Hypofibrinogenemia caused by hemocoagulase after endoscopic sinus surgery: a case report / 临床耳鼻咽喉头颈外科杂志

A 61 year-old male patient, plasma fibrinogen level was 2.98 g/L, endoscopic sinus surgery was performed under general anesthesia for polypoid of uncinate process with mycotic maxillary sinusitis. Hemocoagulase were given in pre- and post-operative for treatment. The patient was found postoperative drain blood continuously since 3 days after surgery, when the dose of hemocoagulase reach 26 KU, and fibrinogen determined in Plasma was 0.48 g/L. Coagulation returned to normal and nasal bleeding stopped after discontinuation of the hemocoagulase and supplement with fibrinogen.

Sudden Sensorineural Hearing Loss / 한양의대학술지

Sudden sensorineural hearing loss (SSNHL) is defined as a sensorineural hearing loss of at least 30 dB in 3 consecutive speech frequencies that occurred within the previous 3 days. In most cases the cause is not identified, although various infective, vascular, and miscellaneous causes have been proposed. It has a reported incidence of 5 to 20 per 100,000 patients per year. Many treatments are used, including corticosteroids, antiviral drugs, hemodilution agents, minerals, vitamins, herbal preparations, batroxobin, carbogen, and oxygen-based treatments. Intra-tympanic dexamethasone injection into the middle ear may be useful to SSNHL patients with profound hearing loss that is intractable to medical treatment or who also have diabetes mellitus. In SSNHL, early treatment with combined modalities that include steroid injection is generally recognized as the current best practice. The spontaneous recovery rates have been reported to be between 32-70%, and although various treatment protocols have been tried, only about half of patients completely recover, usually within 2 weeks. There is much to learn about pathogenesis of sudden sensorineural hearing loss, and more clinical trials are needed to establish evidence-based management.

Hypofibrinogenemia caused by long-term administration of hemocoagulase: three cases report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>A first report of 3 patients who developed hypofibrinogenemia due to long-term administration of hemocoagulase.</p><p><b>METHODS</b>The clinical data of three patients with hypofibrinogenemia due to long-term administration of hemocoagulase were analyzed, and the related literature was reviewed.</p><p><b>RESULTS</b>Case 1, a two-year old girl, had liver traumatic rupture and then treated with massive transfusion and fibrinogen infusion in addition to intravenous recombinant factor VIIa (two times) and hemocoagulase (2 U/d). The liver wound bleeding was soon stopped. However, her plasma fibrinogen level decreased to 0.12 g/L after continuous administration of hemocoagulase for 18 days. Case 2, a three-year old boy, had liver traumatic rupture and was treated with surgical repair, and then received hemocoagulase (2 U/d). On the 8th day, a large amount of blood was found to exude from abdominal cavity drainage tube and indwelling venous catheter, and his fibrinogen dropped to 0.24 g/L. Case 3 was a 45 year-old man who underwent a total mandibular resection because of malignant tumor, and he was given hemocoagulase (4 U/d). A continuous blood oozing was noted from his operation incision, and his fibrinogen level decreased to 0.25 g/L. All the three patients'plasma fibrinogen levels and coagulation tests returned to normal ranges after discontinuation of hemocoagulase administration and supplement of fibrinogen, and the bleeding stopped in cases 2 and 3.</p><p><b>CONCLUSION</b>Long-term use of hemocoagulase could induce hypofibrinogenemia and severe bleeding.</p>

A double-blind RCT of the hemostatic effects of local packing of Nasopore combined with hemocoagulase injection for postoperative management of FESS / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To compare the hemostatic effects of local packing of Nasopore combined with hemocoagulase injection and local packing of Nasopore combined with saline injection for postoperative management of functional endoscopic sinus surgery by a double-blind, randomized control clinical trial.@*METHOD@#Sixty-eight cases of chronic sinusitis needed functional endoscopic sinus surgery were randomly divided into the experimental group of 40 cases and control group of 28 cases, respectively. For the experimental group, 1 U of hemocoagulase dissolved in 0.5 ml saline was injected into Nasopore which was packed into the nasal cavity after operation. For the control group, 0.5 ml of saline was injected. The postoperative bleeding of the two groups were scored by visual analogue scale.@*RESULT@#There was statistically significant difference between the bleeding VAS scores assessed 6 hours and the ones assessed 1, 2 and 3 days after the operation in the control group (P < 0.05). There was the statistically significant difference between the bleeding VAS scores of experimental group and control group assessed 6 h after the operation (P < 0.05).@*CONCLUSION@#The hemocoagulase may improve the hemostatic effect of Nasopore 6 hours after the operation by combined injection with Nasopore as nasal cavity packing.

Effects of batroxobin on perioperative blood loss and coagulation in patients with low molecular weight heparin when undergoing the total hip replacement / 中华流行病学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Multi-center clinical study on the treatment of the low-middle frequency sudden hearing loss / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate and compare the short-term outcome of patients with low-middle frequency sudden deafness treated with alone or combination treatment.</p><p><b>METHODS</b>From August 2007 to October 2011, 205 patients with the diagnosis of low-middle frequency sudden deafness who were from 33 different clinical centers were recruited. All patients were followed up for four weeks from the initial examination. Patients were treated with steroid , Ginaton, batroxobin respectively, or Ginaton and steroid combination treatment.</p><p><b>RESULTS</b>The total effective rate was 90.73%. In Ginaton group, the total effective rate was 87.27%, 89.19% in steroid group, 87.80% in batroxobin group, and 95.83% in Ginaton and steroid group. Considering the total effective rate, there was no statistical difference between four groups (χ(2) = 7.98, P = 0.54). The clinical cure rate for steroid alone was 81.01%, Ginaton alone 76.36%, batroxobin alone 68.29%, and Ginaton and steroid combination treatment 80.56%. There were no clinically significant differences between the different treatments (P > 0.05).</p><p><b>CONCLUSIONS</b>The low-middle frequency sudden deafness tends to have a relatively favorable prognosis. The steroid played a good effect in the treatment. But different treatments either improving the microcirculation of inner ear or alleviating edema blood has undifferentiated results. Therefore the combination therapy may be more effective.</p>

Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog / 药学学报

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

Impact of hemocoagulase on coagulatory function and deep venous thrombosis after abdominal surgery / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of hemocoagulase on coagulatory function and deep venous thrombosis after abdominal surgery.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

In vitro effects of hemocoagulase atrix and its effective components on blood coagulation of patients with bleeding disorders / 中国实验血液学杂志

This study was aimed to investigate the pro coagulation effects of hemocoagulase atrix and its effective components (batroxobin and factor X activator) on plasma of normal subjects and patients with bleeding disorders and their mechanisms. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were measured. The factor (F)X activation and thrombin generation were analyzed by using chromogenic substrate method. The results showed that the plasma APTT of normal subjects was shortened by hemocoagulase atrix, batroxobin and FX activator, and the effect of FX activator was found to be concentration-dependent (r = 0.889, P < 0.05). The prolonged APTT of plasma from patients with bleeding disorders could be corrected by hemocoagulase atrix, batroxobin and FX activator, but PT showed no great changes resulted from the treatments. FX activator could promote FX activation and thrombin generation, while neither hemocoagulase atrix nor batroxobin showed such abilities. It is concluded that hemocoagulase atrix promotes coagulation process, and corrects coagulation abnormalities in patients with bleeding disorders, its main component batroxobin directly acts on fibrinogen, and FX activator promotes thrombin generation through activating FX.

A Case of Bilateral Acute Renal Cortical Necrosis Complicated by Tranexamic Acid Administration / 대한내과학회지

Acute renal cortical necrosis is an anuric form of acute renal failure. We experienced a case of renal cortical necrosis complicated by tranexamic acid administration. To our knowledge, only three cases of renal cortical necrosis have been reported worldwide. A 49-year-old man was referred with hemothorax and multiple bone fractures following a traffic accident. Tranexamic acid, and hemocoagulase were injected three times a day. After the 4th dose of hemostatics, anuria developed abruptly, the platelet count decreased to 84,000 /microL, and the serum creatinine was increased to 2.56 from 1.06 mg/dL. On the 4th Intensive Care Unit (ICU) day, computed tomography (CT) showed bilateral renal cortical necrosis with normal renal arteries and aorta. The oliguria persisted for 14 days and temporary hemodialysis was performed. The serum creatinine had decreased to 2.12 mg/dL 8 months after discharge.

A multicenter, phase III trial of hemocoagulase Agkistrodon: hemostasis, coagulation, and safety in patients undergoing abdominal surgery / 中华医学杂志(英文版)

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

A preliminary clinical study on the treatment of primary hepatic carcinoma by transcatheter arterial perfusion of batroxobin combined with TACE / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSION</b>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.</p>

Effect of plasma fibrinogen level-based defibrase therapy in patients with acute cerebral infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of individualized defibrase therapy according to the level of plasma fibrinogen (FIB) in patients with acute cerebral infarction (ACI).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Neuroprotective effect of batroxobin on experimental intracerebral hemorrhage in rats / 药学学报

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.

Effect of hemocoagulase for prevention of pulmonary hemorrhage in critical newborns on mechanical ventilation: a randomized controlled trial.

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.

Clinical analysis of non-blood transfusion treatment in patients who refused a blood transfusion for obstetrical part / 대한산부인과학회지

OBJECTIVE: The goal of this study is to analyze the clinical manifestation of obstetrical patients who refused transfusion of any blood component. Through this analysis, we could define the guideline of non-blood transfusion treatment during the obstetrical procedure. METHODS: 127 patients who visited our non-blood transfusion treatment center and had obstetrical procedures from 1 Jan. 2000 to 31 March 2006 participated in this study. They were retrospectively analyzed according to the following indexes; the reason of refusing blood transfusion, age, ratio of vaginal delivery to Cesarean section, comparison of hemoglobin level, volume of blood loss, presence of bloodless treatment, days of hospitalization, presence of blood transfusion, consequence of patient (including complications and deaths). Bloodless treatment at the hospital are medical method (recombinant human erythropoietin, Aprotinin, Hemocoagulase, Tranexamine acid, Venoferrum), Autotransfusion and Electrocauterization. RESULTS: Among 126 patients (except for 1 patient who was delivered at the other hospital), the vaginal delivery group consisted of 57, and the Cesarean operation group was 69. The most common cause of primary caesarean section was arrest disorder of cephalo-pelvic disproportion. Among 26 patients qualified for indication of transfusion, uterine atony had the highest number of patients at 16. Among the indication of transfusion, low hemoglobin level (< or =8.0 g/dL) after operation had the highest number of patients at 20. Patients qualified indication of transfusion had twice more blood loss (464.6+/-34.2 ml vs 920.5+/-214.2 ml) and two more days of hospitalization (7.6+/-0.5 day vs 9.7+/-0.6 day) compared with those of non-qualified for indication of transfusion. Nobody received direct transfusion of blood component. There were no death but acute renal failure in one patient, and DIC (disseminated intravascular coagulation) in another patient as complications. CONCLUSIONS: This study analyzed the clinical manifestations of patients who refused a blood transfusion in obstetrics. Especially, when the non-blood transfusion treatment was performed, which had been an issue in recent times, more active treatment showed less reduction of hemoglobin level than no treatment. This study also confirmed that bleeding patients can be treated by selective non-blood transfusion treatment.

Hemostatic effect of hemocoagulase agkistrodon and its mechanism / 中国实验血液学杂志

This study was aimed to investigate the hemostatic effects of hemocoagulase agkistrodon (HCA) and its mechanism. The procoagulative and hemostatic effects of HCA were evaluated by using rabbit blood coagulatin time and mouse tail bleeding time; the mechanisms of HCA hemostatic effect were analyzed by using rabbit blood clot lysis and fibrinogen lysis. The results showed that HCA shortened the rabbit blood coagulation time and the mouse tail bleeding time significantly. The effects are nearly similar to that of positive control (reptilase). HCA also induced rabbit blood clot lysis and directly hydrolysed the alpha-chain of fibrinogen. It is concluded that HCA exert its hemostatic effects by hydrolysing the alpha-chain of fibrinogen, but it is not able to induce production of XIII factor.

Recombinant batroxobin expressed highly in Pichia pastoris / 生物工程学报

Methylotrophic yeast, Pichia pastoris was used to express recombinant batroxobin, and a technology route of producing recombinant protein was finally established. We synthesized batroxobin gene artificially by means of recursive PCR. pPIC9-batroxobin was constructed and transformed into Pichia pastoris GS115 (his4). Recombinant batroxobin was expressed in yeast engineering strain and it was purified from the culture supernatant. 10 mg of recombinant batroxobin was purified from 1 liter fermentation media, it exhibited specific activity of 238 NIH units/mg and had molecular weight of 30.55 kD. The purified recombinant protein converted fibrinogen into fibrin clot in vitro, and shortened bleeding time in vivo. This study laid a foundation of development of hemostatic of recombinant snake venom thrombin-like enzyme.

Phase IIa clinical trail of hemocoagulase acutus for injection / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of hemocoagulase acutus for injection and determine its curative dose.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Relationship between the content of fibrinogen in middle ear effusion and the effect of treatment on secretory otitis media / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>