Efficacy of perioperative systemic tranexamic acid along with topical hemocoagulase in decreasing axillary drain output in breast cancer patients undergoing axillary lymph node dissection: A randomized, double-blind, placebo-controlled, superiority trial.

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.

Seven case reports on the prevention of hemorrhage after percutaneous computed tomography-guided core-needle biopsy of the spleen.

In this study, we reported seven patients who underwent diagnostic evaluation through core-needle biopsy (CNB) of the spleen. After biopsy, gelatin sponge particles mixed with hemocoagulase were gradually injected using a coaxial introducer needle. One patient received microwave ablation following the CNB. All patients were followed up by computed tomography to rule out bleeding or accidental injuries both immediately after the biopsy and within 24 h. Adequate specimens for pathologic examination were obtained from all patients, and the biopsy technical success rate was 100%. No serious complications were observed in our case series. There was no evidence of postbiopsy bleeding. Therefore, injection of gelatin sponge particles mixed with hemocoagulase or microwave ablation may be effective options to prevent hemorrhage after splenic core-needle biopsies.

Hypofibrinogenemia Caused by Hemocoagulase Injection: A Retrospective Study on Clinical Laboratory Findings.

Objective Hemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders. This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection.Methods We retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1, 2015 to March 31, 2018. Clinical data were collected and investigated, including clinical manifestations, hemostatic and fibrinolytic parameters, dosage of hemocoagulase, the medication time, and the cryoprecipitate blood product infusion. Differences in fibrinogen, D-dimer, and fibrin/fibrinogen degradation products (FDP) before, during, and after the application of hemocoagulase injection were analyzed statistically.Results Plasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment (F=1.80, P<0.001), with the average decrease of 2.28 g/L (0.63-3.9 g/L). After withdrawal, fibrinogen level increased significantly compared to that during the medication (F=-1.20, P<0.001), but was still lower than that before the medication (F=0.59, P=0.03). The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication (F=0.83, P=0.002; Wilcoxon-test, Z=-4.54, P<0.001). Spearman's correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemocoagulase (r=-0.17, P=0.40; r=-0.28, P=0.15; respectively) and the time of recovery from hypofibrinogenemia (r=-0.45, P=0.05; r=0.13, P=0.61; respectively).Conclusion Monitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection. Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.

Efficacy of intratympanic corticosteroid, intravenous batroxobin and combined treatment for sudden sensorineural hearing loss with type-2 diabetes.

BACKGROUND: Intratympanic corticosteroid (IC), intravenous batroxobin (IB) as the treatment for sudden sensorineural hearing loss (SSNHL) has been reported. However, the data on combination therapy (CT) was scarce. OBJECTIVE: The aim of this retrospective study was to compare the efficacy of IC, IB, and CT in the treatment of SSNHL with diabetes. MATERIAL AND METHODS: A total of 212 SSNHL patients with diabetes, who were initially treated within 14 days of onset of disease, were divided into three groups by treatment modality. The hearing recovery was evaluated by the results of pure-tone test after completion of treatment. The prognostic factors, including age, severity of initial hearing loss, duration to onset of treatment, and audiometric curve type, were further compared. RESULTS: There was a significant difference in hearing recovery by the treatment (p < .05). Recovery rates in the CT group were significantly higher in patients with early treatment than with delayed treatment (p = .021). However, duration and recovery rate was not significantly correlated in IC and IB group (p > .05). In patients recieving early treatment, the recovery rate in CT group was significantly higher than that in IC (p = .013) and IB group (p = .029). Regardless of treatment, the recovery rates were higher in patients with flat and ascending audiograms (p < .05). CONCLUSIONS AND SIGNIFICANCE: Patients receiving combined therapy, especially in the early stage of SSNHL, could achieve significantly superior recovery in the treatment of SSNHL with diabetes, compared with those using IC or IB alone.

Efficacy of combination therapy in adolescent and adult patients with total-deafness sudden sensorineural hearing loss.

BACKGROUND: Combination therapy is the first-line option for total-deafness sudden sensorineural hearing loss (SSNHL). Age may act as a crucial prognostic factor. OBJECTIVE: The aim of this study was to compare efficacy of combination therapy between adolescent and adult patients with total-deafness SSNHL. MATERIALS AND METHODS: Twenty-five adolescent patients (adolescent group) and 106 adult patients (adult group) with total-deafness SSNHL were recruited. All the recruited patients underwent initial treatment with batroxobin, methylprednisolone, and gastrodin. After 10-day treatment, hearing outcomes were determined by pure-tone average measured by audiometry. Moreover, the total effective rates in the hearing recovery and improvement of tinnitus were calculated. RESULTS: There existed no significant difference between two groups in the total effective rate of the hearing recovery (p = .110). However, a significant difference was found in the total effective rate of improvement of tinnitus between two groups (p = .016). Both adolescent and adult patients could receive the optimal hearing gains at 500 Hz (20.2 ± 13.3 and 23.1 ± 13.9dB, respectively), followed by those at 1000 Hz (18.8 ± 12.5 and 22.7 ± 14.8dB, respectively). Yet, adult patients could get better hearing gains only at 500 Hz than adolescent patients (p = .02). CONCLUSION: Compared with adult patients, adolescent patients with total-deafness SSNHL undergoing combination therapy may be less likely to have hearing recovery and the improvement of tinnitus.

The efficacy and safety of Batroxobin in combination with anticoagulation on cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is an uncommon subtype of stroke with highly variable clinical presentation. Although anticoagulation with heparin and/or warfarin remains the standard treatment for CVST, treatment failure is still common. This study aims to evaluate the safety and efficacy of Batroxobin in combination with anticoagulation on CVST control. In this retrospective study, a total of 61 CVST patients were enrolled and divided into Batroxobin (n = 23) and control (n = 38) groups. In addition to the same standard anticoagulation in control, patients in the treatment group received Batroxobin 5 BU intravenous infusion (10 BU for the first time) every other day, for a total of three infusions. A higher recanalization rate was found in Batroxobin group (adjusted OR [95% CI] of 2.5 [1.1-5.0], p = 0.028) compared to the control group, especially in patients with high levels of fibrinogen (adjusted OR [95% CI] of 4.7 [1.4-16.7], p = 0.015). Statistically significant differences between the two groups were seen regarding the levels of thrombin time, fibrinogen and D-dimer at each cut-off time point (all p < 0.01). Compared with baseline, NIHSS scores at discharge showed significant improvement in the Batroxobin group [0(0, 4.25)-5(2, 11), p = 0.036]. No significant difference in mRS scores was found between the two groups at discharge or at 6-month outpatient follow-up (all p > 0.05). Additionally, Batroxobin did not increase the risk of intracranial hemorrhage. We conclude that Batroxobin is a potentially safe and effective adjunct therapeutic agent promoting CVST recanalization especially in patients with high level of fibrinogen.

Coagulant Effect and Tolerability of Yeast-Produced Recombinant Batroxobin in Healthy Adult Subjects.

BACKGROUND AND OBJECTIVE: Batroxobin, a snake venom thrombin-like enzyme, converts fibrinogen into fibrin by cleaving fibrinopeptide A. It is used for hemostasis; however, the supply of native batroxobin is limited. Therefore, we developed a recombinant batroxobin (r-batroxobin) from Pichia pastoris and evaluated its pharmacodynamics and safety in humans. METHODS: A randomized, double-blind, placebo-controlled, single ascending-dose study was performed. Eight healthy subjects were enrolled in each r-batroxobin dose group (2.5, 5.0, or 10.0 BU/2.0 mL administered intravenously), and randomized to receive r-batroxobin (n = 6) or matching placebo (n = 2). Safety was evaluated during the study, and pharmacodynamics was assessed using prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen level. RESULTS: All subjects in each cohort completed the study. No significant changes in PT or aPTT occurred after intravenous r-batroxobin administration. Compared with the placebo group, the fibrinogen level in all r-batroxobin dose groups decreased significantly to 8.68-33.57% from the baseline within 12 h (p ≤ 0.05). The TT in the 5.0 and 10.0 BU/2.0 mL groups significantly increased to 7.53-18.48% from baseline within 12 h compared with that of the placebo group (p ≤ 0.05), whereas that of the 2.5 BU/2.0 mL group exhibited non-significant changes compared with the placebo group. No serious adverse events occurred. CONCLUSIONS: A single intravenous injection of r-batroxobin within a dose range of 2.5-10.0 BU/2.0 mL was well tolerated and resulted in a significant decrease in fibrinogen and prolongation of TT. REGISTRATION: This study is registered at the Clinical Research Information Service (CRIS, http://cris.nih.go.kr ), number KCT0002518.

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery.

STUDY DESIGN: A prospective randomized double blind placebo controlled trail. OBJECTIVE: To evaluate and compare the efficacy and safety of batroxobin (botropase), tranexamic acid (TXA), and their combination in reduction of perioperative blood loss in lumbar spine single level fusion surgeries. SUMMARY OF BACKGROUND DATA: Spinal surgeries are associated with significant blood loss leading to perioperative anemia and increased need for allogenic transfusion. TXA competitively inhibits plasmin and batroxobin converts fibrinogen to fibrin and theoretically their combination is synergistic. Though TXA is widely studied in controlling blood loss, there is little information on use of batroxobin and their combination. Thus, we aimed to study effect and safety of individual drugs and their combination in controlling blood loss in spinal surgery. METHODS: Hundred patients were randomized into four groups. Group B received batroxobin, group T received TXA, group BT received batroxobin and TXA and group P received placebo. Outcomes assessed are intraoperative and postoperative blood loss, hematocrit, allogenic blood transfusion, and deep vein thrombosis (DVT), postoperatively. RESULT: Mean intraoperative blood loss in Group B, T, BT, and P were 268.32 ±â€Š62.92 mL, 340.72 ±â€Š182.75 mL, 256.96 ±â€Š82.64 mL, and 448.44 ±â€Š205.86 mL, respectively. Postoperative surgical site drain collection in Group B, T, BT, and P were 218.00 ±â€Š100.54 mL, 260.40 ±â€Š100.85 mL, 191.00 ±â€Š87.84 mL, and 320.00 ±â€Š125.83 mL, respectively. Intraoperative blood loss of Group P was statistically higher than Groups B and BT (P < 0.001). Mean postoperative surgical site drain collection was statistically significant (P < 0.001). No statistically significant differences in fluid administration (P = 0.751), blood transfusion (P = 1.000), preoperative and postoperative hemoglobin (P = 0.090, P = 0.134, respectively), and deep vein thrombosis (P = 1.000). CONCLUSION: Batroxobin and combination of batroxobin with tranexamic acid significantly reduced perioperative blood loss when compared with placebo. LEVEL OF EVIDENCE: 2.

Hemocoagulase Combined with Microbubble-Enhanced Ultrasound Cavitation for Augmented Ablation of Microvasculature in Rabbit VX2 Liver Tumors.

We investigated a new method for combining microbubble-enhanced ultrasound cavitation (MEUC) with hemocoagulase (HC) atrox. Our goal was to induce embolic effects in the vasculature and combine these with an anti-angiogenic treatment strategy. Fourteen days after being implanted with a single slice of the liver VX2 tumor, rabbits were randomly divided into five groups: (i) a control group injected intra-venously with saline using a micropump; (ii) a group given only an injection of HC; (iii) a group treated only with ultrasound cavitation; (iv) a group treated with MEUC; (v) a group treated with MEUC + HC. Contrast-enhanced ultrasound was performed before treatment and 1 h and 7 d post-treatment to measure tumor size, enhancement and necrosis range. QontraXt software was used to determine the time-intensity curve of tumor blood perfusion and microvascular changes. At 1 h and 7 d after treatment with MEUC + HC, the parameters of the time-intensity curve, which included peak value, regional blood volume, regional blood flow and area under the curve value and which were measured using contrast-enhanced ultrasound, were significantly lower than those of the other treatment groups. The MEUC + HC treatment group exhibited significant growth inhibition relative to the ultrasound cavitation only, HC and MEUC treatment groups. No damage was observed in the surrounding normal tissues. These results support the feasibility of reducing the blood perfusion of rabbit VX2 liver tumors using a new method that combines MEUC and HC.

Hypofibrinogenemia Caused by Hemocoagulase After Colon Polyps Excision.

BACKGROUND In patients with large colon polyps, late-onset bleeding may be more likely to occur because of the larger cutting surface. In these patients, hemostatic agents may be applied to prevent the late-onset bleeding. A total of 7 patients developed hypofibrinogenemia caused by hemocoagulase following excision of colon polyps in our center from November to December 2015. CASE REPORT Seven patients underwent excision of colon polyps in our center from November to December 2015. The cutting face was large in these patients after surgery; therefore, hemocoagulase was used to prevent potential late-onset bleeding. Evaluation of clotting function showed that the fibrinogen level was normal before surgery in all 7 patients. Hemocoagulase was intravenously administered twice daily beginning from postoperative day 1. Hypofibrinogenemia of varying severity occurred 2-4 d later. Three patients also had lower-gastrointestinal bleeding. After drug withdrawal and infusion of fibrinogen, blood fibrinogen level gradually returned to normal. In contrast, among 13 patients who had not received hemocoagulase treatment for preventing hemorrhage following excision of colon polyps, detection of blood fibrinogen before surgery and 2-4 d after showed normal results. CONCLUSIONS Routine use of Hemocoagulase For Injection for the prevention of late-onset bleeding is not recommended for patients who have undergone excision of colon polyps. Hemocoagulase following excision of colon polyps can cause hypofibrinogenemia and even lower-gastrointestinal bleeding.

Bilateral rectal sheath hematomas after low-molecular weight heparin treatment in uremia.

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.

The impact of hemocoagulase for improvement of coagulation and reduction of bleeding in fracture-related hip hemiarthroplasty geriatric patients: A prospective, single-blinded, randomized, controlled study.

BACKGROUND: Uncontrolled bleeding is associated with poor outcomes and mortality in geriatric patients undergoing hemiarthroplasty. Hemocoagulase agkistrodon is a hemocoagulative, anti-hemorrhagic enzyme complex from Deinagkistrodon acutus snake venom. This study aimed to investigate the efficacy of hemocoagulase agkistrodon on coagulation and bleeding outcomes in fracture-related hemiarthroplasty. PATIENTS AND METHODS: This was a prospective, single-blinded, randomized controlled trial carried out between October 2013 and September 2014 in 96 geriatric patients undergoing hemiarthroplasty for unilateral femoral neck fracture. Patients were administrated hemocoagulase agkistrodon (n=48) or normal saline (n=48). Intraoperative blood loss, transfusion volume and rate, and drainage were assessed. Hemoglobin (Hb) and coagulation parameters (prothrombin time [PT], thrombin time [TT], plasma fibrinogen [FIB], and activated partial thromboplastin time [aPTT]) were recorded preoperatively and 30min and 1, 3, and 5days after surgery. Complications were followed up for 4 weeks. RESULTS: Compared to controls, hemocoagulase patients exhibited lower intraoperative blood loss (P<0.01) and postoperative blood loss, total drainage, mean transfusion volume, and transfusion rates (all P<0.05), with lower aPTT at 30min (P<0.05). No significant differences in postoperative FIB were observed. Controls exhibited significantly higher PP and TT on day 1, and Hb on days 1, 3, and 5 (P<0.05). No serious complications were reported. CONCLUSIONS: Hemocoagulase reduced blood loss and transfusion in fracture-related hip hemiarthroplasty without increasing short-term adverse event rates. In geriatric populations, hemocoagulase could be used for limiting bleeding and related complications. TRIAL REGISTRATION: This trial is registered in the Chinese Clinical Trial Register (no. ChiCTR-TRC-14004379).

Evaluating renal biopsy-associated hemorrhage complications by the equation and providing an early intervention: a single-center experience.

BACKGROUND: The aim was to evaluate the risk for major hemorrhage complications (MHC) prior to percutaneous renal biopsy and apply a specific procedure in high-risk patients to decrease their incidence. Hemorrhage complications that required blood transfusion or other interventions were diagnosed as MHC. METHODS: One retrospective (Group A, n = 1314) and two prospective cohorts (Group B, n = 249 and Group C, n = 422) were involved in the study. Group A was used to establish a risk equation for MHC, Group B to test its performance, and Group C to evaluate the efficacy of the proposed procedure to reduce MHC incidence. Group C was classified, based on the equation, into high-risk (C1) and low-risk (C2) patients, who received different interventions. The intervention in Group C1 consisted of use of 18-gauge needles, a 12-h rest period post-operation, and reptilase injection; in Group C2, 16-gauge needles were used, with a 6-h rest, and no reptilase injection. Group B was also divided into B1 (high-risk) and B2 (low-risk) using the same cut-off, for further comparison. RESULTS: (1) In Group A, 4.8% of patients experienced MHC and the equation: Logit (PMHC) = 0.022 × mean arterial pressure (mmHg) + 0.216 × bleeding time (min) - 0.011 × eGFR [ml/(min 1.73 m(2))] - 0.894 × kidney length (cm) - 2.100 × renal cortical thickness (cm) + 6.225 (cutoff = -1.664) was established. (2) The area under the receiver operating characteristic curve was 0.848 (95 % CI 0.797-0.890) for Group B. (3) MHC occurred in 4.8 and 2.8% of patients in Group B and C, respectively; Group B1 suffered significantly more frequent gross hematuria, hematoma and MHC than Group C1; however, no significant difference except for large hematoma was found between Groups B2 and C2 for all complications. CONCLUSIONS: The equation is reliable to predict the risk for MHC; the interventions proposed can decrease the incidence of MHC in high-risk patients.

The beneficial effect of Batroxobin on blood loss reduction in spinal fusion surgery: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVE: Our objective was to evaluate the efficacy and safety of Batroxobin on blood loss during spinal operations. METHODS: After obtaining approval from the ethics committee at the hospital along with informed written consent, we performed a double-blind, randomized, placebo-controlled study with 100 patients who were randomized equally into 2 groups (Batroxobin and placebo). Patients received either 2 ku IV 15 min before surgery and followed 1 ku IM of Batroxobin following surgery, or an equivalent volume of placebo (normal saline). Cost of Batroxobin treatment is amounted to 84.75 euros. The primary outcomes were intraoperative, 24 h postoperative, and total perioperative blood loss. Secondary outcomes were hemoglobin (Hb), red blood cell count (RBC), the volume of blood/fluid transfusion intraoperatively, and 24 h postoperatively. Safety evaluation parameters were the incidence of venous thrombosis in the lower extremities, active partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen. The data were analyzed using the Statistical Package for the Social Science Version 12.0. The results were presented as mean ± SEM. The Mann-Whitney test and Independent Student t test, when appropriate, were used to compare the 2 groups, and differences were considered significant if the P value was <0.05. RESULTS: 88 patients were included in the analysis while 12 patients were withdrawn from the study due to extended surgical duration, change of surgical procedure, or after the patients' request. The total perioperative blood loss was approximately 31% lower in patients given Batroxobin versus placebo (700.5 ± 45.81 vs 485.7 ± 30.01 mL, P = 0.001). The Batroxobin group had significantly less intraoperative blood loss (326.1 ± 24.16) compared to the placebo group (556.0 ± 43.58), but there was no difference in the amount of blood/fluid transfused, postoperatively Hb, or RBC between the two groups. After the operation, coagulation parameters were not significantly different between the 2 groups at the days 1 or 3 postoperatively. No adverse events related to the use of Batroxobin were recorded. There were no cases of superficial wound infection. None of the subjects died during the study. CONCLUSIONS: In this study, prophylactic use of Batroxobin provided an effective and cheap method for reducing blood loss without coagulopathy during or after operations. The use of Batroxobin for patients undergoing one-level PLIF surgery safely and effectively reduced the total amount of perioperative blood loss.

[A double-blind RCT of the hemostatic effects of local packing of Nasopore combined with hemocoagulase injection for postoperative management of FESS].

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 with continuous transcranial Doppler monitoring in patients with acute cerebral stroke: a randomized controlled trial.

Our objective was to determine whether continuous transcranial Doppler (TCD) monitoring could safely enhance the efficacy of batroxobin, a thrombin-like enzyme extracted from Bothrops atrox moojeni venom, in the treatment for acute cerebral stroke beyond the thrombolytic time window. Ninety patients suffering an acute cerebral stroke were recruited into the study within 12 hours after the onset of symptoms. Patients were randomized to receive batroxobin with (target group) or without 1 hour of continuous TCD monitoring (control group). Clinical evaluation of stroke was based on the National Institutes of Health Stroke Scale (NIHSS) score, Barthel index (BI), Thrombolysis in Brain Ischemia score (TIBI), the incidence of advancing stroke, and the recurrence of cerebral infarction. The patients receiving continuous TCD monitoring showed significant improvement in NIHSS score at 57 days post treatment compared with the control. Similarly, patients receiving continuous TCD monitoring also showed significant improvement in BI at 3 months compared with the controls. Consistently, both the incidence of advancing stroke after 1 week and the incidence of stroke recurrence after 3 months were significantly lower in TCD monitored group than control group. Moreover, the safety of the employment of TCD monitoring in the treatment of these patients was confirmed as there was no significant difference of the incidence of intracranial hemorrhage at 1 week after the treatment between the target and control groups. Taken together, our study showed that batroxobin, in combination with continuous TCD monitoring at the middle cerebral artery, reduced the incidence of advancing stroke and stroke recurrence after treatment without adverse effects in terms of poststroke intracranial hemorrhage.

[Hypofibrinogenemia caused by long-term administration of hemocoagulase: three cases report and literature review].

OBJECTIVE: A first report of 3 patients who developed hypofibrinogenemia due to long-term administration of hemocoagulase. METHODS: The clinical data of three patients with hypofibrinogenemia due to long-term administration of hemocoagulase were analyzed, and the related literature was reviewed. RESULTS: 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. CONCLUSION: Long-term use of hemocoagulase could induce hypofibrinogenemia and severe bleeding.

Contrast-enhanced sonographically guided percutaneous 915-MHz microwave ablation therapy compared to local hemostatic drug injection in a renal artery injury model.

OBJECTIVES: The purpose of this study was to show the contrast-enhanced sonographic features of various levels of renal artery rupture and to validate the therapeutic effects of percutaneous 915-MHz microwave ablation compared to hemostatic drug injection (batroxobin) using an in vivo canine renal artery injury model. METHODS: Three renal artery hemorrhage models (A, diameter <1 mm, subcapsular artery; B, diameter 1-2 mm, interlobar artery; and C, diameter 2-3 mm, segmental artery) were created in 24 canines for this study. Contrast-enhanced sonography was used to show the bleeding features and guide hemostatic therapies using 915-MHz microwave ablation and local batroxobin injection. Success rates were assessed according to amounts of bleeding, times required for hemostatic action, and volumes of fluid infusion required using pathologic examination as a reference standard. RESULTS: Contrast-enhanced sonography clearly showed renal artery ruptures with active bleeding at various levels and degrees and was very useful to make diagnoses and guide therapies. The success rate in the microwave treatment group was higher than that in the drug injection group (except group A; P< .05). The time required for hemostasis and the volume of fluid infusion required in the microwave group were notably less than those in the drug injection group (P < .05). CONCLUSIONS: Contrast-enhanced sonography is a useful imaging method for assessing renal vessel injury and guide interventional therapies. Contrast-enhanced sonographically guided percutaneous 915-MHz microwave ablation is a preferred hemostatic technique for treatment of renal artery injury, with greater effectiveness and less tissue damage compared to local drug injection.

The effective control of a bleeding injury using a medical adhesive containing batroxobin.

Many types of hemostatic agents have been studied for the effective control of bleeding. In this study, a powdery medical adhesive composed of aldehyded dextran and ε-poly (L-lysine) was used with the recombinant batroxobin. Batroxobin is a venomous component from the snake Bothrops atrox moojeni and catalyzes fibrinogen conversion to form soluble fibrin clots. This research aims to examine the performance of the batroxobin-containing adhesive for hemostasis, and evaluate its potential as a novel hemostatic adhesive. The fibrinogen conversion ability of batroxobin was evaluated by a fibrinogen clotting assay and a whole blood clotting assay. Both experiments demonstrated the effectiveness of the batroxobin-containing adhesive for blood clot formation. Animal experiments were also conducted. After a pricking wound was made in an ICR (imprinting control region) mouse liver, the adhesive and various concentrations of batroxobin were applied. The total amount of blood loss was reduced with increasing concentrations of batroxobin. For excessive bleeding conditions, the femoral artery wound model of SD (Sprague-Dawley) rats was adopted. With higher concentrations of batroxobin, hemostasis was more rapidly achieved. Histological analysis of the liver model also supports the hemostatic effects through fibrin clot formation. In conclusion, batroxobin and medical adhesive effectively facilitate blood coagulation, and could be developed for clinical use.