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AIMS: The objective of this study was to evaluate the effectiveness of batroxobin in improving functional outcomes and reducing stroke recurrence among patients with acute ischemic stroke beyond the therapeutic time window for thrombolytic therapy. METHODS: This multicenter, retrospective study enrolled 492 patients with acute moderate-to-severe ischemic stroke within 24 h. 238 patients were given standard (basic) therapy. On the basis of standard treatment, 254 patients received an initial intravenous infusion of batroxobin 10 U on day 1, followed by subsequent infusions of batroxobin 5 U on the 3rd and 5th days, respectively. RESULTS: In the batroxobin group, 8.3% of patients experienced recurrence stroke, compared to 17.2% in the control group (HR, 0.433; 95% CI, 0.248 to 0.757; p = 0.003). Furthermore, intravenous batroxobin significantly improved the distribution of 90-120 day disability. Moderate-to-severe bleeding events were reported in three patients (1.2%) in the batroxobin group and one patient (0.4%) in the control group (p = 0.369). CONCLUSIONS: Among patients with acute moderate-to-severe ischemic stroke beyond the time window for thrombolytic therapy, treatment with intravenous batroxobin had a lower risk of stroke recurrence and a better recovery of function outcome without increasing bleeding events. Prospective studies are needed to further confirm.
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Batroxobina , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Batroxobina/uso terapéutico , Batroxobina/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND AND PURPOSE: More evidence supports the benefits of batroxobin combined with anticoagulation in correcting acute cerebral venous thrombosis (CVT). The dynamic fluctuations of peripheral blood platelets, fibrinolysis, and coagulation biomarkers during this therapy were analyzed. METHODS: We investigated batroxobin's effects on the antithrombotic system under two regimens. The pretreatment group included patients on anticoagulants for at least 1 week before starting batroxobin. The simultaneous treatment group began both treatments upon admission. The control group received only anticoagulation. Batroxobin was given on alternate days at doses of 10BU, 5BU, and 5BU, totaling three doses. Anticoagulation was continuous. Baseline data were T0; the next day after each batroxobin dose was T1, T2, and T3. Data from these four time points was analyzed. RESULTS: The time-point paired sample T-test results of the pretreatment group [n = 60; mean age (SD), 43.3(16.5); 38 (63.35%) women] showed that batroxobin significantly inhibited ADP-induced platelet aggregation rate (T1-T0: p = 0.015; T2-T0: p = 0.025; T3-T0: p = 0.013), decreased fibrinogen level (T1-T0: p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), and increased D-dimer (T1-T0:p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), TT (T1-T0:p = 0.046; T2-T0: p = 0.003; T3-T0: p < 0.001), and APTT (T1-T0:p = 0.021; T2-T0: p = 0.012; T3-T0: p = 0.026). Compared to the control group, the simultaneous treatment group showed significantly higher TT (T2: p = 0.002; T3: p = 0.004) and D-dimer (T1: p < 0.001; T2: p < 0.001; T3: p < 0.001) values, while fibrinogen (T2: p < 0.001; T3: p < 0.001) levels were significantly lower. Using batroxobin can alleviate the amplitude of changes in coagulation indicators other than TT caused by anticoagulants. The above conclusions are consistent with the results of repeated measurement data analysis. CONCLUSIONS: Batroxobin can significantly inhibit ADP-induced platelet aggregation rate, increase D-dimer, decrease fibrinogen, and prolong TT and APTT in the presence of anticoagulant agents. Using batroxobin can reduce the amplitude of changes in coagulation indicators caused by anticoagulants. These results reveal the potential mechanism of batroxobin combined with anticoagulation in the safe and effective treatment of CVT.
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Batroxobina , Trombosis Intracraneal , Trombosis de la Vena , Humanos , Batroxobina/farmacología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Trombosis Intracraneal/tratamiento farmacológico , Trombosis Intracraneal/sangre , Trombosis de la Vena/tratamiento farmacológico , Fibrinolíticos/farmacología , Fibrinolíticos/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Anciano , Plaquetas/efectos de los fármacos , Plaquetas/metabolismoRESUMEN
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.
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Administración Tópica , Antifibrinolíticos , Axila , Neoplasias de la Mama , Drenaje , Escisión del Ganglio Linfático , Ácido Tranexámico , Humanos , Femenino , Ácido Tranexámico/administración & dosificación , Ácido Tranexámico/uso terapéutico , Neoplasias de la Mama/cirugía , Persona de Mediana Edad , Método Doble Ciego , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/uso terapéutico , Drenaje/métodos , Adulto , Batroxobina/administración & dosificación , Batroxobina/uso terapéutico , Seroma/prevención & control , Seroma/etiología , Anciano , Resultado del Tratamiento , Atención Perioperativa/métodos , Hemostáticos/administración & dosificación , Hemostáticos/uso terapéuticoRESUMEN
The objective of this study was to explore the real-world incidence, severity, clinical features, and potential risk factors associated with hypofibrinogenemia induced by hemocoagulase. Based on Chinese Hospital Pharmacovigilance System, a retrospective case-control study was conducted, enrolling hospitalized patients who received hemocoagulase for the treatment or prevention of hemorrhage in Weifang People's Hospital in China from January 2021 to May 2022. Univariate and multivariate logistic regression was performed to analyze the potential risk factors. Out of 10,397 hospitalized patients who received hemocoagulase, 341 patients showed positive triggers, with 235 patients ultimately conformed as hemocoagulase-associated hypofibrinogenemia. The system positive alarm rate was 68.91%, and the overall incidence of hemocoagulase-induced hypofibrinogenemia was 2.26%, predominantly characterized by mild to moderate severity levels. The incidence varied among the 4 types of hemocoagulase, with the highest incidence observed in hemocoagulase Agkistrodon Halys Pallas at 4.59%. The incidence of hemocoagulase from Deinagkistrodon acutus, Bothrops Atrox and Adder were 0.97%, 0.44% and 0.12%, respectively. Multivariate logistic regression analysis revealed that age (odds ratios [OR]â =â 177.328, Pâ <â .001), source of snake venom (ORâ =â 5.641, Pâ <â .05), albumin (ORâ =â 2.487, Pâ <â .001), and cumulative dosage (ORâ =â 1.106, Pâ <â .001) were independent risk factors. Increased risk of hemocoagulase-related hypofibrinogenemia may be associated with children, elderly patients, low albumin levels, high cumulative doses and hemocoagulase from Agkistrodon Halys Pallas. Early recognition and close drug monitoring for these high-risk patients are vital in clinical practice.
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Afibrinogenemia , Crotalinae , Serpientes Venenosas , Niño , Anciano , Animales , Humanos , Estudios Retrospectivos , Estudios de Casos y Controles , Batroxobina , Incidencia , Albúminas , Factores de RiesgoRESUMEN
OBJECTIVE: To investigate the effects of combination therapy with and without batroxobin, and the frequency of batroxobin use on the prognosis of profound sudden sensorineural hearing loss. METHODS: Hearing recovery in the batroxobin group (231 patients) and non-batroxobin group (56 patients) was compared. The correlation between the number of times batroxobin was used and hearing recovery was analysed. RESULTS: The decrease in hearing threshold and overall improvement rate in the batroxobin group with hearing loss exceeding 100 dB HL was significantly higher than that in the non-batroxobin group. There was no linear correlation between the number of times batroxobin was used and the overall improvement rate. Using batroxobin two to three times achieved a therapeutic effectiveness plateau. CONCLUSION: Batroxobin can improve the efficacy of combination therapy for profound sudden sensorineural hearing loss exceeding 100 dB HL, and using batroxobin two to three times yields the maximum overall improvement rate.
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Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Humanos , Batroxobina/uso terapéutico , Batroxobina/farmacología , Resultado del Tratamiento , Pérdida Auditiva Súbita/tratamiento farmacológico , Pérdida Auditiva Sensorineural/tratamiento farmacológico , AudiciónRESUMEN
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.
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Bothrops , Hemostáticos , Animales , Humanos , Batroxobina/efectos adversos , Batroxobina/uso terapéutico , Colon , Hemostasis , Hemostáticos/efectos adversos , Hemostáticos/uso terapéuticoRESUMEN
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.
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Fracturas de Cadera , Ácido Tranexámico , Humanos , Batroxobina , Ácido Tranexámico/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Periodo Perioperatorio , Fémur , Fracturas de Cadera/cirugíaRESUMEN
The Rationale: Glanzmann thrombasthenia is a rare platelet disorder affecting 0.0001% of the population. Dentists may often be unaware of this condition, and manipulation of soft tissue can lead to grave consequences, which may even result in fatality. Patient Concerns: In this case report, a 4-year-old patient with Glanzmann thrombasthenia reported to the department with a chief complaint of a discoloured tooth. Clinical Findings: On examination, 51 was nonvital, and pulpectomy was the treatment planned. The non-vital anterior tooth was treated with a pulpectomy procedure. There was uncontrolled bleeding during the procedure. Treatment: A topical solution of BotroClot was used to arrest the bleeding, and obturation was completed following that. The post-operative period was uneventful. Take-away Lessons: Case report explored the use of a topical hemostatic agent to arrest bleeding from the canal. This case report warrants eliciting a thorough medical history before any dental procedure.
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Hemostáticos , Trombastenia , Batroxobina , Preescolar , Hemorragia/etiología , Hemostáticos/uso terapéutico , Humanos , Trombastenia/complicaciones , Trombastenia/diagnóstico , Diente PrimarioRESUMEN
Snake venom thrombin drugs are hemostatic drugs prepared from Agkistrodon halys venom, and the main active ingredients are snake venom thrombin-like enzymes (svTLEs). The svTLEs derived from different snake species differ in their structures, hemostatic mechanisms, and pharmacological effects. Therefore, accurate identification of the source of snake venom species and determination of the svTLE content are essential to ensure the quality of these products. Based on proteomics technology, the marker peptides of svTLEs from Bothrops atrox were screened with species specificity for the first time in this study, and an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for species identification and determination of the svTLE content of Bothrops atrox was established. After reductive alkylation and trypsin enzymolysis of the purified svTLE from Bothrops atrox, enzymatic peptide fragments were obtained and determined by easy-nano liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (Nano LC-Q-Exactive-MS). The mass spectrum data were analyzed by Proteome Discoverer 2.2 software. The maker peptide "EAYNGLPAK", which characterized the svTLE from Bothrops atrox, was finally screened and validated by comparison of the basic local alignment search tool (BLAST) with the NCBI and UniProt databases. For the marker peptide, the enzymolysis temperature, enzymolysis time and amount of enzyme for the sample preparation were optimized. The optimized enzymolysis conditions were as follows: enzymolysis temperature, 37 â; enzymolysis time, 4 h; and amount of enzyme, 10 µL. A qualitative and quantitative detection method based on UHPLC-MS/MS was established by optimizing the chromatographic and mass spectrometric conditions. Accordingly, 20 mg of the evenly mixed sample was weighed and placed in a 100 mL volumetric flask. Then, 25 mmol/L ammonium bicarbonate solution was added to dissolve the sample, and the solution was diluted to the scale. Precisely 1.00 mL of the solution was extracted; subsequently, addition of 10 µL trypsin solution was added, followed by shaking, and the mixture was placed in an incubator for 4 h to induce enzymolysis at a constant temperature of 37 â. The mixture was subsequently removed from the incubator, cooled to ambient temperature, centrifuged at 12000 r/min for 10 min, and analyzed by LC-MS. Separation was performed on the UPLC system with a Thermo Hypersil GOLD C18 column (100 mm×2.1 mm, 3.0 µm) under the gradient elution of acetonitrile containing 0.1% (v/v) acetic acid and water containing 0.1%(v/v) acetic acid, at a flow rate of 0.3 mL/min, column temperature of 30 â, and injection volume of 2 µL. The maker peptides were determined in the electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM) modes using the external standard curve method. The detection ions were m/z 481.9> 315.2 and 481.9> 485.2. There was a good linear relationship between the mass concentration of the marker peptide and the chromatographic peak area in the range of 2.5-30 ng/mL, and the correlation coefficient (r) was 0.9996, The limit of detection (S/N=3) and limit of quantification (S/N=10) were 2.5 mg/kg and 6.25 mg/kg, respectively. At spiked levels of 40, 80, and 120 mg/kg, the recoveries of the marker peptides were 95.5%-101.9%, while the relative standard deviations (RSDs) of the results for parallel analyses at various spiked levels were 1.1%-3.2%. The developed method is simple, rapid, sensitive, and specific, and it can be used for the identification of Bothrops atrox venom species and determination of the svTLE content. The findings of this study would help ensure the quality of hemocoagulase products from the relevant source and provide a reference for the quality control of other snake venom products.
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Bothrops , Hemostáticos , Acetonitrilos , Animales , Batroxobina , Cromatografía Líquida de Alta Presión , Fragmentos de Péptidos , Péptidos , Proteoma , Venenos de Serpiente , Espectrometría de Masas en Tándem/métodos , Trombina , Tripsina , AguaRESUMEN
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.
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Enfermedades Pulmonares , Neumotórax , Batroxobina , Femenino , Hemorragia/etiología , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/prevención & control , Masculino , Persona de Mediana Edad , Neumotórax/epidemiología , Neumotórax/etiología , Neumotórax/prevención & control , Radiografía Intervencional/métodos , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodosRESUMEN
Objectives: To compare the clinical outcomes of using different hemostatic agents after transurethral plasmakinetic resection of the prostate (TUPKP) in benign prostatic hyperplasia (BPH) patients. Methods: The patients were divided into 5 groups according to the hemostatic agents used after TUPKP, including the haemocoagulase agkistrodon for injection (HCA), hemocoagulase for injection (HC), hemocoagulase bothrops atrox for injection (HCB), ethylenediamine diaceturate injection (EDD), and tranexamic acid (TXA). Propensity score matching was performed based on age, body mass index, prostate volume, hypertension status, fasting blood glucose, smoking, and drinking history. The hospitalization time, bladder irrigation time, indwelling catheterization time, the patency of urine flow, and blood transfusion records were used as outcome indicators to compare the clinical effects of these five agents. Results: We finally matched 65 pairs receiving HCA or HC, 71 pairs receiving HCA or HCB, 38 pairs receiving HCA or TXA, and 29 pairs receiving HCA or EDD. Compared with HC, HCA given during the perioperative period significantly reduced the median hospitalization time [7.00 days (5.00, 8.00) vs. 9.00 days (8.00, 10.00); p < 0.001] and median catheterization time (109.00 hours [88.00, 129.00] vs. 164.00 hours [114.00, 189.00], p < 0.001). Compared with EDD, the median hospitalization time (7.00 days [6.00, 8.00] vs. 10.00 days [8.00, 11.00]; p < 0.001) and median catheterization time (113.00 hours [95.00, 143.00] vs. 160.00 hours [139.00, 168.00]; p < 0.001) were also significant shorter in HCA group. Compared with HCB, median bladder irrigation time (45.00 hours [27.00, 71.00] vs. 49.00 hours [45.00, 72.00]; p = 0.04) was shorter in the HCA group. However, there were no statistical differences in outcomes between HCA and TXA. Conclusions: HCA probably has an advantage over HC, HCB, and EDD in reducing the hospitalization time, catheterization time, and bladder irrigation time among BPH patients undergoing TUPKP.
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Agkistrodon , Hemostáticos , Hiperplasia Prostática , Resección Transuretral de la Próstata , Animales , Humanos , Masculino , Batroxobina , Puntaje de Propensión , Próstata , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/cirugíaRESUMEN
A percutaneous renal biopsy is an essential tool for the diagnosis of various renal diseases; however, post-biopsy bleeding is a major complication. Hemocoagulase is a detoxified and purified snake venom enzyme that is widely used to prevent post-procedural bleeding. In this study, we retrospectively analyzed the effect of hemocoagulase on post-renal biopsy bleeding. We included 221 patients who underwent percutaneous renal biopsy between April 2017 and December 2020 and analyzed post-renal biopsy hemoglobin (Hb) decline in patients who were administered a periprocedural hemocoagulase injection. After the renal biopsy, the mean Hb decrease in the entire patient cohort was 0.33 ± 0.84 g/dL. Periprocedural hemocoagulase injection lowered the Hb decline post-renal biopsy (0.50 ± 0.87 vs. 0.23 ± 0.80 g/dL, p = 0.0204). The propensity-matched cohort was also adjusted for factors influencing postprocedural bleeding; periprocedural hemocoagulase injection reduced the Hb decline post-renal biopsy (0.56 ± 0.89 vs. 0.17 ± 0.74 g/dL, p = 0.006). There were no adverse events (e.g., thrombosis and anaphylactic shock) due to hemocoagulase. Our study demonstrated the beneficial effect of hemocoagulase on post-renal biopsy Hb decline, suggesting its clinical value in preventing post-renal biopsy bleeding.
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Batroxobina , Hemorragia , Batroxobina/uso terapéutico , Batroxobina/toxicidad , Biopsia , Hemorragia/inducido químicamente , Humanos , Estudios RetrospectivosRESUMEN
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.
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Artroplastia de Reemplazo de Cadera , Plasma Rico en Plaquetas , Artroplastia de Reemplazo de Cadera/efectos adversos , Batroxobina , Humanos , Molécula 1 de Adhesión Intercelular , Factor de Necrosis Tumoral alfa , Factor de von WillebrandRESUMEN
INTRODUCTION: We identified a novel heterozygous AαE11del variant in a patient with congenital dysfibrinogenemia. This mutation is located in fibrinopeptide A (FpA). We analyzed the effect of AαE11del on the catalyzation of thrombin and batroxobin and simulated the stability of the complex structure between the FpA fragment (AαG6-V20) peptide and thrombin. MATERIALS AND METHODS: We performed fibrin polymerization and examined the kinetics of FpA release catalyzed by thrombin and batroxobin using purified plasma fibrinogen. To clarify the association between the AαE11 residue and thrombin, we calculated binding free energy using molecular dynamics simulation trajectories. RESULTS: Increasing the thrombin concentration improved release of FpA from the patient's fibrinogen to approximately 90%, compared to the previous 50% of that of normal fibrinogen. Fibrin polymerization of variant fibrinogen also improved. In addition, greater impairment of variant FpA release from the patient's fibrinogen was observed with thrombin than with batroxobin. Moreover, the calculated binding free energy showed that the FpA fragment-thrombin complex became unstable due to the missing AαE11 residue. CONCLUSIONS: Our findings indicate that the AαE11 residue is involved in FpA release in thrombin catalyzation more than in batroxobin catalyzation, and that the AαE11 residue stabilizes FpA fragment-thrombin complex formation.
Asunto(s)
Fibrinopéptido A/genética , Fibrinopéptido A/metabolismo , Eliminación de Secuencia , Trombina/metabolismo , Afibrinogenemia/sangre , Afibrinogenemia/genética , Afibrinogenemia/metabolismo , Batroxobina/metabolismo , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Análisis Mutacional de ADN , Fibrina/metabolismo , Fibrinopéptido A/química , Heterocigoto , Humanos , Cinética , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Unión Proteica , Conformación Proteica , Multimerización de Proteína , Relación Estructura-Actividad , Trombina/químicaRESUMEN
Recombinant batroxobin (S3101) is a thrombin-like serine protease that binds to fibrinogen or is taken up by the reticuloendothelial system. A literature survey showed no adequate method that could determine sufficient concentrations to evaluate pharmacokinetic parameters for phase I clinical studies. Therefore, a sensitive method is urgently needed to support the clinical pharmacokinetic evaluation of S3101. In this study, a sensitive bioanalytical method was developed and validated, using a Quanterix single molecular array (Simoa) assay. Moreover, to thoroughly assess the platform, enzyme-linked immunosorbent assay and electrochemiluminescence assay were also developed, and their performance was compared with that of this novel technology platform. The assay was validated in compliance with the current guidelines. Measurements with the Simoa assay were precise and accurate, presenting a valid assay range from 6.55 to 4000 pg/mL. The intra- and inter-run accuracy and precision were within -19.3% to 15.3% and 5.5% to 17.0%, respectively. S3101 was stable in human serum for 280 days at -20°C and -70°C, for 2 h prior to pre-treatment and 24 h post pre-treatment at room temperature (22°C-28°C), respectively, and after five and two freeze-thaw cycles at -70°C and -20°C, respectively. The Simoa assay also demonstrated sufficient dilution linearity, assay sensitivity, and parallelism for quantifying S3101 in human serum. The Simoa assay is a sensitive and adequate method for evaluating the pharmacokinetic parameters of S3101 in human serum.
Asunto(s)
Batroxobina/sangre , Ensayo de Inmunoadsorción Enzimática , Proteínas Recombinantes/sangre , Batroxobina/aislamiento & purificación , Batroxobina/farmacocinética , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Unión Proteica/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacocinéticaRESUMEN
OBJECTIVE: This study aimed to evaluate the efficacy and safety of using Hemocoagulase Bothrops Atrox in the submucosal injection solution for endoscopic submucosal dissection (ESD). METHODS: A total of 120 patients with superficial neoplastic lesions of the esophagus, stomach, and colon receiving ESD were randomly divided into two groups: The epinephrine group used epinephrine-containing submucosal fluid cushion for ESD, while the hemocoagulase group used Hemocoagulase Bothrops Atrox-containing submucosal fluid cushion for ESD. The preoperative, intraoperative, and postoperative clinical parameters and postoperative adverse events of the two groups were recorded, and comparative analysis within and between groups was performed. RESULTS: There was no significant difference in the demographic and clinical characteristics between the hemocoagulase and epinephrine group (all P > 0.05). ESD surgery was completed in all patients. The hemocoagulase group had significantly shorter surgery time (P = 0.003) and less number of intraoperative bleeding (P = 0.010) than the epinephrine group. However, there was no significant difference in the incidences of postoperative delayed hemorrhage, and adverse events between the two groups (all P > 0.05). Multivariate linear regression demonstrated that the epinephrine group had significantly more number of intraoperative bleeding (B: 0.98, 95% confidence interval: 0.04-1.93) as compared with the hemocoagulase group. CONCLUSION: Compared with epinephrine, using Hemocoagulase Bothrops Atrox in the submucosal injection for ESD surgery can significantly reduce the number of intraoperative bleeding, shorten the operation time, and did not elevate the incidence of adverse events.
Asunto(s)
Bothrops , Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Animales , Batroxobina/efectos adversos , Resección Endoscópica de la Mucosa/efectos adversos , Epinefrina/efectos adversos , Humanos , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
Uncontrolled bleeding associated with trauma and surgery is the leading cause of preventable death. Batroxobin, a snake venom-derived thrombin-like serine protease, has been shown to clot fibrinogen by cleaving fibrinopeptide A in a manner distinctly different from thrombin, even in the presence of heparin. The biochemical properties of batroxobin and its effect on coagulation have been well characterized in vitro. However, the efficacy of batroxobin on hemostatic clot formation in vivo is not well studied due to the lack of reliable in vivo hemostasis models. Here, we studied the efficacy of batroxobin and slounase, a batroxobin containing activated factor X, on hemostatic clot composition and bleeding using intravital microcopy laser ablation hemostasis models in micro and macro vessels and liver puncture hemostasis models in normal and heparin-induced hypocoagulant mice. We found that prophylactic treatment in wild-type mice with batroxobin, slounase and activated factor X significantly enhanced platelet-rich fibrin clot formation following vascular injury. In heparin-treated mice, batroxobin treatment resulted in detectable fibrin formation and a modest increase in hemostatic clot size, while activated factor X had no effect. In contrast, slounase treatment significantly enhanced both platelet recruitment and fibrin formation, forming a stable clot and shortening bleeding time and blood loss in wild-type and heparin-treated hypocoagulant mice. Our data demonstrate that, while batroxobin enhances fibrin formation, slounase was able to enhance hemostasis in normal mice and restore hemostasis in hypocoagulant conditions via the enhancement of fibrin formation and platelet activation, indicating that slounase is more effective in controlling hemorrhage.
Asunto(s)
Batroxobina/uso terapéutico , Pruebas de Coagulación Sanguínea/métodos , Coagulación Sanguínea/efectos de los fármacos , Hemorragia/tratamiento farmacológico , Hemostáticos/uso terapéutico , Animales , Batroxobina/farmacología , Hemostáticos/farmacología , Humanos , Masculino , RatonesRESUMEN
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.
Asunto(s)
Ácido Hialurónico/farmacología , Degeneración del Disco Intervertebral/terapia , Disco Intervertebral/trasplante , Queratina-19/genética , Trasplante de Células Madre Mesenquimatosas , Animales , Batroxobina/farmacología , Bovinos , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ácido Hialurónico/química , Hidrogeles/química , Hidrogeles/farmacología , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/patología , Células Madre Mesenquimatosas/citología , Núcleo Pulposo/crecimiento & desarrollo , Núcleo Pulposo/trasplante , Técnicas de Cultivo de Órganos , Plasma Rico en Plaquetas/químicaRESUMEN
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 0.552ã0.700ã0.420, respectively, P<0.001), the K values were significantly positively correlated with the HCA dose (r values were 0.726ã0.861ã0.750, respectively, P<0.001), the α angles were significantly negatively correlated with the HCA dose (r values were -0.815ã-0.876ã-0.807, respectively, P<0.001) and the MA values were significantly negatively correlated with the HCA dose (r values were -0.757ã-0.710ã-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.
Asunto(s)
Agkistrodon , Lesiones Traumáticas del Encéfalo , Adulto , Animales , Batroxobina , Coagulación Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , TromboelastografíaRESUMEN
RATIONAL: Hemocoagulase, a hemostatic, is used in patients with trauma, gastrointestinal bleeding, or pulmonary hemorrhage or those undergoing surgery. However, paradoxical bleeding after hemocoagulase administration is not considered a clinically significant adverse effect. Here, we report a case of paradoxical pulmonary hemorrhage associated with hypofibrinogenemia after administration of the hemocoagulase batroxobin in a patient with hemoptysis. PATIENT CONCERNS: An 86-year-old woman complained of hemoptysis during hospitalization with organophosphate poisoning. Hemocoagulase was administered to manage bleeding; however, bleeding signs, such as hemoptysis, massive epistaxis, and ecchymosis, recurred. DIAGNOSES: The patient was diagnosed with acquired hypofibrinogenemia on the basis of the reduced plasma fibrinogen level after hemocoagulase administration and lack of other causes of bleeding. INTERVENTION: Hemocoagulase administration was discontinued, and fibrinogen-containing plasma products were administered. OUTCOMES: The plasma fibrinogen level normalized and bleeding signs did not recur. LESSONS: It is necessary to measure plasma fibrinogen levels regularly in patients undergoing hemocoagulase administration and discontinue its administration when acquired hypofibrinogenemia is detected.