The Critical Blood-Sparing Effect of Tranexamic Acid (TXA) in Liposuction: A Systematic Review and Meta-Analysis.

Introduction: Tranexamic acid (TXA) has been used to improve bleeding outcomes in many surgical procedures. However, its blood-sparing effect in liposuction is not well established. Methods: A systematic literature search was performed using PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central, ClinicalTrials.gov, and WorldWideScience.org databases from their inception to October 8, 2021, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors focused on 3 main topics: 1) TXA, 2) liposuction, and 3) complications. We included articles evaluating the potential blood-sparing effects of TXA in liposuction. Studies were excluded if they were systematic review articles or protocol papers, animal studies, conference abstracts, survey studies, or non-English publications. Results: A total of 711 articles were identified, with 1 retrospective and 4 prospective (3 randomized) studies meeting our inclusion criteria. TXA was used in various forms: administered intravenously either on induction or after the procedure, mixed into the tumescent solution, or infiltrated into the liposuction sites after lipoaspiration. A significantly smaller reduction in hematocrit was noted in the TXA group compared with that in the non-TXA group (p<0.001) despite a significantly greater amount of lipoaspirate removed in the TXA group (p<0.001). Patients in non-TXA cohorts experienced adverse effects (such as seroma and need for transfusion) that were not seen in TXA cohorts. Conclusion: TXA use in patients undergoing liposuction seems to be associated with a beneficial blood-sparing effect, which may enhance safety in this population. Future studies should aim to determine the optimal route and dosing for TXA in liposuction. Evidence Based Medicine: Level IV.

Tranexamic acid reduces perioperative blood loss and postoperative hemoglobin loss during total ankle arthroplasty: A systematic review and meta-analysis of clinical comparative studies.

IMPORTANCE: Peri-operative blood loss during joint replacement procedures is a modifiable risk factor that impacts wound complications, hospital stay and total costs. Tranexamic acid (TXA) is an anti-fibrinolytic that has been widely used in orthopedic surgery, but its efficacy in the setting of total ankle arthroplasty (TAA) has not been quantified to date. AIM: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of administering TXA in patients undergoing TAA. EVIDENCE REVIEW: The Medline, Embase and Cochrane library databases were systematically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Five comparative studies examining blood loss following administration of TXA for patients undergoing TAA were included. The outcome measures of interest were blood loss, reduction in hemoglobin concentration, transfusion requirements, total complications and wound complications. FINDINGS: In total, 194 patients received TXA and 187 patients did not receive TXA while undergoing TAA. Based on the common-effects model for total blood loss for the TXA group versus control, the standardized mean difference (SMD) was -0.7832 (95% CI, -1.1544, -0.4120; P â€‹< â€‹0.0001), in favor of lower total blood loss for TXA. Based on the random-effects model for reduction in hemoglobin for the TXA group versus control, the SMD was -0.9548 (95% CI, -1.7850, -0.1246; P â€‹= â€‹0.0242) in favor of lower hemoglobin loss for TXA. Based on the random-effects model for total complications for the TXA group versus control, the risk ratio was 0.512 (95% CI, 0.1588, 1.6512; P â€‹= â€‹0.1876), in favor of lower total complications for TXA but this was not statistically significant. CONCLUSIONS: This current review demonstrated that administration of TXA led to a reduction in blood loss and hemoglobin loss without an increased risk of the development of venous thromboembolism in patients undergoing TAA. No difference was observed with respect to total complication rates between the TXA cohort and the control group. TXA appears to be an effective hemostatic agent in the setting of TAA, but further studies are necessary to identify the optimal timing, dosage and route of TXA during TAA. LEVEL OF EVIDENCE: III.

Tranexamic acid in patients with traumatic brain injury: a meta-analysis.

BACKGROUND: We performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). METHODS: We searched the literature for articles evaluating the effectiveness and safety of tranexamic acid (TXA) in TBI published between January 2012 and January 2021, and identified 8 studies with a total of 10860 patients: 5660 received TXA and 5200 served as controls. We used a dichotomous or continuous approach with a random or fixed-effect model to assess the efficacy and safety of TXA in TBI, and calculated the mean difference (MD) and odds ratio (OR) with the corresponding 95% confidence interval. RESULTS: In patients with TBI, early administration of TXA was associated with a greater relative benefit (MD -2.45; 95% CI = -4.78 to -0.12; p=0.04) and less total haematoma expansion (MD - 2.52; 95% CI = -4.85 to -0.19; p=0.03) compared to controls. There were no statistically significant differences in mortality (OR 0.94; 95% CI=0.85-1.03; p=0.18), presence of progressive haemorrhage (OR 0.75; 95% CI=0.56-1.01; p=0.06), need for neurosurgery (OR 1.15; 95% CI=0.66-1.98; p=0.63), high Disability Rating Scale score (OR 0.90; 95% CI=0.56-1.45; p=0.68), and incidence of ischaemic or thromboembolic complications (OR 1.34; 95% CI=0.33-5.46; p=0.68) between TBI patients treated with TXA and controls. CONCLUSIONS: Early administration of TXA in TBI patients may have a greater relative benefit and may inhibit haematoma expansion. There were no significant differences in mortality, presence of progressive haemorrhage, need for neurosurgery, high Disability Rating Scale score, and incidence of ischaemic or thromboembolic complications between TBI patients treated with TXA and controls. Further studies are needed to validate these results.

Role of Tranexamic Acid in Palliative Control of Bleeding in End-Stage Head and Neck Cancer: A Case Report.

Tumor-related bleeding is a common manifestation of end-stage head and neck cancer, and it can have a significant impact on a patient's quality of life. Tranexamic acid is an anti-fibrinolytic agent that has been shown to effectively control bleeding and reduce the need for transfusions in various hemorrhagic conditions. Here, we present the case of a patient with end-stage head and neck cancer experiencing recurrent episodes of bleeding, who was able to successfully achieve hemostasis after being treated with tranexamic acid. This case report highlights the role of tranexamic acid as a palliation agent that can help control the unpleasant bleeding symptoms of end-stage head and neck cancer and provide a better quality of life for patients.

Oral Tranexamic Acid for the Treatment of Melasma: Evidence and Experience-Based Consensus Statement from Indian Experts.

Melasma, a chronic pigmentary skin condition mainly affecting the face, remains a challenge despite the availability of several options for treatment. Many melasma patients are not satisfied with treatment outcomes. Tranexamic acid (TXA), an anti-fibrinolytic drug has shown promising results in patients with melasma. Evidence from several clinical studies has surfaced on efficacy and tolerability of TXA in these patients. It can be used as monotherapy or adjuvant with other therapies. Currently, there is no published consensus or guideline document for its use in the treatment of melasma. TXA is available for oral use, topical use as well as an injection. In this article, a consensus of Indian experts is prepared based on the available literature and experience with use of oral TXA in melasma. This review article might help clinicians for use of oral TXA appropriately while treating melasma.

Updated Clinical Review: Perioperative Use of Tranexamic Acid in Orthopedics and Other Surgeries.

Tranexamic acid is a well-known antifibrinolytic that has numerous clinical indications, and it is efficacious and safe in many perioperative scenarios including patients with some thrombotic risks. However, further studies that characterize clinical outcomes concerning dosing, timing, and routes in combination are needed in ultra high-risk populations.

Efficacy and Safety of Tranexamic Acid in Cancer Surgery. An Update of Clinical Findings and Ongoing Research.

In cancer patients undergoing surgery, tumor biology and anticancer treatments can increase the risk of perioperative bleeding and blood transfusions. Notably, blood transfusions can be potentially associated with an increased risk of life-threatening immune responses, acute lung injury, postoperative infections, and thromboembolism. Moreover, the link between perioperative transfusion and increased risk of cancer recurrence cannot be excluded. On the other hand, cancer patients have an increased risk of thromboembolism due to cancer itself and antineoplastic systemic treatments including chemotherapy and anti-angiogenic drugs. In this complex scenario, effective and safe strategies aimed at the prevention of blood transfusions are warranted. This narrative review addresses the efficacy, and the safety of the synthetic antifibrinolytic agent tranexamic acid (TXA) when used perioperatively in cancer surgery. Although in not oncologic surgery the use of TXA has been extensively studied, in the setting of cancer patients requiring surgery, the evidence is scarce. An overview of the ongoing clinical research is also provided.

Dual function of a bumblebee (Bombus ignitus) serine protease inhibitor that acts as a microbicidal peptide and anti-fibrinolytic venom toxin.

In bee venoms, low-molecular-weight peptides, including serine protease inhibitors (SPIs), exhibit multifunctional activities. Although SPIs in bee venoms are relatively well known, those that function in both the body and secreted venom of bees are not well-characterized. In this study, we identified a bumblebee (Bombus ignitus) SPI (BiSPI) that displays microbicidal and anti-fibrinolytic activities. BiSPI was found to consist of a trypsin inhibitor-like domain containing a P1 site and ten cysteine residues. We observed that the BiSPI gene was ubiquitously transcribed in the body, including the venom glands. In correlation, the BiSPI protein was detected both in the body and secreted venom by using an antibody against a recombinant BiSPI peptide produced in baculovirus-infected insect cells. Recombinant BiSPI exhibited inhibitory activity against trypsin but not chymotrypsin and inhibited microbial serine proteases and plasmin but not elastase or thrombin. Moreover, recombinant BiSPI recognized carbohydrates and bound to fungi and gram-negative and gram-positive bacteria. Consistent with these properties, recombinant BiSPI exhibited microbicidal activities against bacteria and fungi through induction of structural damage by binding to the microbial surfaces. Additionally, recombinant BiSPI inhibited the plasmin-mediated degradation of human fibrin and was thus concluded to exhibit anti-fibrinolytic activity. Moreover, the peptide showed no effect on hemolysis. These findings demonstrate the dual function of BiSPI, which acts as a microbicidal peptide and anti-fibrinolytic venom toxin.

THE USE OF ANTIFIBRINOLYTICS IN HIP TRAUMA SURGERY IN A PUBLIC HEALTH SYSTEM: A PROSPECTIVE STUDY.

OBJECTIVE: To evaluate the use of tranexamic acid (TXA) and ε-aminocaproic acid (EACA) in reducing blood loss in hip and proximal femur trauma surgery. METHODS: Prospective study with 49 patients surgically treated in a trauma hospital between Nov/2015 and Feb/2017. The patients were divided in two groups: TXA (n = 24) and EACA (n = 25). The comparison was made according to gender, age at the time of surgery, ASA, fracture and surgery type, estimated blood loss during surgical approach, hemoglobin and hematocrit levels pre and post-operative, and pharmacological cost. The data was processed using SPSS 22.0 with significance level of p < 0,05. RESULTS: No significant difference was found in the variables age, gender, ASA and estimated blood loss during surgical approach. No patient needed blood transfusion. When evaluated post-operatively, the hemoglobin and hematocrit values decrease had no significant difference between the antifibrinolytics (p > 0.05). When analyzing total cost for both pharmacological agents, higher cost was observed in EACA than in TXA (US$ 16.09 - US$ 2.73), resulting in a US$ 13.36 addition per patient. CONCLUSION: Antifibrinolytic use was efficient on lowering the total blood loss, without the need of blood transfusion. Level of evidence II, Prospective Comparative Study.

OBJETIVO: Avaliar o uso do ácido tranexâmico (ATX) e aminocapróico (AEAC) na redução da perda sanguínea em cirurgias para trauma do quadril e femur proximal. MÉTODOS: Estudo prospectivo com 49 pacientes operados em hospital de trauma entre nov./15 e fev./17. Pacientes divididos em dois grupos: ATX (n = 24) e AEAC (n = 25). Comparações feitas de acordo com o sexo, idade na cirurgia, ASA, tipo de fratura e cirurgia, perda sanguínea estimada durante a cirurgia, níveis de hemoglobina e hematócrito pré e pós-operatório e o custo das medicações. Dados processados no SPSS 22.0 com nível de significância de p < 0,05. RESULTADOS: Não foram encontradas diferenças significativas entre as seguintes variáveis: idade, sexo, ASA e perda sanguínea estimada durante a cirurgia. Nenhum paciente necessitou de transfusão sanguínea nos dois grupos. Na avaliação pós-operatória, não houve diferença significativa entre os grupos nos valores de queda da hemoglobina e hematócrito (p > 0,05). Analisando os custos de ambos as medicações, observou-se um custo mais elevado do AEAC em relação ao ATX (R$ 90,00 - R$ 15), resultando em R$ 75, 00 a mais por paciente. CONCLUSÃO: O uso dos antifibrinolíticos foi eficiente na redução da perda sanguínea, sem a necessidade de hemotransfusões. Nível de evidência II, Estudo Prospectivo Comparativo.

The use of antifibrinolytics in hip trauma surgery in a public health system: a prospective study / O uso de antifibrinolíticos em cirurgia de trauma de quadril em um serviço público de sáude: estudo prospectivo

ABSTRACT Objective: To evaluate the use of tranexamic acid (TXA) and ε-aminocaproic acid (EACA) in reducing blood loss in hip and proximal femur trauma surgery. Methods: Prospective study with 49 patients surgically treated in a trauma hospital between Nov/2015 and Feb/2017. The patients were divided in two groups: TXA (n = 24) and EACA (n = 25). The comparison was made according to gender, age at the time of surgery, ASA, fracture and surgery type, estimated blood loss during surgical approach, hemoglobin and hematocrit levels pre and post-operative, and pharmacological cost. The data was processed using SPSS 22.0 with significance level of p < 0,05. Results: No significant difference was found in the variables age, gender, ASA and estimated blood loss during surgical approach. No patient needed blood transfusion. When evaluated post-operatively, the hemoglobin and hematocrit values decrease had no significant difference between the antifibrinolytics (p > 0.05). When analyzing total cost for both pharmacological agents, higher cost was observed in EACA than in TXA (US$ 16.09 - US$ 2.73), resulting in a US$ 13.36 addition per patient. Conclusion: Antifibrinolytic use was efficient on lowering the total blood loss, without the need of blood transfusion. Level of evidence II, Prospective Comparative Study.

RESUMO Objetivo: Avaliar o uso do ácido tranexâmico (ATX) e aminocapróico (AEAC) na redução da perda sanguínea em cirurgias para trauma do quadril e femur proximal. Métodos: Estudo prospectivo com 49 pacientes operados em hospital de trauma entre nov./15 e fev./17. Pacientes divididos em dois grupos: ATX (n = 24) e AEAC (n = 25). Comparações feitas de acordo com o sexo, idade na cirurgia, ASA, tipo de fratura e cirurgia, perda sanguínea estimada durante a cirurgia, níveis de hemoglobina e hematócrito pré e pós-operatório e o custo das medicações. Dados processados no SPSS 22.0 com nível de significância de p < 0,05. Resultados: Não foram encontradas diferenças significativas entre as seguintes variáveis: idade, sexo, ASA e perda sanguínea estimada durante a cirurgia. Nenhum paciente necessitou de transfusão sanguínea nos dois grupos. Na avaliação pós-operatória, não houve diferença significativa entre os grupos nos valores de queda da hemoglobina e hematócrito (p > 0,05). Analisando os custos de ambos as medicações, observou-se um custo mais elevado do AEAC em relação ao ATX (R$ 90,00 - R$ 15), resultando em R$ 75, 00 a mais por paciente. Conclusão: O uso dos antifibrinolíticos foi eficiente na redução da perda sanguínea, sem a necessidade de hemotransfusões. Nível de evidência II, Estudo Prospectivo Comparativo.

Effects of intravenous tranexamic acid on ovarian reserve and intra-operative blood loss during laparoscopic cystectomy of endometriotic cyst: a pilot randomized controlled trial.

BACKGROUND: Strategies to preserve ovarian function after ovarian endometriotic cyst removal have been reported in many studies; however, no study has evaluated tranexamic acid administration during surgery. OBJECTIVE: To evaluate feasibility of conducting a definitive trial and assessing the potential efficacy of tranexamic acid on ovarian reserve and intra-operative blood loss by comparing mean differences in anti-Müllerian hormone (AMH) levels following laparoscopic ovarian cystectomy between tranexamic acid and control groups. MATERIALS AND METHODS: A parallel two-arm pilot trial was conducted with 40 participants with endometriotic cysts who underwent laparoscopic ovarian cystectomy. They were randomized 1:1 to either 1 g tranexamic acid (TXA) or no TXA (n = 20 per group). TXA was administered to the participants immediately after induction of general anesthesia and intubation. The primary outcome was the feasibility of conducting a definitive trial in terms of design and procedures (such as recruitment rate, retention, safety of intravenous 1 gm of TXA, sample size verification) and assess the efficacy of TXA on the ovarian reserve and intra-operative blood loss by comparing mean difference of AMH levels between TXA and control groups at pre- and 3 months post-surgery. RESULTS: The recruitment and successful completion rates were 95% and 100%. Baseline characteristics were similar in the two groups. The mean difference of serum AMH levels (pre- and 3 months post-surgery) between the TXA and control groups was not significantly different. When performing a subgroup analysis, the mean difference of AMH levels (pre- and 3 months post-surgery) seemed to be higher in the bilateral than in the unilateral ovarian cyst group but not significantly different. Operating time was significantly longer in bilateral than in unilateral cysts. No post-operative complications or adverse effects were found. CONCLUSION: The full randomized controlled trial for evaluating effects of TXA administration during laparoscopic cystectomy for endometrioma on ovarian reserve was shown to be feasible. Several modifications should be added for improving feasibility, for example, increasing the TXA dose, modifying TXA administration, focusing on either patients with unilateral or bilateral ovarian cysts, and exploring other outcome measures, e.g., surgeons' satisfaction. TRIAL REGISTRATION: Thai Clinical Trials Registry, TCTR20190424002 , Registered 24 April 2019.

Anti-fibrinolytic activity of a metalloprotease inhibitor from bumblebee (Bombus ignitus) venom.

Bee venom is a mixture of bioactive components that include proteases and protease inhibitors. A metalloprotease inhibitor has been predicted to be a bumblebee-specific toxin in the venom proteome of Bombus terrestris; however, the identification and functional roles of bee venom metalloprotease inhibitors have not been previously determined. In this study, we identified a bumblebee (B. ignitus) venom metalloprotease inhibitor (BiVMPI) that exhibits anti-fibrinolytic activity. BiVMPI contains a trypsin inhibitor-like cysteine-rich domain that exhibits similarity to inducible metalloprotease inhibitor. Using an anti-BiVMPI antibody raised against a recombinant BiVMPI protein produced in baculovirus-infected insect cells, the presence of BiVMPI in the venom gland and secreted venom of B. ignitus worker bees was confirmed. The recombinant BiVMPI protein demonstrated inhibitory activity against a metalloprotease, trypsin, chymotrypsin, protease K, and plasmin, but not subtilisin A, elastase, or thrombin. Additionally, the recombinant BiVMPI bound to plasmin and inhibited the plasmin-mediated degradation of fibrin, demonstrating an anti-fibrinolytic role for BiVMPI as a bee venom metalloprotease inhibitor. Our results provide the first evidence for the identification and anti-fibrinolytic activity of a metalloprotease inhibitor from bee venom.

Nebulized tranexamic acid for recurring hemoptysis in critically ill patients: case series.

BACKGROUND: Hemoptysis is a clinical condition encountered in the emergency department (ED) and must be managed and investigated urgently to maintain the patient's hemostasis. The management of hemoptysis depends on treating the underlying cause. Tranexamic acid (TXA) is an anti-fibrinolytic drug used to systemically control bleeding. There are a few studies available that investigate the use of nebulized tranexamic acid for hemoptysis with contradictory results. Our paper demonstrates three cases where patients presented with significant hemoptysis and had significant improvement in symptoms following the administration of nebulized tranexamic acid. The overall need for blood transfusion was reduced. RESULTS: Three patients presented to the emergency room for evaluation of hemoptysis. All three patients had different underlying pathologies resulting in their hemoptysis and were monitored in the ICU. Initial conventional medical therapies including the correction of coagulopathy and discontinuing offending agents were utilized for treatment. After persistent symptoms, nebulized TXA at a dose of 500 mg three times a day was administered. The patients were all discharged from the hospital with improvement in their symptoms. CONCLUSION: Tranexamic acid may be considered in the treatment of hemoptysis regardless of the underlying cause. This may be utilized pending further workup and investigation into the underlying source of the bleeding.

Preoperative tranexamic acid does not reduce transfusion rates in major oncologic surgery: Results of a randomized, double-blind, and placebo-controlled trial.

BACKGROUND AND OBJECTIVES: Allogeneic blood transfusions are associated with worse postoperative outcomes in oncologic surgery. The aim of this study was to introduce a preoperative intervention to reduce transfusion rates in this population. METHODS: Adult patients undergoing major oncologic surgery in five categories with similar transfusion rates were recruited. Enrollees received a single preoperative intravenous dose of placebo or tranexamic acid (1000 mg). The primary outcome measure was perioperative transfusion rate. Secondary outcome measures included: estimated blood loss, thromboembolic events, morbidity, hospital length of stay, and readmission rate. RESULTS: Seventy-six patients were enrolled, 39 in the tranexamic acid group and 37 in the placebo group, respectively. Demographics and surgery type were equivalent between groups. The transfusion rates were 8 out of 39 (20.5%) in the tranexamic acid group and 5 out of 37 (13.5%) in the placebo group, respectively (P = .418). Median estimated blood loss was 400 mL (interquartile range [IQR] = 150-600) in the tranexamic acid group compared with 300 mL (IQR = 150-800) in the placebo group (P = .983). There was one pulmonary embolism in each arm and no deep venous thrombosis (P > .999). CONCLUSION: Preoperative administration of tranexamic acid at a 1000 mg intravenous dose does not decrease transfusion rates or estimated blood loss in patients undergoing major oncologic surgery.

Central retinal vein occlusion associated with the use of tranexamic acid.

Here we report a case of central retinal vein occlusion that developed after using tranexamic acid. A 46-year-old female not known to have any previous illness came to the ophthalmology clinic complaining of sudden blurring of the vision in her left eye for almost 1 month, for which it is advised that tranexamic acid should be discontinued.

Bronchoscopic delivery of aminocaproic acid as a treatment for pulmonary bleeding: A case series.

OBJECTIVE: Bronchoscopy is an essential therapeutic modality in the treatment of pulmonary bleeding. Although numerous endoscopic treatments exist, topical ε-aminocaproic acid has not been described in the literature. This study documents the use of this novel treatment for pulmonary bleeding and compares it to available evidence for tranexamic acid, a similar anti-fibrinolytic agent. DESIGN: Case-series study. SETTING: ICU and general inpatient floors of a tertiary medical center. PATIENTS: Forty-six patients receiving endobronchial ε-aminocaproic acid for the treatment or prevention of pulmonary bleeding. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the study, 41.6% and 13% presented with non-massive and massive hemoptysis, respectively. In patients with active pulmonary bleeding, endobronchial application of ε-aminocaproic acid and accompanying therapies resulted in cessation of bleeding in 94.7% of cases. A total of six patients received ε-aminocaproic acid monotherapy; in three patients with active bleeding, 100% achieved hemostasis after treatment. Of the 36 patients successfully treated for active pulmonary bleeding, 27.8% had recurrent bleeding within 30 days. Thirty-day adverse events were as follows: death (10 patients), deep vein thrombosis (2 patients), renal failure (2 patients), and stroke (2 patients). CONCLUSIONS: Endobronchial administration of ε-aminocaproic acid during bronchoscopy may be a safe and efficacious option in the treatment and prevention of pulmonary bleeding. Further studies are necessary to better define ε-aminocaproic acid's safety profile, optimal routes of administration, and comparative effectiveness to tranexamic acid.

The TREATT Trial (TRial to EvaluAte Tranexamic acid therapy in Thrombocytopenia): safety and efficacy of tranexamic acid in patients with haematological malignancies with severe thrombocytopenia: study protocol for a double-blind randomised controlled trial.

BACKGROUND: Patients with haematological malignancies often develop thrombocytopenia as a consequence of either their disease or its treatment. Platelet transfusions are commonly given to raise a low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). Recent studies have shown that many patients continue to experience bleeding despite the use of prophylactic platelet transfusions. Tranexamic acid is an anti-fibrinolytic, which reduces the breakdown of clots formed in response to bleeding. Anti-fibrinolytics have been shown to prevent bleeding, decrease blood loss and use of red cell transfusions in elective and emergency surgery, and are used widely in these settings. The aim of this trial is to test whether giving tranexamic acid to patients receiving treatment for haematological malignancies reduces the risk of bleeding or death and the need for platelet transfusions. METHODS: This is a multinational randomised, double-blind, placebo-controlled, parallel, superiority trial. Patients will be randomly assigned to receive tranexamic acid (given intravenously or orally) or a matching placebo in a 1:1 ratio, stratified by site. Patients with haematological malignancies receiving intensive chemotherapy or stem cell transplantation (or both) who are at least 18 years of age and expected to become severely thrombocytopenic for at least 5 days will be eligible for this trial. The primary outcome of the trial is the proportion of patients who died or had bleeding of World Health Organization grade 2 or above during the first 30 days of the trial. We will measure the rates of bleeding daily by using a short, structured assessment of bleeding, and we will record the number of transfusions given to patients. We will assess the risk of arterial and venous thrombosis for 120 days from the start of trial treatment. DISCUSSION: This trial will assess the safety and efficacy of using prophylactic tranexamic acid during a period of intensive chemotherapy and associated thrombocytopenia in people with haematological disorders. TRIAL REGISTRATION: This study was prospectively registered on Current Controlled Trials on 25 March 2015 (ISRCTN73545489) and is also registered on ClinicalTrials.gov (NCT03136445).

Tranexamic acid for post-partum haemorrhage: What, who and when.

Tranexamic acid reduces bleeding by inhibiting the breakdown of blood clots. It is cost-effective and heat-stable with a long shelf life. In the WOMAN trial, tranexamic acid reduced deaths due to bleeding with no increase in thromboembolic events. The effect was greatest when women received tranexamic acid within 3 h of childbirth (RR = 0.69, 95% CI 0.52-0.91). The WHO recommends that women with post-partum haemorrhage receive 1 g tranexamic acid intravenously as soon as possible after giving birth, followed by a second dose if bleeding continues after 30 min or restarts within 24 h since the first dose. Urgent treatment is critical because women with post-partum haemorrhage bleed to death quickly, and tranexamic acid is most effective when given early. Evidence suggests there is no benefit when the drug is given more than 3 h after bleeding onset. Alternative routes of administration and use of tranexamic acid in the prevention of post-partum haemorrhage are research priorities.

A copper(II) paddle-wheel structure of tranexamic acid: di-chloro-tetra-kis-[µ-4-(ammonio-meth-yl)cyclo-hexane-1-carboxyl-ato-O,O']dicopper(II) dichloride hexa-hydrate.

Tranexamic acid [systematic name: trans-4-(amino-meth-yl)cyclo-hexane-1-carb-oxy-lic acid], is an anti-fibrinolytic amino acid that exists as a zwitterion [trans-4-(ammonio-meth-yl)cyclo-hexane-1-carboxyl-ate] in the solid state. Its reaction with copper chloride leads to the formation of a compound with a copper(II) paddle-wheel structure that crystallizes as a hexa-hydrate, [Cu2Cl2(C8H15NO2)4]2+·2Cl-·6H2O. The asymmetric unit is composed of a copper(II) cation, two zwitterionic tranexamic acid units, a coordinating Cl- anion and a free Cl- anion, together with three water mol-ecules of crystallization. The whole structure is generated by inversion symmetry, with the Cu⋯Cu axle of the paddle-wheel dication being located about a center of symmetry. The cyclo-hexane rings of the zwitterionic tranexamic acid units have chair conformations. The carboxyl-ate groups that bridge the two copper(II) cations are inclined to one another by 88.4 (8)°. The copper(II) cation is ligated by four carboxyl-ate O atoms in the equatorial plane and by a Cl- ion in the axial position. Hence, it has a fivefold O4Cl coordination sphere with a perfect square-pyramidal geometry and a τ5 index of zero. In the crystal, the paddle-wheel dications are linked by a series of N-H⋯Cl hydrogen bonds, involving the coordinating and free Cl- ions, forming a three-dimensional network. This network is strengthened by a series of N-H⋯Owater, Owater-H⋯Cl and Owater-H⋯O hydrogen bonds.

Anti-fibrinolytic and anti-microbial activities of a serine protease inhibitor from honeybee (Apis cerana) venom.

Bee venom contains a variety of peptide constituents, including low-molecular-weight protease inhibitors. While the putative low-molecular-weight serine protease inhibitor Api m 6 containing a trypsin inhibitor-like cysteine-rich domain was identified from honeybee (Apis mellifera) venom, no anti-fibrinolytic or anti-microbial roles for this inhibitor have been elucidated. In this study, we identified an Asiatic honeybee (A. cerana) venom serine protease inhibitor (AcVSPI) that was shown to act as a microbial serine protease inhibitor and plasmin inhibitor. AcVSPI was found to consist of a trypsin inhibitor-like domain that displays ten cysteine residues. Interestingly, the AcVSPI peptide sequence exhibited high similarity to the putative low-molecular-weight serine protease inhibitor Api m 6, which suggests that AcVSPI is an allergen Api m 6-like peptide. Recombinant AcVSPI was expressed in baculovirus-infected insect cells, and it demonstrated inhibitory activity against trypsin, but not chymotrypsin. Additionally, AcVSPI has inhibitory effects against plasmin and microbial serine proteases; however, it does not have any detectable inhibitory effects on thrombin or elastase. Consistent with these inhibitory effects, AcVSPI inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products. AcVSPI also bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi as well as gram-positive and gram-negative bacteria. These findings demonstrate the anti-fibrinolytic and anti-microbial roles of AcVSPI as a serine protease inhibitor.