Search

Aims: The objective of this study was to evaluate the effectiveness of batroxobin in improving functional outcomes and reducing stroke recurrence among patients with acute ischemic stroke beyond the therapeutic time window for thrombolytic therapy., Methods: This multicenter, retrospective study enrolled 492 patients with acute moderate-to-severe ischemic stroke within 24 h. 238 patients were given standard (basic) therapy. On the basis of standard treatment, 254 patients received an initial intravenous infusion of batroxobin 10 U on day 1, followed by subsequent infusions of batroxobin 5 U on the 3rd and 5th days, respectively., Results: In the batroxobin group, 8.3% of patients experienced recurrence stroke, compared to 17.2% in the control group (HR, 0.433; 95% CI, 0.248 to 0.757; p = 0.003). Furthermore, intravenous batroxobin significantly improved the distribution of 90-120 day disability. Moderate-to-severe bleeding events were reported in three patients (1.2%) in the batroxobin group and one patient (0.4%) in the control group (p = 0.369)., Conclusions: Among patients with acute moderate-to-severe ischemic stroke beyond the time window for thrombolytic therapy, treatment with intravenous batroxobin had a lower risk of stroke recurrence and a better recovery of function outcome without increasing bleeding events. Prospective studies are needed to further confirm., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo., Patient and Methods: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared., Results: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar., Conclusions: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: The effect of batroxobin on hearing recovery in patients with Sudden Sensorineural Hearing Loss (SSNHL) is still controversial, and acupuncture shows auxiliary benefits for SSNHL., Objectives: To investigate the effectiveness of combining acupuncture with batroxobin therapy for patients with SSNHL., Material and Methods: One hundred and fifty-six patients with SSNHL were retrospectively enrolled in this study, and categorized into the control group (only batroxobin treatment) and observation group (batroxobin and acupuncture treatment). Pure Tone Audiograms (PTA) threshold and clinical outcomes of hearing recovery were compared. Logistic regression analysis was used to evaluate the association between hearing recovery and potential risk factors., Results: Compared to the control group, the observation group had a higher overall effective rate ( p  = 0.006) and improvement in PTA threshold ( p  = 0.007). Among SSNHL patients with high-frequency and flat-type hearing loss, observation group demonstrated superior hearing recovery post-treatment compared to the control group ( p  < 0.05). Additionally, hearing recovery in patient with SSNHL were associated with SSNHL types, disease duration, neutrophil count and acupuncture ( p  < 0.05)., Conclusions and Significance: Combining batroxobin and acupuncture treatments enhences the improvement of hearing recovery in SSNHL patients compared to only batroxobin treatments, especially high-frequency and flat-type hearing loss.

Objective: To investigate the effects of combination therapy with and without batroxobin, and the frequency of batroxobin use on the prognosis of profound sudden sensorineural hearing loss., Methods: Hearing recovery in the batroxobin group (231 patients) and non-batroxobin group (56 patients) was compared. The correlation between the number of times batroxobin was used and hearing recovery was analysed., Results: The decrease in hearing threshold and overall improvement rate in the batroxobin group with hearing loss exceeding 100 dB HL was significantly higher than that in the non-batroxobin group. There was no linear correlation between the number of times batroxobin was used and the overall improvement rate. Using batroxobin two to three times achieved a therapeutic effectiveness plateau., Conclusion: Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss exceeding 100 dB HL, and using batroxobin two to three times yields the maximum overall improvement rate.

Inflammation is pivotal in the pathogenesis and development of cerebral venous thrombosis (CVT). Herein, we aimed to assess the anti-inflammatory effects of batroxobin combined with anticoagulation in CVT. Participants were categorized into the batroxobin group (batroxobin combined with anticoagulation) and the control group (anticoagulation only). Regression analysis was employed to explore the association between the number of episodes of batroxobin administration and the fluctuation of inflammatory indicators, as well as the proportion of patients with inflammatory indicators that were reduced after batroxobin use. Twenty-three cases (age: 39.9 ± 13.8 years, female: 39.1%) in the batroxobin group and 36 cases (40.3 ± 9.6 years, 52.8%) in the control group were analyzed. Compared to the control group, batroxobin combined with anticoagulation significantly decreased fibrinogen ( P  < .001), platelet-lymphocyte ratio (PLR) ( P  = .016) and systemic immune-inflammation index (SII) ( P  = .008), and increased the proportion of the patients with lower fibrinogen ( P  < .001), neutrophil-lymphocyte ratio (NLR) ( P  = .005), PLR ( P  = .026), and SII ( P  = .006). Linear analysis showed that as the number of episodes of batroxobin administration increased, the fibrinogen ( P  < .001), the PLR ( P  = .001), and the SII ( P  = .020) significantly decreased. Logistic regression analysis showed as the number of episodes of batroxobin administration increased, the ratio of the patients with decreased NLR ( P  = .008) and PLR ( P  = .015), as well as SII ( P  = .013), significantly increased. Batroxobin could decrease NLR, PLR, and SII in CVT. The effect was related to the number of episodes of batroxobin administration. Besides reducing fibrinogen and indirect thrombolysis effects, this may be another critical benefit of batroxobin for CVT., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: Postoperative bleeding after resection of colon polyps (CPs) is an extremely common adverse event with endoscopic treatment. Hemocoagulase Bothrops Atrox (HBA) is a newly discovered hemostatic substance that contains thrombin-like and coagulation kinase-like enzymes. However, research is lacking about its use for the treatment of intestinal polyps., Objective: The study intended to examine the hemostatic efficacy and safety of a local spray treatment with HBA, derived from HBA for injection, after CP resection, to provide a new hemostatic method, support HBA's use, and provide evidence for clinical decision making., Design: The research team performed a randomized controlled study., Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei, China., Participants: Participants were 200 patients with CP who received treatment at the hospital between December 2020 and December 2022., Intervention: The research team divided participants into two groups with 100 participants each, an intervention group and a control group, using the random number expression method. For hemostasis, the intervention group received a local spray treatment that used HBA for injection, and the control group received metal-clip closure or electrocoagulation., Outcome Measures: The research team measured: (1) the hemostatic efficacy; (2) clinical outcomes-time to hemostasis, hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding; (3) at baseline and at 24h postintervention, the coagulation function-prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB); (4) at baseline and at 24h postintervention, PLT parameters-platelet count (PLT), procalcitonin (PCT), and mean platelet volume (MPV); (5) economic effects-total number of participants with hemostasis, hospital days, and total hospital costs; and (6) adverse reactions., Results: The total hemostatic efficacy for the intervention group was significantly higher than that of the control group (P = .027), and the time to hemostasis was significantly shorter (P < .001) and the hemostasis rate, rebleeding rate, and incidence of late postoperative bleeding were all significantly lower than those of the control group, at P = .009, P = .009, and P = .048, respectively. In addition, the intervention group's postoperative PT, TT, APTT, FIB, and MPV were all significantly lower than those of the control group (all P < .05), while its PLT and PCT were significantly higher than those of the control group (both P < .05). The intervention group's total number of participants with hemostasis, participants with hemostasis, hospital days, and total cost were significantly lower than those of the control group (all P < .05), while no significant difference existed between the groups in the incidence of adverse effects (P > .05)., Conclusions: HBA has an excellent hemostatic effect on intestinal polypectomy, with convenient use and high safety. In the future, popularizing the use of HBA in the treatment of intestinal polypectomy can not only effectively guarantee the postoperative safety of patients but also could reduce their economic burden and improve the quality of clinical medical services.

A percutaneous renal biopsy is an essential tool for the diagnosis of various renal diseases; however, post-biopsy bleeding is a major complication. Hemocoagulase is a detoxified and purified snake venom enzyme that is widely used to prevent post-procedural bleeding. In this study, we retrospectively analyzed the effect of hemocoagulase on post-renal biopsy bleeding. We included 221 patients who underwent percutaneous renal biopsy between April 2017 and December 2020 and analyzed post-renal biopsy hemoglobin (Hb) decline in patients who were administered a periprocedural hemocoagulase injection. After the renal biopsy, the mean Hb decrease in the entire patient cohort was 0.33 ± 0.84 g/dL. Periprocedural hemocoagulase injection lowered the Hb decline post-renal biopsy (0.50 ± 0.87 vs. 0.23 ± 0.80 g/dL, p = 0.0204). The propensity-matched cohort was also adjusted for factors influencing postprocedural bleeding; periprocedural hemocoagulase injection reduced the Hb decline post-renal biopsy (0.56 ± 0.89 vs. 0.17 ± 0.74 g/dL, p = 0.006). There were no adverse events (e.g., thrombosis and anaphylactic shock) due to hemocoagulase. Our study demonstrated the beneficial effect of hemocoagulase on post-renal biopsy Hb decline, suggesting its clinical value in preventing post-renal biopsy bleeding.

Traumatic brain injury (TBI) is the major cause of disability and mortality among young people and is associated with neurodegenerative diseases. However, the available clinical options have limited effectiveness. Here, we investigated the neuroprotective effect of Hemocoagulase Agkistrodon (HCA), a thrombin-like enzyme (TLE) isolated and purified from snake venom. Rats subjected to experimental TBI were administered a single dose of HCA or vehicle 10 min after injury. Neurological function was assessed with modified neurological severity score (mNSS). Brain edema were evaluated by measuring brain water content. Levels of hemoglobin and inflammatory cytokines were detected by Enzyme-linked immunosorbent assay (ELISA). In addition, assays including Evans blue extravasation, Western blot analysis and immunofluorescence staining were utilized to determined blood-brain barrier (BBB) integrity. Our results showed that HCA treatment ameliorated neurological deficits (p < 0.01), alleviated brain edema (p < 0.01) and hemorrhage (p < 0.01), decreased the production of the proinflammatory cytokines IL-1β (p < 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.05), and increased the anti-inflammatory cytokine IL-10 at the contusion site (p < 0.01). Moreover, HCA administration reduced BBB disruption by regulating expression of tight junction proteins, including ZO-1, occludin and claudin-5 (ps < 0.01). Together, our results demonstrate that HCA might have therapeutic efficacy in acute TBI, suggesting a potential clinical application for mitigating the neuropathological damage associated with TBI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rational: Hemocoagulase, a hemostatic, is used in patients with trauma, gastrointestinal bleeding, or pulmonary hemorrhage or those undergoing surgery. However, paradoxical bleeding after hemocoagulase administration is not considered a clinically significant adverse effect. Here, we report a case of paradoxical pulmonary hemorrhage associated with hypofibrinogenemia after administration of the hemocoagulase batroxobin in a patient with hemoptysis., Patient Concerns: An 86-year-old woman complained of hemoptysis during hospitalization with organophosphate poisoning. Hemocoagulase was administered to manage bleeding; however, bleeding signs, such as hemoptysis, massive epistaxis, and ecchymosis, recurred., Diagnoses: The patient was diagnosed with acquired hypofibrinogenemia on the basis of the reduced plasma fibrinogen level after hemocoagulase administration and lack of other causes of bleeding., Intervention: Hemocoagulase administration was discontinued, and fibrinogen-containing plasma products were administered., Outcomes: The plasma fibrinogen level normalized and bleeding signs did not recur., Lessons: It is necessary to measure plasma fibrinogen levels regularly in patients undergoing hemocoagulase administration and discontinue its administration when acquired hypofibrinogenemia is detected., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Uncontrolled bleeding associated with trauma and surgery is the leading cause of preventable death. Batroxobin, a snake venom-derived thrombin-like serine protease, has been shown to clot fibrinogen by cleaving fibrinopeptide A in a manner distinctly different from thrombin, even in the presence of heparin. The biochemical properties of batroxobin and its effect on coagulation have been well characterized in vitro . However, the efficacy of batroxobin on hemostatic clot formation in vivo is not well studied due to the lack of reliable in vivo hemostasis models. Here, we studied the efficacy of batroxobin and slounase, a batroxobin containing activated factor X, on hemostatic clot composition and bleeding using intravital microcopy laser ablation hemostasis models in micro and macro vessels and liver puncture hemostasis models in normal and heparin-induced hypocoagulant mice. We found that prophylactic treatment in wild-type mice with batroxobin, slounase and activated factor X significantly enhanced platelet-rich fibrin clot formation following vascular injury. In heparin-treated mice, batroxobin treatment resulted in detectable fibrin formation and a modest increase in hemostatic clot size, while activated factor X had no effect. In contrast, slounase treatment significantly enhanced both platelet recruitment and fibrin formation, forming a stable clot and shortening bleeding time and blood loss in wild-type and heparin-treated hypocoagulant mice. Our data demonstrate that, while batroxobin enhances fibrin formation, slounase was able to enhance hemostasis in normal mice and restore hemostasis in hypocoagulant conditions via the enhancement of fibrin formation and platelet activation, indicating that slounase is more effective in controlling hemorrhage.

Hemocoagulase is often used for hemostasis in patients with bleeding and hemorrhagic diseases, and to avoid or stanch bleeding after surgery. Herein, three patients with hepatic diseases suffering from hypofibrinogenemia were treated with hemocoagulase agkistrodon (HCA) in Peking University People's Hospital during September 2018. All the 3 patients were chronic hepatitis B patients: Patient 1 presented with hepatic carcinoma and chronic hepatitis B, and right hepatectomy was performed; patient 2 presented with chronic hepatitis B and gastrointestinal bleeding; patient 3 presented with chronic hepatitis B, acute liver failure with hematemesis, and was awaiting liver transplantation. All three patients were percutaneously injected with HCA to prevent late-onset bleeding. After HCA was discontinued, coagulation was restored to > 60 mg/dL on day 6, without injection of fibrinogen. HCA significantly reduced the need for fibrinogen in patients with hepatic diseases, and the level of fibrinogen should be carefully monitored in clinical applications.

Background: Hemocoagulase is isolated and purified from snake venoms. Hemocoagulase agents have been widely used in the prevention and treatment of surgical bleeding. A systematic review was performed to evaluate the effects of hemocoagulase on postoperative bleeding and transfusion in patients who underwent cardiac surgery., Methods: Electronic databases were searched to identify all clinical trials comparing hemocoagulase with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Two authors independently extracted perioperative data and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. Sensitivity analyses were done by examining the influence of statistical model and individual trial on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P < .05., Results: Our search yielded 12 studies including 900 patients, and 510 patients were allocated into hemocoagulase group and 390 into control group. Meta-analysis suggested that, hemocoagulase-treated patients had less bleeding volume, reduced red blood cells and fresh frozen plasma transfusion, and higher hemoglobin level than those of controlled patients postoperatively. Meta-analysis also showed that, hemocoagulase did not influence intraoperative heparin or protamine dosages and postoperative platelet counts. Meta-analysis demonstrated that, hemocoagulase-treated patients had significantly shorter postoperative prothrombin time, activated partial thromboplastin time, and thrombin time, higher fibrinogen level and similar D-dimer level when compared to control patients., Conclusion: This meta-analysis has found some evidence showing that hemocoagulase reduces postoperative bleeding, and blood transfusion requirement in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Hemocoagulase.

Batroxobin, isolated from Bothrops moojeni, is a defibrinogenating agent used as a thrombin-like serine protease against fibrinogen for improving microcirculation. Here, we investigated whether, and if so, how batroxobin restores ischemic tissue injury in terms of anti-inflammatory effects. In an in vitro flow cytometry assay for human neutrophil extracellular traps (NETs), batroxobin (DF-521; Defibrase) inhibited human NETs induced by tumor necrosis factor-α (TNF-α) in the presence of human fibrinogen. Next, the effect of batroxobin was investigated by immunohistochemistry of the anterior tibial muscle (ATM) in an ischemic hindlimb model using C57BL/6J mice intraperitoneally injected with DF-521 versus the saline control. NETs and fibrinogen deposition in the ischemic ATM decreased in DF-521-treated mice on day 2 after ischemia. Meanwhile, reverse transcription-quantitative PCR assay of the ischemic ATM unveiled continuous downregulation in the expression of the genes; Tnf-α and nitric oxide synthase2 (Nos2) with hypoxia-inducible factor-1α (Hif-1α) and vascular endothelial growth factor-a (Vegf-a) from day 3 to day 7, but the upregulation of arginase-1 (Arg-1) and placental growth factor (Plgf) with myogenin (Myog) on day 7. Daily intraperitoneal DF-521 injection for the initial 7 days into mice with ischemic hindlimbs promoted angiogenesis and arteriogenesis on day 14. Moreover, DF-521 injection accelerated myofiber maturation after day 14. Laser doppler imaging analysis revealed that blood perfusion in DF-521-injected mice significantly improved on day 14 versus the saline control. Thus, DF-521 improves microcirculation by protecting NETs with tissue defibrinogenation, thereby protecting against severe ischemic tissue injury and accelerating vascular and skeletal muscular regeneration. To our knowledge, batroxobin might be the first clinically applicable NET inhibitor against ischemic diseases., Competing Interests: The authors have read the journal's policy and have the following competing interests: Batroxobin (DF-521; Defibrase®) was supplied by Tobishi Pharmaceutical Co., Ltd. This study was financially supported by AMED under Grant Number JP19lm0203004 (HM), Tokai University School of Medicine Research Aid (HM), the Ministry of Education, Culture, Sports, Science and Technology (Academic Frontier Promotion Program and Basic Research Grant 25461091), and Tobishi Pharmaceutical Co., Ltd., under Grant Number 17A006000 (HM). The authors and Tobishi Pharmaceutical Co., Ltd., have jointly applied for a new patent entitled “Neutrophil Activation Regulator” (PCT/JP2018/001470). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation., Methods: A total of 31 CVT patients were enrolled in this real-world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times., Results: In the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61-40.7)] and segment-stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69-11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10-635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48-13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90-day follow-up (P > 0.05)., Conclusions: Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit., (© 2018 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Rectus sheath hematomas (RSHs) are uncommon. They are usually unilateral and rarely bilateral. In this paper, we report the first case of spontaneous bilateral RSHs in a uremic patient after the administration of the first dose of low-molecular weight heparin during hemodialysis. The most interesting aspect of this case is that the main symptom of RSH in our patient was urinary bladder irritation. We highlight the importance of the prompt diagnosis and management of this medical emergency.

Objective To evaluate the hemostatic effect of hemocoagulase agkistrodon on surgical wound in breast cancer surgery. Methods Totally 60 patients undergoing breast cancer surgery were enrolled in this prospective,randomized,double-blinded,and controlled study. All the patients met the inclusion and exclusion criteria and signed the informed consent. Hemocoagulase agkistrodon (2 U) was injected 20 minutes before surgery and 4 and 24 hours after surgery in the intervention group (n=30),whereas normal saline was used instead in the control group (n=30). The volume of intraoperative bleeding,wound drainage volume 1-3 days after surgery,and total drainage volume were recorded. Meanwhile,the change of blood coagulation function,treatment safety,and clinical outcomes were observed. Results The intra-operative hemorrhage volume of the intervention group [(95.0±48.3)g] was significantly lower than that of the control group [(144.8±105.4)g] (t=-2.07,P=0.044). The volume of total drainage of the intervention group [(166.7±71.2)g] was significantly lower than that of the control group [(251.4±166.3)g] (t=-2.29,P=0.029). The hemoagglutination indicators were similar in the two groups and no complication such as thrombosis occurred. The length of hospital stay of the intervention group [(15.00±3.53)d] was similar to that of the control group [(15.92±2.32)d] (t=-1.057,P=0.297). No research drug-related adverse event was occurred in our study. Conclusion Hemocoagulase agkistrodon has good hemostatic effect for patients undergoing breast cancer surgery without increasing the risk of thrombosis.

Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of diverse molecules. These biomolecules are responsible for the disturbance in fundamental physiological systems of the envenomed victim, leading to morbidity which can lead to death if left untreated. Researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements. Since the development of captopril, the first drug that was derived from bradykininpotentiating peptide of Bothrops jararaca, to the disintegrins that have potent activity against certain types of cancers, snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous development of new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents. In this review, we have focused on different snake venom proteins / peptides derived drugs that are in clinical use or in developmental stages till to date. Also, some commonly used snake venom derived diagnostic tools along with the recent updates in this exciting field are discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Aim: To evaluate the hemostatic effect of topical hemocoagulase spray in digestive endoscopy., Methods: Eighty-nine patients who developed oozing bleeding during endoscopic treatment from September 2014 to October 2014 at Center for Digestive Endoscopy, Tianjin Medical University General Hospital were randomly divided into either a study group (n = 39) or a control group (n = 50). The study group was given topical hemocoagulase spray intraoperatively, while the control group was given traditional 8% norepinephrine spray. Hemostatic efficacy was compared between the two groups. Bleeding site, wound cleanliness and perforation were recorded, and the rates of perforation and late bleeding were compared., Results: Successful hemostasis was achieved in 39 (100%) patients of the study group and in 47 (94.0%) patients of the control group, and there was no significant difference in the rate of successful hemostasis between the two groups. Compared with the control group, after topical hemocoagulase spray in the study group, the surgical field was clearer, the bleeding site was more easily identified, and the wound was cleaner. There was no significant difference in the rate of perforation between the study and control groups (16.7% vs 35.0%, P = 0.477), but the rates of late bleeding (0% vs 15.8%, P = 0.048) and overall complications (P = 0.032) were significantly lower in the study group., Conclusion: Topical hemocoagulase spray has a definite hemostatic effect for oozing bleeding in digestive endoscopy, and this method is convenient, safe, and reliable. It is expected to become a new method for endoscopic hemostasis.

Conclusions: Defibrinogenation therapy rather than corticosteroids therapy should be chosen for patients specifically with profound hearing loss and with initial high fibrinogen., Objectives: Corticosteroids therapy is the standard treatment for sudden sensorineural hearing loss (SSNHL) and prognostic factors by this therapy were reported. Defibrinogenation therapy is one of the treatment options for SSNHL. Aims of this study were to identify prognostic factors and correlative markers with hearing improvement in treating SSNHL by defibrinogenation therapy., Methods: During the early phase of the study, consecutive 61 patients were treated by defibrinogenation therapy with batroxobin (50 units), whereas corticosteroids (500 mg/day of hydrocortisone tapered by 9 days) were used for consecutive 64 patients during the late phase. Blood data that could predict a complete recovery were identified. Coagulation/fibrinolysis markers correlated with hearing improvement by defibrinogenation therapy were investigated., Results: Although there were no overall differences in hearing improvement between the two therapies, recovery rate in profound hearing loss patients was better in defibrinogenation therapy. In patients who showed complete recovery, serum fibrinogen level before treatment was significantly higher in the defibrinogenation group than the corticosteroid group. Responses of several fibrinolysis markers to defibrinogenation therapy evaluated by post-/pre-values were negatively correlated with hearing improvement.

Haemocoagulase is a snake venom protein derivative that is known to possess haemostatic activity. It is reported to minimise blood loss in orthopaedic, otorhinolaryngologic, and abdominal surgeries. The use of intravenous haemocoagulase in orthognathic surgery is unknown and not yet reported. The purpose of this trial is to study the efficacy of haemocoagulase in haemorrhage control in orthognathic surgery. Forty-six consecutive patients scheduled to undergo bi-maxillary orthognathic surgery within the time period of the study were recruited and randomized. They received either the study drug or placebo. All patients underwent operation with hypotensive anaesthesia. Intraoperative blood loss, operating time, drop in haemoglobin and haematocrit were the variables analysed in the study. Haemocoagulase caused an 11% (52 ml) reduction in blood loss in the study group (p = 0.01). There was no adverse reaction in any of the patients., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Blood transfusions may be associated with risks and the risk: benefit ratio is not always clear, even in the setting of haemorrhage., Aims: To describe the management practices and outcomes in women with profound anaemia who refused blood transfusion., Materials and Methods: Retrospective analysis over a 10-year time frame of severely anaemic women (Hb <50 g/L) with benign conditions who had requested not to receive a blood transfusion. Demographic data, clinical presentation, anaemia management practice and serious adverse events were collected from the medical record charts. Women were analysed in two groups: a gynaecologic (Gyn) and an obstetric (Ob) population., Results: A total of 19 women (12 Gyn and 7 Ob) met the inclusion criteria with a mean age of 35.8 ± 10.2 years. The lowest mean Hb concentration was 41.3 ± 9.7 g/L (Gyn Group) and 36.0 ± 8.9 g/L (Ob Group) which increased, to 67.3 ± 14.3 g/L and 73.1 ± 6.9 g/L, respectively, by the time of hospital discharge. Anaemia management initially addressed the underlying etiology and was followed by intravenous iron (all cases) plus erythropoiesis stimulating agents, haemocoagulase and/or fluids. The mean length of hospital stay was 10.5 ± 4.4 and 13.7 ± 4.1 days for the Gyn and Ob groups, respectively. No deaths or other serious complications occurred., Conclusion: These findings suggest that young and otherwise healthy women can tolerate profound anaemia (Hb <50 g/L) permitting corrective strategies to be successfully implemented without the need for blood transfusion., (© 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To investigate the interactive effects between batroxobin and low molecular weight heparin (LMWH) in reducing peri-operative blood loss and coagulation function in patients who undergone the total hip replacement surgery., Methods: 240 ASA I - III patients received 4 000 IU LMWH 12 hours preoperatively before undergoing the total hip replacement operation, were randomly divided into two groups:testing group (Group A, n = 120) and control group (Group B, n = 120) receiving 2 U batroxobin or 50 mg mannitol 10 minutes before incision respectively. Perioperative blood loss, postoperative 24 hours drainage and blood routine test, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were measured respectively. Deep vein thrombosis (DVT) were measured through color Doppler B-ultrasound 3 days after the operation., Results: The perioperative blood loss in Group A (422.64 ml) was less than that in Group B (667.67 ml) (P < 0.01) while red blood cell, hemoglobin, red blood cell volume and platelet were decreasing after operation in both groups but no significant difference was found between the two groups (P > 0.05). There were no drug-related adverse effects found in the two groups, neither the difference in hospitalization between the two groups (P > 0.05)., Conclusion: Batroxobin (2 U) could reduce the perioperative blood loss in patients with LMWH who had undergone the total hip replacement operation but did not show adverse effect on DVT.

Objective: To explore the topical hemostatic effects of batroxobin (BX) and electric cauterization (EC) on capillary hemorrhage of rabbit with a removal of carotid arterial adventitia., Methods: A total of 27 New Zealand rabbits were randomly divided into control, BX and EC groups. Each group received BX (2 kU/L), EC (power = 40 W) and saline for topical hemostasis after a removal of carotid arterial adventitia and blunt dissection. The animals were euthanized by 0, 14 and 28 d post-operation. The specimens of adventitia removal section were divided into three parts for histology (hematoxylin and eosin, MASSON & transmission electron microscope), immunohistochemistry (IHC) [monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF)] and reverse transcription-polymerase chain reaction (RT-PCR)., Results: At Day 28 post-operation, the remodeling index, stenotic rate and collagen fiber density of BX and EC groups were (0.753 ± 0.0739) and (0.618 ± 0.0989), (0.298 ± 0.030)% and (0.363 ± 0.039)%, (15.4 ± 3.5)% and (23.4 ± 5.1)% respectively. There was statistically significant difference between two groups (P < 0.05) while no difference existed between hemocoagulase and control groups. The results of electron microscopy showed that the atrial fibroblasts of EC group increased markedly versus BX group. As demonstrated by RT-PCR and IHC, the expressions of MCP-1, TGF-β1 and VEGF in BX group were lower than those in EC group (P < 0.05) while no difference versus the control group., Conclusion: As a safe and effective topical hemostatic method, BX can effectively decrease inflammation response and reduce vascular remodeling and narrowing in rabbits with a removal of carotid arterial adventitia. And its effect mimic closely natural conditions.

Aim: The present double blind study has been designed to evaluate the efficacy of local application of hemocoagulase solution as compared to a placebo in wound healing following dental extraction., Materials and Methods: A total of 20 patients who required dental extraction for orthodontic intervention were included. The hemocoagulase solution and a placebo were locally applied to the extraction sockets and the efficacy of the solution in terms of bleeding control, anti-inflammatory responses, its antiseptic properties and efficacy in wound healing were evaluated., Results: The mean time required to achieve hemostasis was found to be 1.37 minutes in side A (test) and 2.33 minutes in side B (control) indicating that side A achieved faster hemostasis when compared to side B. At the 6th hour postoperatively, bleeding was not evident on either sides, and the amount of pain in side A was found to be less compared to side B. The number of RBCs, polymorphs, chronic inflammatory cells were not different in both the groups, whereas at 3rd postoperative day epithelial cells were greater in side A (test) compared to side B (control). Biopsy reports on the 12th postoperative day indicated that the number of fibroblasts, epithelial cells, collagen count was found to be greater in side A (test) compared to side B (control)., Conclusion: The topical hemocoagulase solution may be advocated in the field of oral and maxillofacial surgery, as a hemostatic agent and promoter of wound healing. However, further studies, with large number of cases and different clinical situations should be considered to authenticate the efficacy of this hemocoagulase solution in the practice of oral and maxillofacial surgery., Clinical Significance: Wound healing plays an important role in the success of any surgical procedure, such as extractions, and the hemocoagulase system may act as a hemostatic agent and a promoter of wound healing.

Objective: To investigate the impact of hemocoagulase on coagulatory function and deep venous thrombosis after abdominal surgery., Methods: From June 2008 to January 2009, 60 cases (gastric cancer 20 cases, colonic cancer 40 cases) undergoing gastrointestinal surgery at the Union Hospital of Fujian Medical University were randomized to the hemocoagulase group and the control group(n=30 in each group). Intravenous hemocoagulase at a daily dose of 2U was used on the same day and the next day postoperatively in the hemocoagulase group. D-dimer(D-D), tissue plasminogen activator(t-PA), plasminogen activator inhibitor-1(PAI-1), PT, APTT, TT, platelet count were measured before and after operation. Doppler ultrasound examination was carried out to exclude deep venous thrombosis on the 5th to 7th days after operation., Results: Significant increased D-D, t-PA, PAI-1, prolonged PT, APTT, shortened TT and lower platelet count after surgery were noticed as compared to the baseline in both groups(P<0.05, P<0.01). PT, APTT, D-D, t-PA, and PAI-1 significantly increased, and TT significantly shortened in the hemocoagulase group as compared to the control group after surgery(P<0.05, P<0.01). Deep venous thrombosis in the left lower limbs was noticed in 7 patients(23.3%) in the hemocoagulase group and 3 cases(10.0%) in the control group, however the difference was not statistically significant(P>0.05)., Conclusions: Hypercoagulable state usually appears after abdominal surgery and use of hemocoagulase may aggravate hypercoagulability and increase the incidence of deep venous thrombosis in lower limbs after abdominal surgery. Preventative use of hemocoagulase must be administered with caution.

Background: Fibrinogen depleting agents reduce fibrinogen in blood plasma, reduce blood viscosity and hence increase blood flow. This may help remove the blood clot blocking the artery and re-establish blood flow to the affected area of the brain after an ischaemic stroke. The risk of haemorrhage may be less than with thrombolytic agents. This is an update of a Cochrane review first published in 1997 and last updated in 2003., Objectives: To assess the effect of fibrinogen depleting agents in patients with acute ischaemic stroke., Search Methods: We searched the Cochrane Stroke Group Trials Register (July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 7), the Chinese Stroke Trials Register (September 2011), MEDLINE (1950 to July 2011), EMBASE (1980 to July 2011) and Web of Science Conference Proceedings (1990 to July 2011). In addition, we searched six Chinese databases, four ongoing trials registers (July 2011) and relevant reference lists. For previous versions of the review, we handsearched journals and contacted researchers in China and Japan and relevant drug companies., Selection Criteria: Randomised trials of fibrinogen depleting agents started within 14 days of stroke onset, compared with control in patients with definite or possible ischaemic stroke., Data Collection and Analysis: Two review authors independently selected trials, assessed trial quality and extracted the data. We resolved disagreement by discussion., Main Results: We included eight trials involving 5701 patients. Six trials tested ancrod and two trials tested defibrase (patients were treated for less than three hours to less than 48 hours). Allocation concealment was adequate in seven trials. Fibrinogen depleting agents marginally reduced the proportion of patients who were dead or disabled at the end of follow-up (risk ratio (RR) 0.95, 95% confidence Interval (CI) 0.90 to 0.99, 2P = 0.02). There was no statistically significant difference in death from all causes during the scheduled treatment or follow-up period. There were fewer stroke recurrences in the treatment group than in the control group (RR 0.67, 95% CI 0.49 to 0.92, 2P = 0.01). However, symptomatic intracranial haemorrhage was about twice as common in the treatment group compared with the control group (RR 2.42, 95% CI 1.65 to 3.56, 2P < 0.00001)., Authors' Conclusions: The current evidence is promising but not yet sufficiently robust to support the routine use of fibrinogen depleting agents for the treatment of acute ischaemic stroke. Further trials are needed to determine whether there is worthwhile benefit, and if so, which categories of patients are most likely to benefit.

Microcirculatory disturbance of inner ear is probably one of the important etiological factors of sudden deafness. The purpose of this study was to evaluate the effect of retreatment on the end-stage sudden deafness. For this purpose, the patients who met with the criteria for sudden deafness and showed poor response to conventional therapy over 2 months were assigned randomly to the retreatment group. Pure tone audiometry was conducted before and after retreatment among the 103 patients (112 ears). Sodium bicarbonate and dexamethasone were injected by intravenous drip for 2 days and batroxobin 5BU for 6 days. Data were analyzed using analysis of variance and t test to determine the efficacy of retreatment. These data show that the efficacy rate in retreatment group was 46.43% and the difference between before and after retreatment was significant (P < 0.01). It was, therefore, concluded that retreatment of the end-stage sudden deafness could improve the audition of the patients and should be valuable in clinics. In this regard, the combination of sodium bicarbonate and dexamethasone proved a rational therapeutic regimen for the end-stage sudden deafness. However, further large-size multicenter studies will be required for independent validation of these findings.

Background: To compare local injection of hemostatic agents and radiofrequency (RF)-assisted hemostasis in the management of bleeding from the portal vein with varying diameters and blood flow velocities., Material and Methods: Sixteen Bama pigs were used. Laparotomy was performed to expose the liver and inner diameters and blood flow velocities of the pre-injured portal vein in the hepatic segments and subsegments were measured. Vascular injuries in the portal vein were produced (4 in each pig). The pigs were randomly divided into two groups and local injection of hemostatic agents was performed in one group and RF-assisted hemostasis in the other, both techniques monitored by contrast-enhanced ultrasonography (CEUS). Time to hemostasis was measured, and the extent of liver injury was determined 2 h after treatment., Results: In the local injection group, the rates of successful hemostasis were 100, 88.9, and 50% with portal veins with inner diameters of < 1 mm, 1-2 mm, and 2-3 mm, respectively, and the maximum time to achieve hemostasis was 24.0 ± 7.2 s. Hemostasis was not successful when the diameter was > 3 mm. In the RF-assisted group, hemostasis was successfully at all sites regardless of vessel diameter; however, the maximum time to achieve hemostasis was 156.8 ± 31.2 s. Injury to surrounding tissue was significantly greater in the RF-assisted group., Conclusion: Both methods can achieve hemostasis with small diameter portal vein injuries; however, RF-assisted hemostasis is necessary for larger vessels, though it is associated with greater damage to surrounding tissue.

Background: Adolescent idiopathic scoliosis surgery is often associated with significant blood loss and blood transfusion. In this clinical trial, the authors investigated the efficacy of reducing blood loss and allogeneic blood transfusion by using batroxobin, tranexamic acid (TXA) and the combination of the two agents., Methods: 80 adolescent patients undergoing scheduled idiopathic scoliosis surgery were randomly divided into four groups to receive 0.9% saline (group A), batroxobin (group B), TXA (group C), and both two agents in the same manner (group D). The amounts of blood loss, transfusion requirements, frozen fresh plasma (FFP) and overall drainage were assessed. The hemoglobin concentration (Hb), hematocrit and platelet counts were recorded preoperative y, postoperatively and on the first operative day. The coagulation parameters were measured meanwhile. Deep vein thrombosis (DVT) was diagnosed by ultrasound., Results: Blood loss of group B and group C decreased similarly by 35.3 and 42.8% (p = 0.212) compared with group A, while group D was reduced by 64.5, 45.1 and 37.8% compared to group A, B and C, respectively. The amount of allogeneic blood transfusion of group B and group C was comparably reduced by 57.6 and 72.4% compared to group A (p = 0.069), while group D decreased by 94.7, 87.5 and 80.9% compared to group A, B and C. Overall drainage of group B, C and D decreased by 23.0, 45.1 and 67.9% compared with group A, respectively, while group C was reduced by 28.7% compared with group B (p < 0.001). The FFP of group B, C and D was reduced by 63.4, 80.2 and 95.0% as compared with group A, while group C decreased by 45.9% as compared to group B (p = 0.025). There were no urgent coagulation disorders or DVT reported., Conclusions: In our study, batroxobin and TXA can markedly reduce the blood loss and the transfusion requirements equivalently. However, TXA performs better in minimizing FFP and the overall drainage than batroxobin. The combination seems to achieve best results and was more effective than either of the two drugs alone. No apparent adverse events were detected in these groups.

Pulmonary hemorrhage (PH) in neonates is associated with significant morbidity and mortality. Hemocoagulase is an established hemostatic agent and may be beneficial in neonates with severe PH.This systematic review was performed to investigate the clinical efficacy and safety of hemocoagulase therapy in preterm infants with Pulmonary hemorrhage (PH). The search strategy of the Cochrane Neonatal Review Group was used to determine outcomes following PH in neonates. The primary outcomes were mortality, duration of PH and length of mechanical ventilation. Other morbidities included: Respiratory Distress Syndrome, sepsis, intraventricular hemorrhage, necrotizing enterocolitis and bronchopulmonary dysplasia. The Cochrane Library, MEDLINE, EMBASE and CINAHL and bibliographies of identified trials were searched. The standard methods of the Cochrane Neonatal Review Group and van Tulder's guidelines were followed independently by the authors to assess study quality, enter data and report outcomes. Typical treatment effects were calculated using fixed confidence intervals (CI). Heterogeneity tests were performed. Two 'randomized' controlled studies related to the role of hemocoagulase in neonates were identified: One for treatment of PH and the other for prevention of PH. All preterm infants' of gestational age ≤ 32 weeks and birth weight ≤ 1500 g with PH were included in the study. A total of 48 and 72 preterm infants were enrolled and randomized into two groups in trial 1 and trial 2 respectively. Mortality risk was significantly lower in the treatment group (RR 0.52; 95%CI 0.31, 0.89, p < 0.02) when hemocoagulase was used as therapy compared to prophylactic use in neonates (RR 0.52; 95%CI 0.26, 1.07, p = 0.07). Duration of PH and mean duration of ventilation were shorter in both treatment and prophylactic groups. Use of hemocoagulase appeared to be effective in preventing PH in premature infants and reduced mortality. However, the potential risks of use of hemocoagulase including adverse effects and the effectiveness of hemocoagulase still remain uncertain due to the lack of good quality large randomized controlled studies. This needs further evaluation, before routine use can be recommended.

Purpose: Aspirin is routinely given to reduce vascular events after angioplasty. Batroxobin has been shown to effectively prevent thrombosis after angioplasty via inhibition of the fibrinogen concentration. In this randomized clinical trial, the hypothesis that batroxobin plus aspirin is more effective than aspirin alone in reducing the incidence of restenosis/reocclusion in patients with diabetes undergoing angioplasty for lower-limb ischemia., Materials and Methods: Patients with diabetes and symptomatic arterial obstructions (N = 129) were randomized to receive aspirin 100 mg/d plus batroxobin 5 IU every other day for six doses (n = 58) or aspirin alone (n = 71). The primary outcome was restenosis documented by magnetic resonance (MR) angiography or duplex imaging at 12 months. Secondary outcomes included amputation above the ankle, death, and cumulative rate of amputation or death. Kaplan-Meier analysis was used to evaluate limb salvage and survival rates., Results: After 12 months, restenosis had occurred in 43.1% and 29.7% of patients in the control and batroxobin groups, respectively (P = .0018). MR angiography and duplex imaging revealed an improved restenosis rate for infrapopliteal lesions and for lesions longer than 10 cm (P = .0016). The primary and cumulative secondary outcomes indicated significant improvements in restenosis rate, symptom relief, and amputation rates in the batroxobin group compared with the aspirin-only group. Kaplan-Meier analysis showed limb salvage and survival rates of 78.3% in the aspirin-only group and 92.2% in the batroxobin group 12 months after angioplasty (log-rank test, P = .0414)., Conclusions: Batroxobin plus aspirin reduced the rate of restenosis after arterial angioplasty, particularly in lesions located below the knee and in those longer than 10 cm, with better clinical symptom relief and improved rate of limb salvage., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Multiple sclerosis (MS) was characterized with widespread demyelination and axonal loss of central nervous system (CNS). Fibrinogen (fibrin) deposition was considered as one of the pathogenesis of MS. Therefore, we explored the effects of fibrinogen depleting agent batroxobin in experimental autoimmune encephalomyelitis (EAE) mice model. Our study showed that prevention and suppression with batroxobin significantly ameliorated clinical severity of EAE, reduced inflammatory cells infiltration, and demyelination, and suppressed the activation of astrocytes and macrophages comprising the CD11b(+) population. Batroxobin treatment leads to reduced expression of p-Akt and increased expression of MBP as compared to control. In addition, batroxobin treatment partly reversed the dendric-like formation of macrophages irritated by fibrinogen in vitro. The reduced severity of EAE mice treated with batroxobin suggests that strategy targeting fibrin as a potential therapy for EAE may be beneficial for the treatment of MS patients.

Background: We designed a small randomized clinical trial to prospectively test the hypothesis that batroxobin is more effective than aspirin alone to prevent restenosis in patients with diabetes undergoing angioplasty of infrapopliteal arteries., Methods: After a successful angioplasty, a total of 52 diabetic patients with symptomatic infrapopliteal obstructions were randomized to either the treated group (n = 26) or the control group (n = 26). Patients in the treated group received 5 IU batroxobin through an intravenous drip once every alternate day, for a total of six doses. The primary end point was restenosis and reocclusion, which was documented by magnetic resonance angiography or duplex scanning at 12-month follow-up. The clinical symptoms relief and ankle-brachial index (ABI) were compared before and after the procedure, and during follow-up. Kaplan-Meier curves were constructed to evaluate restenosis or reocclusion-free, limb salvage, and amputation-free rates., Results: Restenosis and reocclusion occurred in 22.0% and 34.5% lesions in the treated and the control group, respectively (p = 0.0307). Statistical differences were observed between the ABI before the angioplasty procedure(p < 0.05) and the ABI at the 12-month follow-up (p = 0.0094) of the two groups. Clinical symptoms improvement and tissue healing occurred in 23 and 19 patients in the batroxobin group and the control group, respectively (p = 0.0544). Twelve months after angioplasty, Kaplan-Meier analysis showed that the restenosis and reocclusion-free rate was 74.0% and 54.8%, the limb salvage rate was 96.2% and 92.3%, and the amputation-free rate was 84.6% and 84.6%, in the treated and control group, respectively., Conclusion: This pilot trial revealed that batroxobin usage was effective in preventing restenosis and reocclusion after infrapopliteal arterial angioplasty, and it might provide better clinical symptoms relief; however, it did not report preferable limb salvage or amputation-free rates., (Copyright © 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Background: Active hemorrhage arising from hepatic injury can be life-threatening and require immediate attention. At present, nonoperative management of abdominal solid organ injuries has become the usual method of care. The purpose of this study was to determine whether hemocoagulase injection alone guided by contrast-enhanced ultrasonography (CEUS) could control active bleeding in rabbit liver., Methods: The livers of 30 rabbits were punctured with an 18-gauge semiautomatic biopsy needle to create an active bleeding liver model, which was confirmed with CEUS. The animals were randomly divided into two groups: a treatment group (n=15) and a control group (n=15). In the treatment group, hemocoagulase was injected into the bleeding site under CEUS guidance. In the control group, the active bleeding site was treated with normal saline. When these treatment procedures had been performed, lactated Ringer's solution was given to both groups to maintain the mean arterial pressure at 70 mmHg for 1 hour. The intraperitoneal blood loss, hematocrit, mean heart rate, and macroscopic and microscopic examinations were analyzed at the end of the study., Results: CEUS showed hypoechoic and anechoic perfusion defects in active bleeding liver models. Macroscopic and microscopic examinations also supported the results. After the hemocoagulase injection, the former bleeding site appeared on CEUS as an area devoid of contrast. The blood loss was lower in the treatment group than in the control group (38.0+/-16.6 ml versus 107.9+/-20.8 ml; t=10.172, P<0.05). The mean hematocrit value and the heart rate were higher in the treatment group than in the control group (hematocrit: 23.9+/-3.8% versus 18.8+/-4.1%; t=3.541, P<0.05; heart rate: 250+/-18 versus 223+/-15; t=4.551, P<0.01)., Conclusion: Hemocoagulase injection alone under the guidance of CEUS is a simple and quick method to control blood loss in active liver bleeding.

Objective: To explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma (PHC) and the advantages of transcatheter arterial perfusion of batroxobin combined with transcatheter arterial chemoembolization (TACE)., Methods: 40 patients with PHC were randomized into experimental group (transcatheter arterial perfusion of batroxobin combined with TACE treatment, 20 patients) and control group (TACE alone group, 20 patients). The patients were followed up and the data were recorded, compared and analyzed., Results: (1) Compared with the control group, the FIB level in the experimental group was significantly decreased at the first month after treatment (P < 0.05). (2) The baseline of the tumor was shortened in both groups after the treatment. There was a significant difference between the two groups at different time intervals (P < 0.05). (3) After the treatment, there was a significant difference of PFS levels between the two groups (t = 2.877, P < 0.05).(4) The incidence of metastasis were 5.0% (1/20) in both groups at 6 months after treatment, and that after one year was 10.0% (2/20) in the experimental group and 25.0% (5/20) in the control group. However, the difference was not significant (chi(2) = 0.693, P > 0.05)., Conclusion: Batroxobin can rapidly and effectively decrease the FIB level. Therefore it may be used as an effective and safe adjuvant drug for the the treatment of primary hepatic carcinoma. Transcatheter arterial perfusion of batroxobin combined with TACE therapy has advantages in comparison with TACE alone. It could be taken as a new therapeutic regimen in the PHC treatment.

Objective: Multicentre clinical observation for therapeutic efficacy and clinical safety of anticoagulation and thrombolysis in deep venous thrombosis (DVT)., Methods: 127 patients with DVT in left leg were randomly divided into four groups. Group A: treated with batroxobin. Group B: use Low Molecular Weight Heparin (LMWH). Group C: batroxobin and LMWH. Group D: urokinase and LMWH. Observing the perimeter of thigh and calf periodically, monitoring coagulation function, registering the frequency and degree of the complication., Results: All the treatments in four groups can relieve the swell level of the affected legs (P < 0.05). We got the best efficacy when we use batroxobin together with LMWH (P < 0.05), especially in treating the patients with a long course of treatment. Batroxobin can obviously reduce the level of blood FBG (P < 0.05), and have no significant effect with other index of coagulation function (P > 0.05). Inject ing batroxobin into affected legs with the micro pump got a better efficacy and much safer than intravenously guttae from peripheral vein., Conclusion: Treating DVT with batroxobin got a definite efficacy, especially in cases with a long course of treatment; micro pumping can give a better effect and a high safety.

Objective: To evaluate the therapeutic effect of individualized defibrase therapy according to the level of plasma fibrinogen (FIB) in patients with acute cerebral infarction (ACI)., Methods: Sixty patients with ACI (within 72 h after onset) were randomly divided into defibrase group (n=30) and control group (n=30). The patients in defibrase group received intravenous defibrase infusion at different first doses (15, 10, and 5 U) according to plasma FIB level (>4 g/L, 2-4 g/L, and 1.3-2 g/L) before treatment. Plasma FIB was measured every 12 h after the first dose of defibrase, and when plasma FIB was over 1.3 g/L, intravenous infusion of 5 U defibrase was given to maintain plasma FIB within the range of 0.70-1.13 g/L over a period of 7 days. The plasma prothrombin time (PT), activated partial thromboplastin time (APTT) and FIB before and after the 7-day treatment were measured, and the scores of Chinese stroke scale (CSS) after 14 days of treatment and Activity of Daily Living (ADL) after 3 months were recorded., Results: After 7 days of treatment, plasma PT and APTT were significantly prolonged lengthened and plasma FIB was lowered in defibrase group. The scores of CSS improved in defibrase group after 14 days of treatment, showing significant difference from those of the control group. The clinical effective rate was 80% in defibrase group, significantly higher than that in the control group (50%). The scores of ADL after 3 months were similar between the 2 groups, but the percentage of independent living and mild dependency was significantly higher in defibrase group (93.3% vs 70.0%). No intracerebral and extracerebral hemorrhage occurred in defibrase group the during treatment, no did death occur after 3 months of treatment., Conclusion: Defibrase therapy based on plasma FIB level can rapidly and effectively lower plasma FIB, reduce neurological impairment and improve the quality of life in patients with ACI.

This study is to investigate if batroxobin has the protective effect against nerve injury caused by cerebral hemorrhage in rats and its possible mechanism. Animals were divided into sham group, model group, batroxobin 4, 8, and 16 BU x kg(-1) groups and nimodipine positive control group. On the brain stereotaxic apparatus, the rat intracerebral hemorrhage model was established by injecting collagenase with microinjector into the brain caudate nucleus which was located according to the brain stereotaxic atlas. Neuroethology of the rats was estimated. The brain tissue pathomorphology was observed with electron microscope. The water content of the brain tissue was quantitated with wet/dry weight measurement. SOD and MDA were determined according to the kit procedure, and free Ca2+ concentration in neurocyte was measured by fluorospectrophotometer. As shown in results, batroxobin could improve neuroethology scale of the rats, relieve histiocyte edema and bleeding degree. The water content of the brain tissue, MDA and free Ca2+ concentration were reduced and SOD activity was raised in batroxobin treatment groups. Therefore, it is possible that batroxobin has some protective effect against nerve injury caused by cerebral hemorrhage in rats, and its mechanism maybe relate to lessening brain edema, reducing MDA content, raising SOD activity, and inhibiting calcium overload.

We investigated whether direct injection of hemostatic agents into injury sites under the guidance of contrast-enhanced ultrasound (CEUS) can decrease blood loss from liver trauma. Twelve adult healthy dogs underwent laparotomy, and a hepatic wound (6.0 x 4.5 cm) was created in each dog. All animals were divided randomly into two groups: the treatment group and the control group. In the treatment group, hemocoagulase Atrox (Solco Basle Ltd., Birsfelden, Switzerland) and absorbable cyanoacrylate were injected directly into the liver injury sites, and 0.9% normal saline was injected into the injury sites in the control group. Resuscitation volume in the treatment group was less than that in the control group (55 +/- 12 mL vs. 105 +/- 23 mL, p < 0.001). The control group presented bleeding from liver injury sites. Times of bleeding at the injury site in the treatment groups were 6 +/- 1 s. Both groups presented an-echo and/or hypo-echo contrast regions, with contrast material pooling in the injury sites before the therapy. After the injection, the contrast material pooling disappeared in the treatment group observed by CEUS. Gross examination of liver tissue revealed that the injury site that had been treated was covered by clot and glue membrane. Histopathologic examination showed that there was hemostitic glue embolizing the microvessels and inflammatory cell infiltration among hepatocytes. Direct injection of hemocoagulase Atrox and cyanoacrylate into the liver injury sites guided by CEUS can effectively reduce blood loss from liver trauma within a short time. This experimental study may suggest a possible treatment for liver trauma hemorrhage and provide an experimental evidence for treating blunt abdominal parenchyma organs trauma under the guidance of CEUS.

Objective: To investigate the role of hemocoagulase to prevent pulmonary hemorrhage in critical newborns on mechanical ventilation., Design: Randomized controlled trial., Setting: Neonatal Intensive Care Unit of an affiliated hospital of a Medical University., Children: Seventy-two critical newborn infants on mechanical ventilation., Intervention: The involved neonates were divided randomly into two groups. Forty-one patients were treated with prophylactic hemocoagulase(dripped through the endotracheal tube), and other 31 neonates served as controls., Outcome Measures: Incidence of pulmonary hemorrhage, time of ceasing pulmonary hemorrhage if occurred, time of withdrawing of mechanical ventilation in the survivors, and mortality., Results: The incidence of pulmonary hemorrhage (12% vs 42%) and the time of ceasing pulmonary hemorrhage (1.36 +/- 0.65 vs 3.58 +/- 0.82, days), were significantly less in infants treated with prophylactic hemocoagulase as compared with the controls (P<0.05). The time to withdrawal of mechanical ventilation was less in the intervention group (3.20 +/- 0.45 vs 5.04 +/- 1.51 days) (P < 0.05). The mortality in children who received hemocoagulase was 22.0%, which was significantly less than controls (41.9 %) (P < 0.05)., Conclusion: Prophylactic use of hemocoagulase in mechanically ventilated neonates is effective against pulmonary hemorrhage.

Objective: To evaluate the efficacy and safety of hemocoagulase acutus for injection and determine its curative dose., Methods: Forty-five patients on abdominal surgeries were randomly allocated into 2 study groups and 1 control group. Thirty minutes before the operation, the patients in the study groups received intravenous hemocoagulase acutus at 1 U and 2 U, respectively, and control group had no treatment. The hemostatic time, hemorrhagic volume, and hemoagglutination were observed in all the groups., Results: The average hemorrhagic volume and hemorrhagic volume per square were significantly lower in the two study groups than in the control group (P<0.05), and the average hemorrhagic volume per square were significantly lower in study group 2 U than in the 1 U group (P<0.05). No significant differences were found in adverse effects between the 3 groups., Conclusion: Hemocoagulase acutus for injection has good hemostatic effect for controlling capillary hemorrhage at the abdominal incisions and can be safely used in the surgical patients.

Objective: To study the relationship between the fibrinogen content in middle ear effusion (MEE) and the protracted inflammation of secretory otitis media (SOM) and to explore the possible mechanism of batroxobin in treatment of SOM., Methods: The fibrinogen content of middle ear effusion from 156 patients with SOM was investigated with concretion technique at different stages. After two times punctuation of tympanum, the recurrence patients were randomly divided into two groups: batroxobin and dexamethasone group, and 0.5 ml (2 BU/ml) batroxobin or dexamethasone (2 mg/ml) was injected into middle ear cavity. The therapeutic effects were investigated., Results: The concentration of fibrinogen in the recurrence group of SOM patients was higher than that in the cured group, and even higher in the second recurrence group than in the first recurrence group (P < 0.01). There was significantly different (P < 0.001) in the therapeutic efficacy between the batroxobin group (91.6%) and the dexamethasone group (62. 5%); the difference of the fibrinogen content in MEE and air conduction of pure tone audiometry at frequencies (0.5, 1.0, 2.0 kHz) between the two groups after treatment were also significant (P < 0.01)., Conclusions: Fibrinogen may play a significant role in the occurrence and development of secretory otitis media. Batroxobin had better therapeutic effect on SOM than dexamethasone. The mechanism of batroxobin in the treatment of SOM may be that the batroxobin can relief the depressant effect of fibrinogen on surface active agents of the Eustachian tube and prevent the fibrinogen from turning into insoluble fibrin polymer by means of fibrinolysis.

Background: Fibrinogen-depleting agents are promising in the treatment of cerebral ischemic disease. They were studied by many trials, and the outcomes were different because of different regimens and different doses. In this study, we assessed the efficacy and safety of defibrase on acute cerebral infarction in China., Methods: A search using Chinese hospital knowledge database (CHKD) and MEDLINE database for randomized controlled trials was carried out. A CHKD (1994 June 2005) search was performed with the keyword "defibrase", then a second search for the keyword "acute cerebral infarction"; a MEDLINE search (1950 June 2005) was performed with the following keywords: [(cerebral ischemia), OR (acute cerebral infarction), OR (stroke)], AND [defibrase]. Meta-analysis was performed with RevMan software 4.2., Results: Included were 14 studies comparing the efficiency and safety of defibrase with other drugs in the treatment of acute cerebral infarction. Patients' records were pooled (total 646 patients; defibrase, n = 328, no defibrase n = 318). Neurological deficit score (NDS) before treatment showed weighted mean differences (WMD) = 0.95, 95% confidence interval (CI) = (-0.60, 2.50), P = 0.23; NDS after treatment showed WMD = -2.20, 95% CI = (-4.21, -0.18), P = 0.03; Barthel index at 3 months showed WMD = 4.45, 95% CI = (-0.13, 9.03), P = 0.06; the plasma fibrinogen level before treatment showed WMD = 0.02, 95% CI = (-0.16, 0.19), P = 0.86; plasma fibrinogen level after treatment showed WMD = -1.51, 95% CI = (-1.88, -1.15), P < 0.00 001., Conclusions: With the given dose and regimen of defibrase in China, defibrase may play a role of anticoagulation. It might inhibit the progression of stroke and prevent the recurrence of stroke.

A randomized placebo-controlled study has been carried out in 3 Moscow hospitals. A sample included 90 patients who survived hemispheric ischemic stroke caused by pathology in the internal carotid artery 72 h before the treatment. Forty-five patients were given standard (basic) therapy and 45 patients received adjuvant batroxobin intravenously by 1,0 ml (10BU) drops on day 1, 3 and 5 and by 0,5 ml (5BU) drops on day 7 and 9 after admitting in a hospital. Assessment of the patients' state was conducted before the treatment, on day 3, 6 and 15. The European Stroke Scale was used to measure severity of clinical symptoms. The results suggest efficacy of batroxobin the use of which provides rapid good results, especially improvement in movement disorders. The use of this drug is accompanied by defibrinating effect. The drug is well tolerated.

Objective: To evaluate the efficacy and safety of defibrase in patients with acute cerebral infarction by a large sample, multicenter, randomized, double-blind, placebo-controlled clinical trial., Methods: Patients with acute cerebral infarction within 12 hours of stroke onset were randomly assigned to receive either an initial intravenous infusion of defibrase 15 U plus normal saline 250 mL or 250 mL of normal saline only. Subsequent infusions of defibrase 5 U or placebo (normal saline) were given on the 3rd, 5th, 7th, and 9th day, respectively. Both groups received standard care of acute cerebral infarction. The primary efficacy outcome was functional status (Barthel Index) at 3 months after treatment. Safety outcome were bleeding events and mortality rate. Secondary outcome included Chinese Stroke Scale (CSS) score at 14 days and recurrence rate of stroke at 1 year., Results: A total of 1053 patients were enrolled at 46 centers from September 2001 to July 2003, and 527 patients were randomly assigned to receive defibrase and 526 to receive placebo. A similar proportion of patients in both groups completed a full course of treatment. There was a significantly greater proportion of favorable functional status (Barthel Index > or = 95) in defibrase group than in placebo group at 3 months (52.2% vs. 42.8%, P < 0.01), and the proportion of dependent functional status (Barthel Index < or = 60) was a little lower in defibrase group compared with placebo group (27.7% vs. 32.4%). These differences were more obvious among patients who were treated within 6 hours of stroke onset. Patients in defibrase group had better improvement with respect to CSS score than those in placebo group at 14 days (P < 0.05). Recurrence rate of stroke at 1 year was lower in the defibrase group compared with placebo group (6.2% vs. 10.1%, P = 0.053). Patients in defibrase group had higher risk of extracranial bleeding events (4.7% vs. 1.5%, P < 0.01) and a tendency of higher risk of symptomatic intracranial hemorrhage. The hemorrhage incidence was higher in patients with fibrinogen level < 130 mg/dL than > or = 130 mg/dL (10.6% vs. 3.8%, P < 0.05). Mortality rate at 3 months were slightly higher in defibrase group than placebo group (5.9% vs. 4.2%)., Conclusions: The defibrase is effective to improve neurological function and function of daily living for patients with acute cerebral infarction within 12 hours of symptom onset. The efficacy was even better for acute cerebral infarction within 6 hours of onset. The increased risks of intra- and extracranial hemorrhage during defibrase administration were related to the plasma fibrinogen level.

Objective: To analyze several methods of wound repair for deep partial thickness burn wounds retrospectively, so as to evaluate the significance of improvement of wound microcirculation on wound healing., Methods: (1) 2,976 burn patients admitted to our department were enrolled in the study, among them 614 undertook tangential excision, 32, eschar abrasion, 86 allo-skin coverage after debridement, 1836 tropical application of silver sulfadiazine and 408 with traditional Chinese medicine (Jing Wan Hong ointment) with gauze bandage. The results of the management with different methods were compared. (2) Rat model with deep partial thickness burn was reproduced and topical application of silver sulfadiazine was given. The rats were randomly divided into control (n = 10, with normal saline injected via caudal vein within 5 minutes postburn), and treatment (n = 10, with batroxobin injected via caudal vein within 5 minutes postburn) groups. The blood flow perfusion unit in the wound skin was measured before burn and at 0.5 to 72 postburn hours by Laser Doppler. The wound healing rate, contraction rate and wound healing time in each group were calculated on 14 and 18 postburn days (PBDs). The number of hair follicles after wound healing was observed by histological method., Results: (1) The burn wound treated by tangential excision healed within 2 to 3 post operation weeks (POWs), with the healing rate of 94.8% in patients with burn covering 50% - 70% TBSA and 93.4% in those with burn of 80% approximately 98% TBSA. The healing time of patients with allo-grafts coverage after eschar abrasion was 13.8 +/- 2.1 days without scar formation. The wound healing time was 18.0 +/- 2.3 day in 82 patients with allo-graft coverage after debridement, and it was 26.0 +/- 3.2 days with subeschar healing in 1658 patients with topical application of silver sulfadiazine. Infection in burn wound was encountered in most patients undergoing traditional Chinese medicine bandage treatment with wound healing time of 26.0 +/- 2.8 days in the lower extremities. (2) The blood flow perfusion unit of the rats in the treatment group was significantly higher than that in the control group (P < 0.01). The wound healing rate in treatment group on 14 and 18 PBD was obviously higher than that in the control group (P < 0.01). But the wound contraction rate in the two groups was similar (P > 0.05). The wound healing time in treatment group was much shorter than that in control group (P < 0.01). A few hair follicles remained in the dermis of the rats in the control group on 30 PBD, and the number was evidently smaller than that in the treatment group (P < 0.01)., Conclusion: Early tangential excision and eschar abrasion remained better methods in the management of deep partial thickness burn wounds, as they could ameliorate burn wound infection, shorten treatment period, raise wound healing rate and quality. Application of batroxobin could accelerate wound healing rate by improving wound microcirculation in deep partial thickness burn wound.

Objective: To investigate the effect of a new treatment for neonatal pulmonary hemorrhage with hemocoagulase in addition to mechanical ventilation., Methods: Forty-eight newborn infants with pulmonary hemorrhage were included and divided randomly into 2 groups. Among them, 28 patients were treated with hemocoagulase in addition to mechanical ventilation, and the other 20 neonates served as controls and were treated with mechanical ventilation only., Results: Both the length of pulmonary hemorrhage and the duration of mechanical ventilation in the survivors were significantly shortened in the infants treated with hemocoagulase in addition to mechanical ventilation as compared to controls (p < 0.05). Moreover, all infants that were unable to remain in the neonatal intensive care unit died after discharge, and when their outcome was estimated as non-survivors, the mortality in the patients with this new treatment was 39.3% (11/28), which was significantly lower than in controls (75.0%, 15/20; p < 0.05). When the discharged infants were not included in the statistics, the mortality in the hemocoagulase group was 10.7% (3/28), which was also significantly lower than in controls (40.0%, 8/20; p < 0.05)., Conclusions: The new treatment with hemocoagulase in addition to mechanical ventilation is effective in newborn infants with pulmonary hemorrhage., (Copyright (c) 2005 S. Karger AG, Basel.)

Objective: This study was designed to use urokinase (UK) in combination with batroxobin in thrombolytic therapy so as to see whether batroxobin(DF-521) would be effective for neuroprotection., Methods: The model of right middle cerebral artery occlusion (MCAO) in male SD rats was established. 120 rats were randomized into 9 groups, namely control group, sham control group, and groups that were treated with batroxobin and urokinase together or separately. Each group comprised 15 rats. Intracranial bleeding, infarct volume ratio and neurological function were observed., Results: Intracranial bleeding was found in 5 rats of the UK 5000 U/kg group, in 4 rats of the UK 5000 U/kg (2 h) + DF-521 5 BU/kg (2 h) group, and in only 1 rat of the UK 5000 U/kg (2 h) + DF-521 5 BU/kg (1 h) group. Cerebral infarct volume ratio was obviously reduced in 5 BU/kg batroxobin group. No difference was observed in neurological deficit scores., Conclusion: 5000 U/kg urokinase increased the risk of intracranial hemorrhage in rat MCAO model. Batroxobin either used separately or in combination with urokinase would not increase the risk of intracranial hemorrhage in rat MCAO model.