNF-α,BUN and ALT *** ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model,also improved the function of blood *** protein analysis indicated that ATL-Ⅰ remarkably protected liver and renal as decreasing TNF-α *** vitro,ATL-Ⅰ obviously decreased LPS-induced TNF-αproduction and the expression of P-NF-κB(P65),with the decrease of P-IκBα.Conclusions:ATL-Ⅰ has protective effect on LPS-induced DIC,which can elevate the survival rate,reduce organ damage,improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.

关键词： Atractylenolide Ⅰ Disseminated intravascular coagulation Anti-inflammatory Anticoagulation Macrophag

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Considerations for routine coagulation monitoring with rivaroxaban:A case report and review of the literature

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World Journal of Clinical Cases 2019年第3期7卷 382-388页

作者： Hai-Di Wu Hong-Yan Cao Zi-Kai Song Shuo Yang Ming-Long Tang Yang Liu Ling Qin Department of Cardiology First Hospital of Jilin University

BACKGROUND Rivaroxaban is a non-vitamin K antagonist oral anticoagulant that does not require coagulation monitoring based on current recommendations. Our goal is to explore whether routine coagulation monitoring should not be required for all patients receiving oral rivaroxaban, what relationship between routine coagulation abnormalities and bleeding, and how to deal with the above clinical situations through our case and review of the *** SUMMARY We report a 67-year-old woman with a history of atrial fibrillation who presented to the hospital with worsening dyspnea and cough. Based on electrocardiogram,venous compression ultrasonography, and computed tomography pulmonary angiography, the diagnosis of atrial fibrillation, deep venous thrombosis, and acute pulmonary embolism was confirmed. Her coagulation assays and renal function were normal on admission; she was not underweight, did not have a history of hemorrhagic disease, and her CHA2 DS2-VAS, HAS-BLED, and simplified Pulmonary Embolism Severity Index scores were 3, 0, and 0,respectively. Oral rivaroxaban(15 mg twice daily) was administered. The following day, she presented gastrointestinal and gum bleeding, combined with coagulation abnormalities. Following cessation of rivaroxaban, her bleeding stopped and tests improved over the next 2 d. Rivaroxaban was begun again 3 d after recovery. However, she again presented with gastrointestinal and gum bleeding and the abnormal tests, and the therapy was discontinued. At 30-d follow-up after discharge, she presented normal coagulation tests without *** Although current guidelines recommend that using non-vitamin K antagonist oral anticoagulants including rivaroxaban do not require coagulation monitoring,a small number of patients may develop routine coagulation test changes and bleeding during rivaroxaban therapy, especially in the elderly. Clinicians should pay attention to these patients and further obtain evidence in practice.

关键词： Rivaroxaban Routine coagulation monitoring Anticoagulation Bleeding Case report

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