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OBJECTIVE To systematically evaluate the difference of efficacy and safety of four kinds of commonly used haemocoagulases combined with proton pump inhibitor （PPI） for nonvariceal upper gastrointestinal bleeding （NVUGIB）， and to provide evidence-based basis for clinical decision-making. METHODS Retrieved from PubMed， Web of Science， Wanfang data， VIP and CNKI databases， randomized controlled trials （RCTs） or cohort studies about Hemocoagulase agkistrodon blomhoffii， Haemocoagulase agkistrodon， hemocoagulase and Hemocoagulase bothrops atrox combined with PPI were collected during the inception to Dec. 2021. Two researchers independently screened the literature， extracted data and evaluated the quality of included studies. ADDIS 1.16.8 software was used to conduct a Bayesian network meta-analysis. RESULTS A total of 33 studies were included， involving 3 602 patients. Results of network meta-analysis showed that： in terms of hemostatic efficacy， compared with PPI monotherapy， four kinds of haemocoagulases combined with PPI could significantly improve the hemostatic efficacy of patients （P＜0.05）； there was no statistical significance in the pairwise comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： Hemocoagulase agkistrodon blomhoffii combined with PPI＞ Hemocoagulase bothrops atrox combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞hemocoagulase combined with PPI＞PPI alone. In terms of the incidence of adverse drug reactions （ADR）， compared with PPI monotherapy， there was no statistical difference in the incidence of ADR among four kinds of haemocoagulases combined with PPI （P＞0.05）. There was no statistical significance in the pairwise 88325750。E-mail：fengyufei@126.com comparison of different hemocoagulases （P＞0.05）. The optimal probabilistic ranking of network meta-analysis was as follows： hemocoagulase combined with PPI＞Hemocoagulase bothrops atrox combined with PPI＞Hemocoagulase agkistrodon blomhoffii combined with PPI＞Haemocoagulase agkistrodon combined with PPI＞PPI alone. CONCLUSIONS Compared with PPI monotherapy， four different sources of hemocoagulases combined with PPI have better efficacy and similar safety in the treatment of NVUGIB. There is no significant difference in efficacy and safety among different hemocoagulases.
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OBJECTIVE To systematically evaluate the hemostatic effect and safety of snake venom hemocoagulase drugs in abdominal surgery， so as to provide evidence-based evidence for clinic. METHODS Retrieved from Embase， Cochrane Library， PubMed， China Biomedical Literature Database， CNKI and Wanfang database， randomized controlled trials （RCTs） about 3 kinds of snake venom hemocoagulase drugs （Hemocoagulase injection， Hemocoagulase Bothrops atrox for injection， Haemocoagulase Agkistrodon for injection） in abdominal surgery were collected from the establishment of the database to Aug. 2023. Screening， quality evaluation， and data extraction were conducted on literature according to the inclusion and exclusion criteria， and Cochrane 5.1 was used for literature quality evaluation. The risk bias diagram and network diagram were drawn by Stata 15.1 software， and the Bayesian network meta-analysis was carried out by using R 3.6.2 software and Markov chain-Monte Carlo method. RESULTS A total of 11 studies were included， involving 1 401 patients， 852 in the study group， and 549 in the control group. In terms of hemostatic effect， Hemocoagulase injection was significantly superior to Haemocoagulase Agkistrodon for injection [MD＝－2.45， 95%CI （－4.39，－0.24）， P＜0.05]， and the probability of reducing intraoperative bleeding was ranked as follows： Hemocoagulase injection＞hemocoagulase B. atrox for injection＞Haemocoagulase Agkistrodon for injection； in terms of safety， there was no statistically significant difference between the three snake venom hemocoagulase drugs and placebo （P＞0.05）. CONCLUSIONS The hemostatic effect of Hemocoagulase injection in abdominal surgery is significantly better than that of Haemocoagulase Agkistrodon for injection； all three snake venom hemocoagulase drugs have good safety.
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Objective: To investigate the hemostasis effect of hemocoagulase for injection in scalp incision in craniocerebral surgery, and evaluate its effect on coagulation function and drug safety. Methods: Before undergoing craniotomy, 60 patients were randomly divid-ed into the study group and the control group. The study group was injected with hemocoagulase for injection at 1u im at the night before surgery, 1u im 1h before incision and 1u im 15min before incision. The control group was injected with 0. 9% saline at the same time with the same volume. The hemorrhagic volume, hemorrhagic volume per square decimeter, hemostatic time, blood coagulation and ad-verse events were tested and compared between the groups. Results: In the study group, the mean hemorrhagic volume was (37. 18 ± 2. 96)g, the mean hemorrhagic volume per square decimeter was (0. 23 ± 0. 16)g·cm-2and the mean hemostatic time was (125. 53 ± 36. 42)s. In the control group, the corresponding value was (60. 69 ± 2. 30) g, (0. 42 ± 0. 25) g·cm-2and (182. 72 ± 52. 29) s, re-spectively. The hemorrhagic volume, hemorrhagic volume per square decimeter and hemostatic time significantly decreased in the study group when compared with those in the control group (P<0. 05). No significant difference in blood coagulation and safety (P>0. 05). No adverse event was reported. Conclusion: Hemocoagulase for injection shows promising hemostasis effect with high safety, which can ensure craniocerebral surgery going well with shortened operation time.
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Objective:To explore the clinical efficiency and safety of hemocoagulase used in dacryocystorhinostomy. Methods:Totally 116 cases (127 eyes) of patients with chronic dacryocystitis were randomly divided into the study group and the control group. The control group 55cases(60 eyes) only received dacryocystorhinostomy,while the study group 61cases(67 eyes) received 2 units of hemocoagulase intramuscularly before dacryocystorhinostomy. The intraoperative blood loss,nasal oozing rate of nasal cavity,coagula-tion function and patency of lacrimal passages after the operation were compared,and the adverse reactions were recorded as well. Re-sults:The intraoperative blood loss and nasal oozing rate of nasal cavity on the first day after the operation of the study group were lower than those in the control group(P<0.05). For patency of lacrimal passages,there was no significant difference between the groups. After the operation,the coagulation function did not change in both groups. No obvious adverse reactions were observed in both groups. Conclusion:For the patients with chronic dacryocystitis, hemocoagulase can decrease the intraoperative blood loss and postoperative nasal oozing rate of nasal cavity for dacryocystorhinostomy.
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Objective To study the effect of the long-term administration of hemocoagulasein vitro and in vivo,whether it may cause hypofibrinogenemia and changes of cytokine interleukin-6(IL-6) expression level which related to fibrinogen synthesis.Methods Totally 50 healthy subjects pooled plasma was chose in vitro experiments,which was divided into 7 groups.After that,added various of dilutions of injection hemocoagulase and incubated at 37 ℃,detected FIB concentration every 12 h.In vivo experiments,80 rats with six-week old were randomly divided into 4 groups:negative control group,high-dose group,middle-dose group,low-dose group,After 3 weeks administration,the serum level of Ⅴfactor,Ⅷ factor,PT,activated partial thromboplastin time (APTT),FIB,IL-6 was detected.Results Hemocoagulase in vitro had a strong role to reduce fibrin,and showed a significant dose-dependent and time-dependent;Hemocoagulase prolonged low-dose use might reduce the concentration of FIB in mice,but theⅤfactor,Ⅷ factor,PT,APTT,TT were not significantly affected.Compared with the negative control group,FIB and IL-6 concentration decreased in high-dose group,middle-dose group,low-dose group and had statistically significant differences (P<0.05);The level of FIB among the groups had statistically significant differences (P<0.05).The APTT of the middle and high dose groups was slightly prolonged,which was significantly different from that of the negative control group (P<0.05).Conclusion Hemocoagulase has a strong effect to reduce the concentration of fibrin,when there is a long-term medication,fibrin concentration of the patient should be closely monitored,hemocoagulase not only directly decomposed fibrin,but also may affect the synthesis of IL-6,the specific mechanism needs further study.
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Enzymes control all metabolic processes in human system from simple digestion of food to highly complex immune response. Physiological reactions occuring in healthy individuals are disturbed when enzymes are deficient or absent. Enzymes are administered for normalizing biological function in certain pathologies. Initially, crude proteolytic enzymes were used for the treatment of gastrointestinal disorders. Recent advances have enabled enzyme therapy as a promising tool in the treatment of cardiovascular, oncological and hereditary diseases. Now, a spectrum of other diseases are also covered under enzyme therapy. But, the available information on the use of enzymes as therapeutic agents for different diseases is scanty. This review details the enzymes which have been used to treat various diseases/disorders.
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Objective To explore the clinical effect and influence of hemocoagulase on bleeding control and coagulation function in neu -rosurgery .Methods A total of 300 patients with surgical treatment in our hospital from June 2013 to June 2014 were randomly divided into control group (n=150) and observation group (n=150).The patients in control group were treated with physiological saline 10 mL topical spraying,while the patients in observation group were treated with physiological saline 10 mL plus hemocoagulase 4U topical spraying.The clinical effect and coagulation index were compared between the two groups .Results The bleeding volume of the observation group was sig-nificantly lower than that of the control group (P0.05).Conclusion Hemocoagulase treatment during the operation can reduce the volume of bleeding and transfusion of blood ,and do not affect the coagulation function in the patients .
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Objective To investigate the clinical efficacy of hemocoagulase for severe hemorrhagic cystitis (HC) following allogeneic hemotopoietic stem cell transplantation (HSCT). Methods Twenty patients undergoing allogeneic HSCT developed severe HC with an onset time of 14 to 70 days, all patients received the treatment of hemocoagulase (1 U ivgtt q12 h × 5 d). The urine speciments reserved before and after hemocoagulase were examined by naked eye and microscope to evaluate the efficacy. Results Twenty patients received the treatment of hemocoagulase. The HC was cured in 18 patients, improved in 1 patient and uncontrolled in 1 patient. For the patients with response, macroscopic hematuria disappeared at a median of 28 days (4-127 days) after the treatment. All procedures were tolerated well and no severe adverse effect was observed. Conclusion Hemocoagulase seems to be a safe and effective drug for severe HC following HSCT.
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Objective To systematically evaluate the efficacy and safety of injected hemocoagulase Agkistrodon for intraoperative bleeding.Methods We electronically searched several Chinese database till May 2014 to identify randomized controlled trials (RCTs) about injected hemocoagulase Agkistrodon for operative hemorrhage.The methodological quality of included RCTs was assessed,and the data were extracted by two reviewers independently according to the Cochrane Handbook.The homogeneous RCTs were pooled using RevMan software (Version 5.1.0).Results 2 358 articles were searched initially,and 12 RCTs involving 1 031 patients met the inclusion criteria.The results of Meta-analyses showed that:in the study groups,the average haemostatic time of the wound is shorter [OR =-40.29,95％ CI(-71.13,-9.44),P =0.01],the hemorrhagic volume of the wound [OR =-1.38,95％ CI(-1.90,-0.87),P ＜ 0.000 01],hemorrhagic volume per unit area of the wound [OR =-0.05,95％ CI(-0.06,-0.03),P ＜ 0.00001],introperative hemorrhagic volume and drainage volume on POD1 [OR =-18.52,95％ CI (-25.50,-11.53),P ＜ 0.000 01] are lower than the placebo groups.In all studies,no difference was found in the variation of hemostatic function,liver and renal function and drug-induced adverse events.Conclusions The injection of hemocoagulase Agkistrodon can significantly reduce the average haemostatic time of the wound,the hemorrhagic volume of the wound,overall introperative hemorrhagic volume and drainage volume on POD1,and does not affect the hemostatic function,liver and renal function and not increase the incidence of adverse effects or postoperative complications.
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Objective To investigate hemocoagulase hemostatic effect in lung cancer radical surgery and its effect on protease-activated receptor-1 (PAR-1 ).Methods 86 cases of pathologically confirmed lung cancer patients were randomly divided into control group and observation group,which controls were used etamsylate,observation group were used hemocoagulase,then to measure the amount of bleeding,clotting system-related factors before and after surgery,using ELISA assay to detect P-selectin,flow cytometry to measure platelet PAR-1 ,Western Blot to determine lung tissue expression of PAR-1,and the resulting data were statistically analyzed. Results The blood loss of observation group during surgery and postoperative 2d compared with the control group,had a significant difference (P<0.05 );flow cytometry results showed that,PAR-1-positive rate and P-selectin in different time periods in observation group were no statistically significant,while had a statistically significant compared with control group(P<0.05 );Western Blot detected hemocoagulase of lung tissue in patients with PAR-1 had no obvious effect,while control group had significant difference (P<0.05).Conclusion Venin hemocoagulase in lung cancer radical surgery can reduce the amount of bleeding,and be more stable for the role of the coagulation system,as well as less effect on the P-selectin and PAR-1.The results suggest that vonin hemocoagulase might not make patients with systemic hypercoagulable state in patients undergoing radical process with lung cancer,in other words it might not lead to PAR-1 highly expression to cause tumor cell metastasis.
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Objective To explore and evaluate the hemostatic effects of hemocoagulase in elderly surgery bleeding. Methods 150 cases (60~75 years old)admitted to Affiliated Hospital of Chuanbei Medical College for abdominal operation from June 2011 to June 2012 were used as subject. They were divided radomly into hemocoagulase group (50 cases),reptilase group (50 cases)and physiological saline solution group (50 cases). The hemostatic time,hemorrhagic volume,hemorrhagic volume per square unit,and body coagulation parameters in three groups were observed and compared. Results The hemorrhagic volume in hemocoagulase group was (9.2 ±2.7 )g,average hemostatic time was (124.5 ±45.7 )s,and hemorrhagic volume per square unit was (0.3 ±0.1 )g,which were similar with reptilase group,but significantly different with those in physiological saline solution group (P<0.05 ). In hemocoagulase and reptilase groups,the hemorrhagic and hemoagglution time decreased in 30 minutes and 1 day after operation, the differences were statistically significant when compared with physiological saline solution group (P <0.05 ).Conclusion Hemocoagulase has better hemostatic effect on hemorrhagic capillary in elderly surgery.
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Objective:To establish the criterion of bacterial endotoxins test for hemocoagulase atrox for injection and measure the endotoxin concentration in hemocoagulase atrox for injection by the kinetic turbidimetric technique. Methods:The limit of bacterial en-dotoxins in the product was designed according to ChP 2010. Four endotoxin concentrations were prepared to obtain the standard curve. The interfering test was done by measuring the concentration of endotoxin added into the sample solution. The endotoxin concentration in the sample solution was measured. Results:The absolute value of the correlation coefficient was 0. 988 6 (must be above or equal to 0. 980), suggesting the standard curve was valid. The recovery of the added endotoxin in the sample solution was within 50 to 200%when the concentration of the product sample was 0. 25 KU·ml-1 . The measured endotoxin concentration in the sample met the re-quirements for bacterial endotoxins. Conclusion:The bacterial endotoxins assay method for milrinone injections is established, and the kinetic turbidimetric technique is suitable for the bacterial endotoxin test of the product.
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Objective To investigate the effects of fresh isolated platelets combined with hemocoagulase on treating and preventing rehaemorrhagia after operation in the patients with cerebral hemorrhage who treated with aspirin.Methods Forty-six patients with cerebral hemorrhage who treated with aspirin were divided into combined therapy group(n =23) and simple therapy group(n =23).Eighteen patients with no aspirin treated were as control group.All patients were received the same basic treatment of small bone flap craniotomy and hemocoagulase.Moreover,patients in combined therapy group were treated with fresh isolated platelets before and after operation.The remained haematoma volume,the volume of draining,platelect aggregation rate,platelet adhesion rate,prothrombin time and activated partial thromboplastin time were measured before and after treatment respectively.Results Before treatment,the haematoma volume were(53 ± 11) ml,(51 ± 13) ml,(50 ± 15) ml in combined therapy group,basic therapy group and control group respectively,and no significant difference was found among the three groups(F =0.29,P ＞0.05).The rate of platelet aggregation and the rate of platelet adhesion in combined treatnnet group were (43.6 ± 6.2) ％ and (41.6 ± 8.5) ％,and (43.1 ± 5.0) ％,(42.7 ± 8.9) ％ in simple group,significantly lower than that in control group ((65.2 ± 6.1) ％,64.3 ±9.1) ％.F =92.93,40.93,P ＜0.05)).At 1st day after treatment,the remained haematoma volume and the volume of draining in combined therapy group were(7 ±4) ml and (301 ±21) ml,significantly lower than that in simple therapy group ((19 ± 5) ml,(413 ± 26) ml,P ＜ 0.05).While the rate of platelet aggregation (64.8 ±5.7)％ and the rate of platelet adhesion(63.3 ±6.6)％ in combined therapy group were significantly higher than that in simple therapy group ((51.6 ± 3.7) ％,(50.3 ± 7.8) ％,P ＜ 0.05).And compared to control group ((68.1 ± 5.9) ％,(67.4 ± 9.5) ％),there were no significant difference between combined therapy group and control group (P ＞ 0.05).Conclusion Fresh isolated platelets combined with hemocoagulase can improve the function of blood clotting and reduce rehaemorrhagia after operation in the patients with cerebral hemorrhage who treated with aspirin.
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Objective To observe the therapeutic effect of Famotidine combined with Hemocoagulase treating the neonatal stress ulcer complicating upper gastrointestinal hemorrhage. Methods 72 patients of stress ulcer complicating upper gastrointestinal hemorrhage were randomly divided into two groups:study group(35 cases) were treated with Famotidine plus Hemocoagulase;control group(37 cases)were cured by Famontidine only. The different therapeutic effects were compared. Results 35 cases of study group(100%)and 28 cases of control group(75.68%) were cured successfully. Compared the excellent rate of study group and control group,the former was significantly higher than the latter(P＜0.01). Conclusion Famotidine combined with Hemocoagulase treating the neonatal stress ulcer complicating upper gastrointestinal hemorrhage has notable therapeutic effect.
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OBJECTIVE:To investigate the hemostatic effect and safety of hemocoagulase in radical gastrectomy.METHODS:60 cases with gastric cancer were divided on average into 2 groups.Therapy group received hemocoagulase 2 KU during and after operation,and control group received dicynone 0.5 g and aminomethylbenzoic acid 0.2 g during and after operation.Intraoperative blood loss and amount of blood drainage at 6 h and 24 h after operation were observed.The value of D-dimer was monitored after operation.RESULTS:Intraoperative blood loss and amount of blood drainage at 6 h and 24 h after operation in therapy group were less than in control group (P
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Multiple agents can cause anaphylaxis in a perioperative setting. Identifying the agent responsible is essential for avoiding future adverse reactions as well as to attenuate the progression of anaphylaxis. Being able to distinguish an anaphylactic reaction from an anaphylactoid reaction would help clarify the therapeutic and medicolegal issues. Anaphylaxis generally occurs after reexposure to a specific antigen and requires the release of proinflammatory mediators from mast cells and basophils. An increased concentration of mast cell tryptase is a highly sensitive indicator of anaphylactic reactions during anesthesia. Botropase(R) is a procoagulant hemocoagulase purified from venom of Bothrops jararaca, a Brazilian viper and in wide use in patients with high risk of bleeding. We report a case of suspected anaphylaxis to Botropase(R) in a 67 years old female patient undergoing segmental resection of the liver with elevated concentration of serum mast cell tryptase.
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Aged , Female , Humans , Anaphylaxis , Anesthesia , Basophils , Batroxobin , Bothrops , Hemorrhage , Histamine , Liver , Mast Cells , Tryptases , VenomsABSTRACT
Objective To compare the anti-hemorrhage effect and safety of hemocoagulase and epinephrine (1∶10 000) during endoscopic mucosal resection (EMR) or polyps electrocautery. Methods Between April and November 2007,totally 60 patients received EMR or endoscopic piecemeal mucosal resection (EPMR) in our hospital because of local lesions in the esophagus,stomach or colon. The patients were randomly divided into hemocoagulase and epinephrine groups (30 cases in each) before receiving the operation. After the resection,the hemorrhage at the surgical area was measured. During the operation,the blood pressure,heart rate,and adverse effects including palpitation,dizziness,pain,and nausea were recorded. Results Immediate hemorrhage was detected in 1 case of hemocoagulase group (1/30,3%),and 6 cases of epinephrine group (6/30,20%,?2=2.588,P=0.108). No hemorrhage was observed at 24 hours in both the groups. No significantly difference was noticed in the injection volume between the two groups [(11.0?6.0) ml (5-30 ml) in hemocoagulase group vs. (11.9?7.0) ml (5-28 ml); t=-0.535,P=0.595]. In epinephrine group,the mean artery blood pressure and heart rate increased significantly after the injection [(96.9?7.9) mm Hg vs. (99.9?8.1) mm Hg,t=-3.005,P=0.005; 79.8?7.9/min vs. 84.3?8.1/min,t=-3.585,P=0.001]. Whereas,no such differences were noticed in hemocoagulase group. Five cases in epinephrine group showed transient dizziness and palpitation,and 2 patients who had esophageal lesions complained of pain at the injection site. None of the hemocoagulase group had postoperative complications. Conclusions Hemocoagulase shows same anti-hemorrhage effect as epinephrine during EMR without leading to adverse effect.
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@#ObjectiveTo evaluate the effects of two kinds of hemocoagulases, Reptilase and Baquting, on coagulation function during neurosurgical operation.Methods60 patients scheduled for craniotomy were randomly allocated into 4 groups to receive either normal saline as control (Group Ⅰ, n=15), Baquting 2 kU (Group Ⅱ, n=15), Baquting 4 kU (Group Ⅲ, n=15) or Reptilase 2 kU (Group Ⅳ, n=15) after propofol and isoflurane general anesthesia and before hypervolumic hemodilution with 6% HAES-steril 1000 ml. The blood samples were drown for testing routine blood parameters (Hb, HCT, PLT, RBC, etc.), coagulation parameters (PT, TT, APTT, INR, FIB), and sonoclotactivated clotting time (SonACT), rate of clot formation (CR) and platelet function (PF) using Sonoclot coagulation & platelet function analyzer before anesthesia, after anesthesia, at 20 min (HAES 500 ml infused), 40 min (HAES 1000 ml infused) and 120 min after the test drug was given, at the end of operation, and 24 h after operation.ResultsThere were an obvious prolongation or decrement in almost all parameters in all patients and restored to normal in the first day after operation. But the trends showed less changes in PT, TT, APTT, FIB, PF, CR in every Baquting and Reptilase groups compared with Group Ⅰ.ConclusionMedium hemodilution, coagulation and platelet dysfunctions happened during neurosurgical operation. Hemocoagulase can only partly but not significantly reverse the changes of hemostatic abilities in every group.
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The effects of hemocoagulase in injectable form (hemocoagulating enzymatic fraction of South American snake Bothrops jararaca venom provided by Ravizza) on the control of intraocular bleeding during vitreous surgery were evaluated in rabbit eyes. Intraocular infusion solution with hemocoagulase (1 NIH thrombin unit/100 ml of BSS plus) significantly reduced the bleeding time. Electroretinogram b-wave and electroretinogram c-wave showed no abnormality. Infusate with hemocoagulase (1 NIH thrombin unit/100 ml of BSS plus) is not toxic to retinal tissue and appeared to be a useful agent for the control of intraocular bleeding during vitreous surgery.