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The public enquiry into the mass casualty incident at the Manchester Arena in the UK in which 23 people died and over 1000 were injured, identified the need for timely intramuscular administration of tranexamic acid to trauma patients. Since then, a number of studies and trials have been carried out and UK paramedics are now authorized to give intramuscular tranexamic acid in the pre-hospital setting. In Japan, pre-hospital administration by emergency life-saving technicians is not yet authorized, despite the fact that tranexamic acid was invented by Japanese scientists. In Japan, the need for the pre-hospital administration of tranexamic acid has been raised on several occasions, where a patient died from traumatic bleeding prior to hospital admission. This paper summarizes the evidence on the use of tranexamic acid in patients with traumatic bleeding, including new evidence on the intramuscular route. [ABSTRACT FROM AUTHOR]

Background: Women are less likely than men to receive some emergency treatments. This study examines whether the effect of tranexamic acid (TXA) on mortality in trauma patients varies by sex and whether the receipt of TXA by trauma patients varies by sex.Methods: First, we conducted a sex-disaggregated analysis of data from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH)-2 and CRASH-3 trials. We used interaction tests to determine whether the treatment effect varied by sex. Second, we examined data from the Trauma and Audit Research Network (TARN) to explore sex differences in the receipt of TXA. We used logistic regression models to estimate the odds ratio for receipt of TXA in females compared with males. Results are reported as n (%), risk ratios (RR), and odds ratios (OR) with 95% confidence intervals.Results: Overall, 20 211 polytrauma patients (CRASH-2) and 12 737 patients with traumatic brain injuries (CRASH-3) were included in our analysis. TXA reduced the risk of death in females (RR=0.69 [0.52-0.91]) and in males (RR=0.80 [0.71-0.90]) with no significant heterogeneity by sex (P=0.34). We examined TARN data for 216 364 patients aged ≥16 yr with an Injury Severity Score ≥9 with 98 879 (46%) females and 117 485 (54%) males. TXA was received by 7198 (7.3% [7.1-7.4%]) of the females and 19 697 (16.8% [16.6-17.0%]) of the males (OR=0.39 [0.38-0.40]). The sex difference in the receipt of TXA increased with increasing age.Conclusions: Administration of TXA to patients with bleeding trauma reduces mortality to a similar extent in women and men, but women are substantially less likely to be treated with TXA. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid reduces head injury deaths in patients with CT scan evidence of intracranial bleeding after mild traumatic brain injury (TBI). However, the cost-effectiveness of tranexamic acid for people with mild TBI in the pre-hospital setting, prior to CT scanning, is uncertain. A large randomised controlled trial (CRASH-4) is planned to address this issue, but the economic justification for it has not been established. The aim of the analysis was to estimate the likelihood of tranexamic acid being cost-effective given current evidence, the treatment effects required for cost-effectiveness, and the expected value of performing further research.Methods: An early economic decision model compared usual care for mild TBI with and without tranexamic acid, for adults aged 70 and above. The evaluation was performed from a UK healthcare perspective over a lifetime time horizon, with costs reported in 2020 pounds (GBP) and outcomes reported as quality-adjusted life years (QALYs). All analyses used a £20,000 per QALY cost-effectiveness threshold.Results: In the base case analysis, tranexamic acid was associated with an incremental cost-effectiveness ratio of £4885 per QALY gained, but the likelihood of it being cost-effective was highly dependent on the all-cause mortality treatment effect. The value of perfect information was £22.4 million, and the value of perfect information for parameters that could be collected in a trial was £21.9 million. The all-cause mortality risk ratio for tranexamic acid and the functional outcomes following TBI had the most impact on cost-effectiveness.Conclusions: There is a high degree of uncertainty in the cost-effectiveness of tranexamic acid for older adults experiencing mild TBI, meaning there is a high value of performing future research in the UK. The value in a global context is likely to be far higher. [ABSTRACT FROM AUTHOR]

This study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data were collected retrospectively from patient electronic records and hospital transfusion databases recording issue of blood products from January 2016 to December 2018. Of 134 patients with MH, 24 had activated MHP and 110 did not have activated MHP. Groups were similar for age, sex, baseline hemoglobin, platelet count, coagulation screen, and renal function with no difference in the baseline clinical characteristics. The total number of red cell units (median and [IQR]) transfused was no different in the patients with activated (7.5 [5–11.75]) versus nonactivated (9 [6–12]) MHP ( p  = 0.35). Patients in the nonactivated MHP group received significantly higher number of platelet units (median: 3 vs. 2, p  = 0.014), plasma (median: 4.5 vs. 1.5, p  = 0.0007), and cryoprecipitate (median: 2 vs. 1, p  = 0.008). However, activation of MHP was associated with higher mortality at 24 hours compared with patients with nonactivation of MHP (33.3 vs. 10.9%, p  = 0.005) and 30 days (58.3 vs. 30.9%, p  = 0.01). The total RBC and platelet (but not fresh frozen plasma [FFP]) units received were higher in deceased patients than in survivors. Increased mortality was associated with a higher RBC:FFP ratio. Only 26% of patients received tranexamic acid and these patients had higher mortality at 30 days but not at 24 hours. Deceased patients at 30 days had higher levels of fibrinogen than those who survived (median: 2.4 vs. 1.8, p  = 0.01). Patients with activated MHP had significantly higher mortality at both 24 hours and 30 days despite lack of difference in the baseline characteristics of the patients with activated MHP versus nonactivated MHP groups. The increased mortality associated with a higher RBC:FFP ratio suggests dilutional coagulopathy may contribute to mortality, but higher fibrinogen at baseline was not protective. [ABSTRACT FROM AUTHOR]

Background: Intravenous tranexamic acid (TXA) reduces bleeding deaths after injury and childbirth. It is most effective when given early. In many countries, pre-hospital care is provided by people who cannot give i.v. injections. We examined the pharmacokinetics of intramuscular TXA in bleeding trauma patients.Methods: We conducted an open-label pharmacokinetic study in two UK hospitals. Thirty bleeding trauma patients received a loading dose of TXA 1 g i.v., as per guidelines. The second TXA dose was given as two 5 ml (0·5 g each) i.m. injections. We collected blood at intervals and monitored injection sites. We measured TXA concentrations using liquid chromatography coupled to mass spectrometry. We assessed the concentration time course using non-linear mixed-effect models with age, sex, ethnicity, body weight, type of injury, signs of shock, and glomerular filtration rate as possible covariates.Results: Intramuscular TXA was well tolerated with only mild injection site reactions. A two-compartment open model with first-order absorption and elimination best described the data. For a 70-kg patient, aged 44 yr without signs of shock, the population estimates were 1.94 h-1 for i.m. absorption constant, 0.77 for i.m. bioavailability, 7.1 L h-1 for elimination clearance, 11.7 L h-1 for inter-compartmental clearance, 16.1 L volume of central compartment, and 9.4 L volume of the peripheral compartment. The time to reach therapeutic concentrations (5 or 10 mg L-1) after a single intramuscular TXA 1 g injection are 4 or 11 min, with the time above these concentrations being 10 or 5.6 h, respectively.Conclusions: In bleeding trauma patients, intramuscular TXA is well tolerated and rapidly absorbed.Clinical Trial Registration: 2019-000898-23 (EudraCT); NCT03875937 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

In the UK, tranexamic acid is recommended for all surgical procedures where expected blood loss exceeds 500 ml. However, the optimal dose, route and timing of administration are not known. This study aimed to evaluate current practice of peri-operative tranexamic acid administration. Patients undergoing primary total hip arthroplasty, total knee arthroplasty or unicompartmental knee arthroplasty during a 2-week period were eligible for inclusion in this prospective study. The primary outcome was the proportion of patients receiving tranexamic acid in the peri-operative period. Secondary outcomes included: dose, route and timing of tranexamic acid administration; prevalence of pre- and postoperative anaemia; estimated blood loss; and red blood cell transfusion rates. In total, we recruited 1701 patients from 56 NHS hospitals. Out of these, 1523 (89.5%) patients received tranexamic acid and of those, 1052 (69.1%) received a single dose of 1000 mg intravenously either pre- or intra-operatively. Out of the 1701 patients, 571 (33.6%) and 1386 (81.5%) patients were anaemic (haemoglobin < 130 g.l-1 ) in the pre- and postoperative period, respectively. Mean (SD) estimated blood loss for all included patients was 792 (453) ml and 54 patients (3.1%) received a red blood cell transfusion postoperatively. The transfusion rate for patients with pre-operative anaemia was 6.5%, compared with 1.5% in patients without anaemia. Current standard of care in the UK is to administer 1000 mg of tranexamic intravenously either pre- or intra-operatively. Approximately one-third of patients present for surgery with anaemia, although the overall red blood cell transfusion rate is low. These data provide useful comparators when assessing the efficacy of tranexamic acid and other patient blood management interventions in future studies. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82-1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.Funding: UK National Institute for Health Research Health Technology Assessment Programme. [ABSTRACT FROM AUTHOR]

Preoperative anaemia is common, seen in a third of patients before major surgery. Both preoperative anaemia and blood transfusion are associated with increased patient risk and adverse outcome. Patient Blood Management (PBM) is the multidisciplinary, multimodal approach to optimising the care of patients who may require blood transfusion. Guidelines exist with many recommendations throughout the perioperative pathway. However, the efficacy of individual recommendations as an intervention in terms of clinical outcome can be confusing. In the UK the first national audit of PBM in surgery was carried out in 2015. This reviewed the use and impact of PBM recommendations in hospitals throughout the UK where major surgery was undertaken. The current evidence base for these PBM recommendations was reviewed and the patient outcome in terms of blood transfusion use and length of hospital stay assessed in those where PBM interventions were followed. For the patient who presents with preoperative anaemia, 'quick wins' were identified that reduced blood transfusion use and reduced length of stay in hospital; preoperative discontinuation of anticoagulation or antiplatelet therapy, and intraoperative use of tranexamic acid and cell salvage. [ABSTRACT FROM AUTHOR]

The article offers information on Patient blood management in NHS Blood and Transplant (NHSBT). It mentions Blood Stocks Management Scheme is a Great Britain-wide function supporting blood inventory management across the blood supply chain and provides benchmarking data and advice to hospitals on best practice in stock management.

Background: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care., Objective: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients., Methods: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data., Results: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home., Conclusions: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Keywords: -2 antiplasmin deficiency; thrombogenomics; bleeding disorder Congenital deficiency of SB 2 sb -AP is extremely rare, with fewer than 18 cases reported worldwide (Pozzi I et al i , [6]) and causes a significant bleeding disorder due to uninhibited hyperfibrinolysis. We report a family with a novel germline variant in I SERPINF2 i causing SB 2 sb -AP deficiency and discuss some of the challenges faced in the management of this rare bleeding disorder. Given the bleeding phenotype of the index patient, our view is that current available therapy is insufficient to mitigate the potential bleeding risk associated with this orthopaedic intervention. [Extracted from the article]

Urticaria is characterized by the sudden development of wheals and/or angioedema. It is a common problem. Acute spontaneous urticaria is the most common form of urticaria, affecting up to 1 in 7 British children. About one-third will progress to chronic or recurrent urticaria. This article highlights the value of a good history and reviews the treatment options available for children. The diagnosis is usually made on clinical grounds, by a thorough history of eliciting factors. Further investigations should be guided by the urticaria subtype and are often unnecessary. Acute spontaneous urticaria is usually secondary to a viral infection ± antibiotic use. Viral infections are usually responsible for flare-ups. In older children, chronic spontaneous urticaria may by associated with antibodies to the α chain of the high-affinity IgE receptor or, less commonly, other autoimmune disease. Dermographism and cold urticaria are the commonest forms of inducible urticaria in childhood. Symptomatic relief is usually achieved by elimination of triggers and the use of non-sedating antihistamines. Tranexamic acid is useful to control isolated angioedema. Unresponsive cases may improve with the addition of a leukotriene receptor antagonist, anti IgE therapy or systemic immunosuppression (e.g. Ciclosporin A). Short courses of oral steroids are helpful to control acute episodes and severe exacerbations of chronic spontaneous urticaria. Urticaria remits over time. After 3 years, a quarter of children with chronic spontaneous urticaria are disease free and the vast majority are disease free after 7 years. [ABSTRACT FROM AUTHOR]

The article discusses the guidelines issued by the British National Institute for Health and Care Excellence (NICE) on the assessment and initial management of major trauma. Topics covered include the need for an effective assessment of trauma patients in identifying life threatening injuries, the imaging for patients with suspected major haemorrhage and chest trauma and the management of haemorrhage in the hospital setting.

Following results of large randomised control trials such as the CRASH-2 trial and MATTERs, tranexamic acid has now been included in the UK paramedics armamentarium for haemorrhagic trauma. The objective of this literature review is to use evidence yielded through a selection of search databases to explore the use of tranexamic acid for non-compressible haemorrhage, while relating such literature to UK paramedic practice. In doing so, this article highlights the benefit in using tranexamic acid for non-compressible haemorrhage and discusses potential recommendations for future paramedic practice. [ABSTRACT FROM AUTHOR]

The article talks about major trauma which causes a significant number of death worldwide and a large proportion of the deaths being due to haemorrhage. Topics discussed include how to manage haemorrhage in major trauma, why major haemorrhage can cause problems, and the complications that can arise when conducting a blood transfusion post trauma.

Background: Bleeding of unknown cause (BUC) and unclassified bleeding disorders (UBD) are increasingly recognized. There is no guidance on diagnosis and management., Objectives: To examine UK haemophilia centre registration patterns and current practice for UBD patients., Methods: In a two-step process, the UK National Haemophilia Database (NHD) was reviewed for registration patterns of UBD patients and a survey of UK haemophilia centers was conducted (January/February 2021) to capture current practice for diagnosis and management of patients with UBD., Results/discussion: Overall, registrations with the NHD for UBD patients has sharply risen from 2012 to 2020 and in 2019 accounted for 2.65% of registered patients. For the survey, the response rate was 52/67 (78%). Practice was widely variable; 35/52 (67%) centers register UBD; among these 35 centers, terminology included UBD (28 centers), undiagnosed bleeding disorder (four centers), and BUC (three centers); 34/52 (65%) centers use a formal bleeding assessment tool. For management of dental extraction and high bleeding risk surgery in a fictional UBD patient we found that tranexamic acid was widely used; however, beyond this a variety of hemostatic products were advised including blood products, recombinant factor VIIa/prothrombin complex concentrate, and desmopressin. There was general consensus (≈90%) on avoiding regional anesthesia in pregnancy, but no agreement on the need for fetal precautions to avoid bleeding at delivery (50% would advise these). There was a disparity of opinion on chemical thromboprophylaxis, and management of patients without prior hemostatic challenges and offspring of these patients., Conclusion: This study provides a snapshot of current practice and real-world data in this area. Future studies need to address the gaps in evidence., (© 2021 International Society on Thrombosis and Haemostasis.)

Objective: High-dose tranexamic acid (TXA) can cause seizures in patients who have undergone pulmonary endarterectomy (PTE). Seizures secondary to TXA will resolve once the drug is excreted from the body, and the patients do not have to be on long-term anticonvulsants. The aim of the study is to find out if medication review in the hospital has led to deprescribing of anticonvulsants for TXA-associated seizures on discharge from the critical care unit (CCU) and hospital., Methods: This is a single-centre retrospective study conducted at a tertiary cardiothoracic hospital between 2012 and 2017. The inclusion criteria consisted of all adult patients who have undergone PTE surgery. Patients who were started on anticonvulsants preoperatively or postoperatively for seizures secondary to organic causes were excluded., Results: A total of 933 patients underwent PTE from January 2012 to August 2017. 25 patients had TXA-related seizures postoperatively and were started on anticonvulsant therapy, giving an incidence of 2.7%. 15 patients were discharged from the CCU without anticonvulsants. A further three patients had their anticonvulsants deprescribed in the ward before being discharged from the hospital., Conclusion: Deprescribing of anticonvulsants after benign seizures secondary to high-dose TXA is facilitated by verbal and written handover, which can be improved in our hospital. A detailed handover summary, as well as a discharge letter with clearly defined instructions for drug review, is needed to make deprescribing a more robust process., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

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).

Current attitudes to the medical management of traumatic hyphaema were investigated by means of a postal survey. A single page questionnaire was sent to all consultant ophthalmologists in the UK who were members of the college of ophthalmologists. The response rate was 50%. Opinion was sharply divided on the use of bed rest, padding and topical therapy. However, there was almost universal agreement that systemic therapy, either steroids or antifibrinolytics, were not indicated. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted by Jashvant Poeran and colleagues which aims to assess the perioperative use of the medication tranexamic acid in total hip and total knee arthroplasties without the need for blood transfusions and risks for thromboembolic and renal problems. Topics discussed include the summary answer and the main result of the study, what the research adds on previous studies on tranexamic acid use, and the methodology of the study.