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.

Analysis of Hemostatic Effect and Safety of Local Spray Treatment With Hemocoagulase Bothrops Atrox for Injection After Resection of Colon Polyps.

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.

Effectiveness and safeties of hemocoagulase and tranexamic acid to reduce perioperative blood loss in intertrochanteric fracture PFNA fixation.

This study evaluated the efficacy of hemocoagulase and tranexamic acid (TXA) in minimizing perioperative blood loss in perioperative period of proximal femoral nail antirotation (PFNA) repair. 99 patients having intertrochanteric fracture PFNA fixation were randomly assigned to the hemocoagulase, TXA, and control groups (n=33 per group). In the hemocoagulase group, 1 KU of hemocoagulase was injected preoperatively and postoperatively local sprayed, respectively; in the TXA group, 0.5g TXA was injected preoperatively and postoperatively local sprayed, respectively; and in the control group, 100 mL of physiological saline was injected before surgery and was used by postoperative local spraying, respectively. The hemocoagulase and TXA groups exhibited significant differences in preoperative hemoglobin (HB) and hematocrit (HCT) levels on postoperative days 1 and 3, intraoperative bleeding, 24-hour postoperative drainage, total perioperative bleeding, transfusion rate, and postoperative hospitalization duration compared to the control group. Furthermore, the hemocoagulase and TXA groups showed significant differences in postoperative day 3 HB and HCT levels and postoperative hospitalization duration compared to each other. In conclusions, the combined use of systemic preoperative and local postoperative hemocoagulase and TXA spraying is found to significantly decrease perioperative blood loss in intertrochanteric fracture patients undergoing PFNA. Hemocoagulase is observed to have a superior effect compared to TXA.

Serum Levels of VWF, t-PA, TNF-α, and ICAM-1 in Patients Receiving Hemocoagulase Combined with Platelet-Rich Plasma during Total Hip Replacement.

Objectives: This study aimed to investigate the effect of hemocoagulase combined with platelet-rich plasma (PRP) in total hip replacement (THR) on reducing bleeding and improving knee joint function in the patients with osteoarthritis. Methods: From February 2018 to February 2020, 80 osteoarthritis patients undergoing THR were included in the study, of which 40 cases were treated with PRP and hemocoagulase (test group) in the joint capsule in THR and the other 40 cases received saline and thrombin in the joint capsule after THR (control group). Postoperative drainage and corresponding functional exercise were performed for the two groups 12 hours after operation. The outcome measures including operation time, soft-tissue release, blood routine, drainage volume, perioperative blood loss, postoperative incision inflammation, deep vein thrombosis (DVT), and range of motion (ROM) of the joint were recorded. Results: The hemoglobin and hematocrit values of the test group on the second postoperative day were significantly higher than those of the control group (P < 0.05). The postoperative drainage volume and perioperative blood loss were significantly lower than those of the control group (P < 0.05). The test group was better than the control group in the ROM of the joint at 7 and 15 days after the operation (P < 0.05). A lower value of prothrombin time and activated partial thromboplastin time was revealed in the test group compared with the control group (P < 0.05). No significant difference in the operation time, intraoperative soft-tissue release, postoperative incision inflammation, incidence of DVT, incidence of deep infection, and ROM at day 90 after THR was found in the two groups (P > 0.05). Conclusions: The application of hemocoagulase combined with PRP in THR can reduce perioperative blood loss, increase wound healing speed and quality, and improve coagulation and immune function. It is a safe and effective method for the patients with knee osteoarthritis who underwent THR.

Biopsy-tract haemocoagulase injection reduces major complications after CT-guided percutaneous transthoracic lung biopsy.

AIM: To determine whether the injection of haemocoagulase into the biopsy tract can reduce pneumothorax and pulmonary haemorrhage after computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTLB). MATERIALS AND METHODS: A retrospective study was performed involving patients with undiagnosed pulmonary lesions scheduled for PTLB between January 2020 and March 2021. Patients were assigned to the haemocoagulase group or the non-haemocoagulase group. After CT-guided biopsies were performed with a 17 G coaxial system, patients in the haemocoagulase group received a haemocoagulase injection (0.2-0.5 units) in the biopsy tract as the sheath was withdrawn. Postoperative image studies were performed to evaluate complications, including pneumothorax and pulmonary haemorrhage. Factors, including the patient's position, lesion location, and pathological results, were evaluated to determine their associations with the complications. RESULTS: A total of 100 patients were included, with 44 men and a mean age of 53 years old. The overall incidences of pneumothorax and pulmonary haemorrhage were 15% and 13%, respectively. The incidences of pneumothorax and pulmonary haemorrhage were statistically significantly lower in the haemocoagulase group (8% and 6%, respectively) than in the non-haemocoagulase group (22% and 20%, respectively; p=0.04 and 0.03, respectively). There was no statistically significant difference in haemoptysis between the haemocoagulase (6%) and non-haemocoagulase (2%) groups (p=0.23). There were also no statistically significant associations of pneumothorax or pulmonary haemorrhage with the patients' positions, lesion location, or pathological results. CONCLUSION: Biopsy tract haemocoagulase injection reduced the incidences of postoperative pneumothorax and pulmonary haemorrhage after PTLB.

A prospective comparison of four methods for preventing pacemaker pocket infections.

This study aims to evaluate four pacemaker pocket cleaning methods for preventing implantation-related infections. This single-center trial prospectively randomized 910 patients undergoing first-time pacemaker implantation or replacement into four pocket cleaning methods: hemocoagulase (group A, n = 228), gentamicin (group B, n = 228), hemocoagulase plus gentamicin (group C, n = 227), and normal saline (group D, n = 227). Before implanting the pacemaker battery, the pockets were cleaned with gauze presoaked in the respective cleaning solutions. Then, these patients were followed up to monitor the occurrence of infections for 1 month after implantation. Twelve implantation-related infections occurred in 910 patients (1.32%): four patients from group A (1.75%), three patients from group B (1.32%), two patients from group C (0.88%), and three patients from group D (1.32%) (P > .05). Furthermore, two patients developed bloodstream infections (0.22%), and both of these patients were associated with pocket infection (one patient was from group A, while the other patient was from group C, respectively). No cases of infective endocarditis occurred. The differences in the number of infections in these study groups were not statistically significant. The application of hemocoagulase, gentamicin, hemocoagulase plus gentamicin, or normal saline on the presoaked gauze before implantation was equally effective in preventing pocket-associated infections.

A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study.

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 106 or 2 × 106 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 µL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.

[Effect of hemocoagulase agkistrodon on coagulation status in patients with traumatic brain injury in vitro].

Objective: To analyze the effects of hemocoagulase agkistrodon (HCA) on the coagulation status of healthy people and traumatic brain injury (TBI) patients in vitro. Methods: A total of 10 TBI patients were enrolled from December 2018 to June 2019,and 24 age and sex matched healthy controls were also enrolled. Clinical and pathological data, blood samples of all subjects were collected. Different gradient concentrations of HCA were added to the blood samples which were detected by thromboelastography, and the R value, K value, α angle and MA value of thromboelastography parameters between the two groups were analyzed to explore the effect of HCA on the coagulation status of patients with TBI. Results: With the increase of HCA concentration in blood samples, the R and K values gradually increased, and the α angles and MA values gradually decreased in both TBI patients group which included 7 males and 3 females, with an median age of 33 (28-39) years old and healthy control group which included 11 males and 13 females, with an median age of 33 (23-49) years old. The differences in the R values, K values, α angles, and MA values of different concentration gradients were statistically significant in both healthy control group and TBI patients group (χ2 were 109.80, 131.28, 185.47, 165.97 and 54.92, 75.60, 80.12, 59.25, respectively, all P<0.001). The differences between R values after adding HCA of 0-0.105 U/ml in the healthy group were statistically significant (P=0.025), but K values, α angles and MA values were not statistically significant (P values were 0.275, 0.206 and 0.330, respectively); the R values of the TBI patients group were not statistically significant after adding HCA of 0 to 0.105 U/ml (P=0.976), and the K values, α angles, and MA values were statistically significant (P values were 0.047, 0.041, and 0.034, respectively).The R values of the healthy control group, the TBI patients group, and the overall data were significantly positively correlated with the HCA dose (r values were 0.552、0.700、0.420, respectively, P<0.001), the K values were significantly positively correlated with the HCA dose (r values were 0.726、0.861、0.750, respectively, P<0.001), the α angles were significantly negatively correlated with the HCA dose (r values were -0.815、-0.876、-0.807, respectively, P<0.001) and the MA values were significantly negatively correlated with the HCA dose (r values were -0.757、-0.710、-0.729, respectively, P<0.001). Conclusions: HCA does not aggravate the procoagulant state of blood in healthy people and TBI patients, and with the increase of HCA concentration in blood, the blood samples of both groups show a tendency to decrease the coagulation ability.

Hemocoagulase agkistrodon can prevent bleeding and induce hypofibrinogenemia in hepatic disease cases
.

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.

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.

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.

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.

Hemostatic Effect of Hemocoagulase Agkistrodon on Surgical Wound in Breast Cancer Surgery.

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.

Hemocoagulase agkistrodon-induced anaphylactic shock: A case report and literature review.

Hemocoagulase agkistrodon for injection is the national first-class new drug of China with good hemostatic function and safety for capillary hemorrhage in abdominal incision of surgical patients. Adverse drug reactions (ADRs) to hemocoagulase agkistrodon are rarely reported. In this paper, we describe a case of a 41-year-old woman who developed anaphylactic shock attributed to hemocoagulase agkistrodon before colon cancer surgery. Based on the Naranjo ADR probability score, a "probable" cause and effect relationship existed for this case. Although the cause of anaphylactic reaction (hemocoagulase or excipient) and exact mechanism of hemocoagulase agkistrodon-induced anaphylactic reaction are unknown, attention should be drawn to potential ADRs in clinical use.

Avoiding unnecessary blood transfusions in women with profound anaemia.

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.

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.

Batroxobin binds fibrin with higher affinity and promotes clot expansion to a greater extent than thrombin.

Batroxobin is a thrombin-like serine protease from the venom of Bothrops atrox moojeni that clots fibrinogen. In contrast to thrombin, which releases fibrinopeptide A and B from the NH2-terminal domains of the Aα- and Bß-chains of fibrinogen, respectively, batroxobin only releases fibrinopeptide A. Because the mechanism responsible for these differences is unknown, we compared the interactions of batroxobin and thrombin with the predominant γA/γA isoform of fibrin(ogen) and the γA/γ' variant with an extended γ-chain. Thrombin binds to the γ'-chain and forms a higher affinity interaction with γA/γ'-fibrin(ogen) than γA/γA-fibrin(ogen). In contrast, batroxobin binds both fibrin(ogen) isoforms with similar high affinity (Kd values of about 0.5 µM) even though it does not interact with the γ'-chain. The batroxobin-binding sites on fibrin(ogen) only partially overlap with those of thrombin because thrombin attenuates, but does not abrogate, the interaction of γA/γA-fibrinogen with batroxobin. Furthermore, although both thrombin and batroxobin bind to the central E-region of fibrinogen with a Kd value of 2-5 µM, the α(17-51) and Bß(1-42) regions bind thrombin but not batroxobin. Once bound to fibrin, the capacity of batroxobin to promote fibrin accretion is 18-fold greater than that of thrombin, a finding that may explain the microvascular thrombosis that complicates envenomation by B. atrox moojeni. Therefore, batroxobin binds fibrin(ogen) in a manner distinct from thrombin, which may contribute to its higher affinity interaction, selective fibrinopeptide A release, and prothrombotic properties.

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.

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.