Tranexamic acid (TXA), approved initially for medical bleeding, has expanded its utility to various surgical contexts, including pediatric orthopedic and trauma surgery, though limited research has been conducted in this population. This study aimed to evaluate TXA's efficacy and safety in pediatric orthopedic and trauma surgeries, focusing on its impact on blood loss reduction and transfusion requirements. Through a comprehensive literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, eight retrospective studies were analyzed, all involving pediatric patients with cerebral palsy undergoing orthopedic surgery. TXA dosing regimens varied across studies, with loading doses ranging from 10 to 50 mg/kg and maintenance doses from 1 to 10 mg/kg/h. Consistently, TXA administration was associated with a significant decrease in intraoperative blood loss and transfusion needs compared with nonadministered groups, with no reported thromboembolic events, indicating its safety in pediatric orthopedic and trauma surgeries.

Treatment for neuromuscular hip dysplasia (NMHD) typically involves osteotomies of the proximal femur and/or pelvis, and the potential for significant volume blood loss is high. Tranexamic acid (TXA) functions as an antifibinolytic and has been shown to reduce bleeding in many operative settings. Retrospective evidence for the use of TXA in children undergoing NMHD reconstruction is inconclusive, and to our knowledge, prospective evaluation has never been performed. The purpose of this study was to examine the effectiveness of TXA use on intra- and postoperative outcomes during bony reconstruction for NMHD. In this matched comparative study, a prospective cohort of patients undergoing bony reconstruction for NMHD who were given TXA was enrolled and then matched to a retrospective cohort who previously underwent the same surgery without administration of TXA. The primary outcome variable was a change in perioperative hemoglobin values from preoperative to 1 day postoperatively. Secondary objectives were percent loss of estimated blood volume, postoperative transfusion requirements, and length of hospital stay. Forty-eight patients, 24 in each cohort, were included in the analyses. Mean age at surgery was 7.09 years (±2.5). Fifty percent of each cohort underwent bilateral varus derotational osteotomy with pelvic acetabuloplasty. No statistical differences were found in postoperative hemoglobin differences ( P  = 0.18), length of hospital stay ( P  = 0.45), or blood transfusion requirements ( P  = 0.56) between cohorts. Intraoperative administration of TXA to patients undergoing bony reconstruction for NMHD was not found to reduce postoperative blood loss or requirement for blood transfusion. Future studies should employ a larger, prospective randomized controlled trial to verify these findings.

Hemostatic impairment may exacerbate postpartum hemorrhage (PPH). Previously, we described a distinct coagulopathy, associated with multiple causes of PPH including placental abruption and amniotic fluid embolus, termed acute obstetric coagulopathy (AOC). AOC is characterized by very high plasmin/antiplasmin complexes and rapid depletion of functional fibrinogen and factor V (FV). To determine mechanisms underlying AOC, we investigated the plasma from 12 women with AOC (defined by raised plasmin/antiplasmin) and 21 with severe PPH (blood loss >2000 mL or placental abruption) without AOC. Plasma from patients with AOC had a fourfold increased ability to generate plasmin compared with those with severe PPH without AOC (P < .0002). AOC was associated with fibrinogen cleavage in the circulation, demonstrated by fragment D and other breakdown products (P < .0001). D-dimer was increased 36-fold in AOC compared with severe PPH without AOC, thrombin/antithrombin complexes were not raised. FV was reduced on western blot in AOC but not severe PPH without AOC (P < .001) suggesting FV cleavage. Confocal microscopy revealed similar clot structure between AOC and non-AOC samples, but both groups differed from nonbleeding pregnant controls. These data suggest that in AOC an excess of plasmin cleaves fibrinogen and FV in the circulation causing a specific, pathognomonic depletion of coagulation factors. Fibrin(ogen) breakdown products have cofactor function for tissue plasminogen activator, and these data are consistent with these breakdown products, enhancing plasmin generation and potentially driving aberrant plasmin generation in AOC. These results have implications for the clinical management of coagulopathy during PPH.

This chapter provides insight into current management strategies for the placenta accreta spectrum (PAS). PAS is one of the most morbid conditions of pregnancy, with significant maternal hemorrhage and surgical morbidity risks, and its increasing incidence. Here, we review the available data to help guide the clinical management of PAS, from time of diagnosis through delivery and postpartum care, while acknowledging the many areas of continued uncertainty. The evidence is strong for the importance of team-based, patient-centered, and multidisciplinary care for patients with PAS. However, much else remains uncertain and is predominantly guided by expert opinion. Ultimately, we aim to provide a current understanding of available literature and to emphasize that continued research is paramount to explore management and surgical approaches to move toward optimization of patient outcomes, including the patient experience.

Placenta accreta spectrum (PAS) disorder, characterized by failure of the abnormally adherent placenta to detach from the uterus after delivery, is a leading cause of severe maternal morbidity. Despite its relatively low incidence, disproportional contributions to perinatal hemorrhage, massive transfusion, and emergency hysterectomy underscore the critical need for development of evidence-based surgical management strategies for PAS. There is clear benefit to preoperative management of anemia, as well as preparation for intraoperative resuscitation with blood products and cell salvage. Several tenets of normal cesarean delivery should be maintained in PAS delivery such as the use of neuraxial anesthesia until delivery, prophylactic antibiotics, mechanical thromboprophylaxis intraoperatively, and administration of tranexamic acid if excessive bleeding occurs. Elements of surgical management distinctive to PAS and accepted as best practice include the following: planning delivery at centers with experienced teams when PAS is suspected antenatally, global intraoperative uterine and pelvic survey on entry into the abdominal cavity to assess for anatomic distortion or abnormal vascularity, selection of hysterotomy site for delivery well away from the placental margin, and direct visual assessment of the placental relationship with the myometrium after neonatal delivery and during the start of uterine involution. Other morbidity-reducing strategies such as routine cystoscopy with or without ureteral stent placement, unconventional transverse abdominal entry, hysterotomy extension with surgical staplers, and endovascular hemorrhage reduction tactics involving aortic or iliac balloon occlusion and multivessel arterial embolization remain experimental and require further research.

Direct oral anticoagulants (DOACs) are widely prescribed to prevent and treat venous and arterial thromboembolism, supported by published evidence, and are preferred over warfarin in many guidelines. Although the risk of major bleeding, in particular intracranial haemorrhage (ICH), is decreased with DOACs, gastrointestinal bleeding is increased with some DOACs, and the case fatality rate of bleeding remains high. Therefore, it is important to (i) prescribe DOACs appropriately, (ii) have strategies to manage major bleeding including the use of specific reversal agents and (iii) interrupt and resume DOACs for procedures. The main recommendations are as follows: (i) Select the appropriate dose of DOAC according to indications and consider patient factors to minimise bleeding risks; (ii) DOACs do not require routine laboratory testing; (iii) for life-threatening uncontrollable bleeding, specific agents can be used to reverse the anticoagulant effects of DOACs; and (iv) DOACs can be interrupted for planned procedures without the need for 'bridging' with low-molecular-weight heparin (LMWH). The anticoagulant effects of DOACs can be reversed with specific agents, such as andexanet for apixaban and rivaroxaban and idarucizumab for dabigatran. If not available, pro-haemostatic agents such as prothrombin complex concentrates or activated prothrombin complex concentrates can be considered. DOACs can be interrupted and resumed for procedures without the need for 'bridging' with LMWH.

Evaluate the use of tranexamic acid (TXA) and observation as a management option for pediatric patients presenting with posttonsillectomy hemorrhage (PTH).

Retrospective analysis of a prospectively implemented quality improvement initiative with a historical control comparison group.

Tertiary children's hospital.

Patients <18 years of age who underwent adenotonsillectomy (AT) and returned to the Emergency Department for PTH were included. Patients who were stable without large volume or active bleeding were given intravenous TXA and admitted for overnight observation. Data were compared in a before-and-after analysis: preprotocol (April 2022 to March 2023) versus postprotocol (April 2023 to March 2024). For cost-effectiveness analysis, we analyzed aggregated claims data from a commercial claims database.

Preprotocol 1800 adenotonsillectomies were performed, and 40 procedures were performed for control of hemorrhage (2.2 per 100 AT). Postprotocol 2356 adenotonsillectomies were performed, and 30 procedures were performed to control hemorrhage (1.3 per 100 AT) showing a significant reduction in return to the operating room (relative risk [RR] = 0.59, 95% confidence interval [CI] [0.358, 0.916], P-value .020). There were no reported adverse events attributable to TXA. An estimated 21 surgeries were avoided, and 26 additional patients were observed in the hospital during the postprotocol period, for an estimated net cost savings of $174,970.

The implementation of a standardized TXA protocol significantly reduced the need for return to the operating room for PTH in pediatric patients, without complications and with net cost savings to the health care system.

Acute hemorrhage can be a life-threatening emergency that is complex in its management and affects many patient populations. The past 15 years has seen the introduction of comprehensive massive hemorrhage protocols, wider use of viscoelastic testing, new coagulation factor products, and the publication of robust randomized controlled trials in diverse bleeding patient populations. Although gaps continue to exist in the evidence base for several aspects of patient care, there is now sufficient evidence to allow for an individualized hemostatic response based on the type of bleeding and specific hemostatic defects. We present 3 clinical cases that highlight some of the challenges in acute hemorrhage management, focusing on the importance of interprofessional communication, rapid provision of hemostatic resuscitation, repeated measures of coagulation, immediate administration of tranexamic acid, and prioritization of surgical or radiologic control of hemorrhage. This article provides a framework for the clear and collaborative conversation between the bedside clinical team and the consulting hematologist to achieve prompt and targeted hemostatic resuscitation. In addition to providing consultations on the hemostatic management of individual patients, the hematology service must be involved in setting hospital policies for the prevention and management of patients with major hemorrhage.

We carried out a study to assess the efficacy of tranexamic acid in preventing scar tissue in the craniectomy area in rats.

Our study consisted of control and tranexamic acid groups with 10 subjects each. All subjects underwent bilateral frontoparietal craniectomy. After craniectomy, cotton pads were applied to the surgical sites. In the controls, the pads were soaked with saline and in the tranexamic acid group the pads were soaked with 30 mg/kg tranexamic acid. Rats were decapitated 30 days after surgery. The degree of scar formation was evaluated pathologically and by electron microscopy. In pathologic evaluation, dura mater thickness, scar tissue density, and arachnoid involvement were evaluated.

The outcomes demonstrated that no adhesions were present in the rats of the Tranexamic acid group, whereas the control group exhibited severe scar tissue [eight of ten rats (80%)] with adhesions. Additionally, comparison between the two groups showed that the dura mater thickness of tranexamic acid animals was thinner than that of the control group animals. Similarly, the intensity of scar tissue density and the intensity of arachnoid involvement were much better than the control group.

Scar tissue formation following craniectomies represents a significant adverse outcome that may lead to various complications. Intraoperative topical application of tranexamic acid has demonstrated potential efficacy in preventing scar formation in the craniectomy region in rat models.

Disseminated intravascular coagulation (DIC) is a complex condition with diverse etiologies. While its association with sepsis has been widely studied, less focus has been given to DIC arising from other critical conditions, such as trauma, burns, acute pancreatitis, and obstetric complications. The 2024 Clinical Practice Guidelines, developed by the Japanese Society on Thrombosis and Hemostasis (JSTH), aim to fill this gap and offer comprehensive recommendations for managing DIC across various conditions. This study, Part 4 of the guideline series, addresses DIC management in trauma, burns, obstetric complications, acute pancreatitis/liver failure, viral infections, and autoimmune diseases. For trauma-associated DIC, early administration of fresh-frozen plasma (FFP), coagulation factor concentrates such as fibrinogen and prothrombin complex concentrates, and tranexamic acid is recommended. The guidelines also highlight DIC in obstetrics, which is associated with massive bleeding, and recommend the administration of fibrinogen concentrate, antithrombin concentrate, and tranexamic acid. Through a systematic review of the current evidence, the guidelines provide stratified recommendations aimed at improving clinical outcomes in DIC management beyond sepsis, thereby serving as a valuable resource for healthcare providers globally.

Tranexamic acid (TXA) is an antifibrinolytic agent that is successfully used in many medical fields to reduce blood loss. In plastic surgery, the systemic administration of TXA has been associated with less hematoma and seroma formation, and consequently, a reduction in the length of hospital stay (LOS). The aim of this study was to evaluate if the topical administration of TXA in patients undergoing abdominoplasty leads to a decrease in the daily drainage volume; earlier drain removal; and possibly, a shorter LOS.

In this single-center, comparative study, 60 patients undergoing abdominoplasty received either topical TXA treatment (n = 30; 1 g) or no treatment (n = 30). The primary endpoints were daily drainage volume, time until drain removal, and total LOS. Variables such as sex, age, body mass index, weight of resected skin and underlying fat, and concomitant liposuction were considered in the statistical analysis as covariates.

In the TXA group, 54% less total drainage volume was observed (P < 0.01). The time until drain removal and LOS were reduced by 23% (P < 0.01) and 24% (P < 0.01), respectively, compared with the control group. Moreover, it was found that daily drainage volume increased with age.

Topical TXA administration reduces daily drainage volume, time until drain removal, and LOS significantly in patients undergoing abdominoplasty. Further studies analyzing the superiority of topical TXA compared with systemic TXA, as well as studies investigating the ideal TXA dosage could deliver further valuable information.

Tranexamic acid is an antifibrinolytic agent routinely used during hip and knee joint replacement surgery to minimize bleeding. Chronic kidney disease is a common chronic health problem seen among adults requiring major arthroplasty surgery. Tranexamic acid is renally cleared and may accumulate in chronic kidney disease. Optimal tranexamic acid dosing and dose adjustment for chronic kidney disease patients needing major arthroplasty is unknown. The objective of this study was to serially measure plasma tranexamic acid concentrations in patients with varied kidney function undergoing hip or knee replacement surgery for population pharmacokinetic modeling and to guide new dosing recommendations.

A prospective cohort study enrolled 21 adults undergoing hip or knee replacement surgery between June 2020 and September 2022. Based on estimated glomerular filtration rate, the patients were stratified into good (greater than or equal to 60 ml · min -1 · 1.73 m -2 ) and poor (less than 60 ml · min -1 · 1.73 m -2 ) renal function. Serial blood samples were taken to measure plasma tranexamic acid concentration levels (primary outcome) after an intravenous tranexamic acid 20-mg/kg bolus dose after anesthesia induction. Secondary clinical outcomes included adverse events (thromboembolic events, seizures), red cell transfusion, mortality, and length of hospital stay. Analyses used curve stripping and population pharmacokinetic modeling and simulation.

Plasma tranexamic acid concentration levels were higher in patients with poor renal function and clearance compared to those with good renal function. Population pharmacokinetic modeling tested various tranexamic acid bolus and maintenance infusion regimens. Simulations revealed that single-bolus tranexamic acid administration leads to rapid rise and decline in plasma concentrations. This study identified that plasma tranexamic acid levels of 50 to 75 mg/l were maintained for approximately 4 h using a tranexamic acid bolus infusion of 15 mg/kg over a 15-min duration together with a maintenance infusion of 7.5 or 5 mg · kg -1 · h -1 for 2 h for the good and poor renal function groups, respectively. There was no difference in secondary outcomes.

Population pharmacokinetic modeling and simulation resulted in recommendations for a new dosing regimen to optimize the antifibrinolytic effect of tranexamic acid and avoid excessive dosing.

Traumatic brain injury (TBI) is a prevalent cause of morbidity and mortality worldwide. A focus on neuroprotective agents to prevent the secondary injury cascade that follows moderate-to-severe TBI has informed the field greatly but has not yielded any viable therapeutic options to date. New strategies and pharmacotherapy options for neuroprotection continue to be evaluated, including tranexamic acid, progesterone, cerebrolysin, cyclosporin A, citicholine, memantine, and lactate. Biomarkers of injury that can aid in diagnosis and prognosis have also been elucidated and are incrementally being used in clinical practice. The spectrum of TBI severity has also gained increasing attention as it relates to mild TBI or concussion, blast injury, and subacute or chronic subdural hematomas. In this review, we review the pathophysiology, recent clinical trials, and future directions for acute TBI.

Postpartum hemorrhage is the leading cause of maternal mortality worldwide. Several studies have confirmed that tranexamic acid is effective in treating postpartum hemorrhage once started, but its prophylactic effect is under debate. As of now, most studies involve intravenous administration, and the uptake of tranexamic acid in women during active labor is unknown. This is a pilot study in preparation for a larger randomized controlled trial on the prophylactic effect of oral tranexamic acid on postpartum hemorrhage. The study aims to assess the uptake of oral tranexamic acid during active labor.

Our study is a pilot intervention study. The study population consisted of 51 women ≥36 gestational weeks with planned vaginal delivery at Södersjukhuset, Stockholm, from December 2022 through February 2023. The participants were randomized 1:1:1:1 to receive 2 g of tranexamic acid as an oral solution, tablets, effervescent tablets, or 1 g of intravenous tranexamic acid, near full cervical dilatation. Blood samples were taken before and 30, 60, 120, 240, 360, and 480 min after tranexamic acid administration. Plasma concentration of tranexamic acid was measured using liquid chromatography-tandem mass spectrometry. Mean values were compared between groups using analysis of variance. Our main outcome measures were time to therapeutic level, duration in therapeutic interval, and maximum plasma concentration of tranexamic acid.

Therapeutic level (5.0 mg/L) was reached at the 2-h time point for oral (7.11 ± 3.31 mg/L) and the 30-min time point for intravenous forms (30.6 ± 15.0 mg/L). Duration in therapeutic intervals for oral and intravenous forms was 6 and 3.5 h (p < 0.007). Peak plasma concentrations for oral and intravenous forms were 10.2 ± 3.9 mg/L and 30.6 ± 15.0 mg/L, respectively (p < 0.001). Time-to-therapeutic level (p = 0.08), duration in therapeutic interval (p = 0.92), or peak concentration (p = 0.73) did not differ between oral forms. Overall, 37 women (88%) found the intake of oral tranexamic acid during active labor acceptable.

All oral forms of tranexamic acid show similar and adequate uptake when administered during labor. Uptake is lower and slower compared with intravenous administration, but the duration in the therapeutic interval is longer.

Perioperative management practices in liver transplantation (LT) evolve very quickly. There are few specific recommendations, often based on a low level of evidence, resulting in wide heterogeneity of practices.

We performed a survey in all 16 French centers in 2021 by focusing on center organization, preoperative cardiovascular assessment, antimicrobial prophylaxis, hemostasis management, intraoperative use of hemodynamic monitoring and renal replacement therapy, immunosuppression, and postoperative prevention of arterial complications and compared it with current recommendations.

The organization of perioperative LT care involved 1 single team throughout the perioperative LT process in 7 centers (43.7%). The coronary evaluation was systematic in one-third of the centers and guided by risk factors in the other centers. Antibiotic prophylaxis was strictly intraoperative in only 7 centers (44%). Antifungal prophylaxis targeting high-risk LT recipients was administered in 15 centers (93%). Intraoperative coagulation assessment was based on standard coagulation tests in 8 centers (50%), on viscoelastic assays in 4 centers (25%), and both methods in 4 centers (25%). Hemodynamic monitoring practices greatly varied between centers.Concerning immunosuppression, molecules and dosages were heterogeneous. Aspirin was systematically administered in one-third of cases (6 centers; 37.5%). Of the 21 recommendations tested, the concordance rate was 100% for 3 recommendations and <50% for 7 recommendations.

Our study precisely describes French practices regarding LT in perioperative care and highlights the paucity of data in this setting, leading to very weak recommendations that are poorly followed in LT centers.

To elucidate the demographics, clinical characteristics, and outcomes of patients with postpartum hemorrhage (PPH) who underwent transcatheter arterial embolization (TAE).

We conducted a retrospective observational study using the Japanese Diagnosis Procedure Combination inpatient database, which covers roughly 90% of all tertiary emergency hospitals in Japan, between April 2012 to March 2020. We identified patients with PPH who underwent TAE using the Japanese medical procedure status and code, and the device or drug code. We examined the patient characteristics, interventions administered, and clinical outcomes.

Among 64 893 patients diagnosed with PPH, we identified 2705 (4.2%) patients with PPH who underwent TAE. The most common cause of PPH was uterine atony (68.7%), followed by disseminated intravascular coagulation after labor (30.0%) and placenta accreta spectrum disorders (23.4%). The proportion of patients who underwent repeat TAE and a hysterectomy was 64 (2.4%) and 188 (7.0%), respectively. Among hysterectomies (n = 188), 26 (13.8%) had the procedure performed before TAE, 73 (38.8%) underwent hysterectomy on the same day as TAE, and 89 (47.4%) had the procedure conducted after TAE. Of those who underwent a hysterectomy after TAE (n = 89), 33 (37%) were performed more than 1-week after initial TAE. Overall in-hospital mortality was 14/2705 (0.5%).

Even if hemostasis is achieved through TAE, one must be mindful that a hysterectomy may become necessary more than 1 week after the procedure. These results could be helpful in clinical decision making and providing patients with additional treatment options for PPH that preserve patient fertility.

Alongside health consequences, cesarean delivery (CD) has been associated with increased healthcare resource utilization (HCRU). A CD should be performed in case of placenta previa; in turn, the most appropriate mode of birth in women with a low-lying placenta (LLP) is still controversial. Since no previous data are available on the topic, the aim of this study was to evaluate the HCRU and economic impact on the Italian HC system of vaginal birth (VB) and CD in women with a LLP.

This retrospective study used patient-level real-world data of a cohort of women with a LLP confirmed at 28-30 weeks. A cost-minimization analysis (CMA) was conducted to compare VB and CD. Since Diagnosis-Related-Group payment may not reflect the actual use of hospital resources, a micro-costing analysis (MCA) was performed to more comprehensively evaluate the economic impact of VB and CD.

The study included 86 women with a LLP at the third trimester scan, of which 49 (57%) had a VB and 37 (43%) underwent a CD. The CMA showed an economically marginal difference between VB and CD, especially when considering opportunity costs associated with the resources needed to look after women. However, the MCA identified charges for each VB being about half of those for each CD.

The use of patient-level real-world data allowed to generate basic information to assess the value of available interventions in case of LLP. A VB should be promoted in women with LLP, avoiding further burden on the HC system's limited resources.

Emergency department (ED) use is common among patients with Medicaid insurance during pregnancy. However, it is unknown how ED utilization differs among those with different types of Medicaid such as Emergency Medicaid, with which access to outpatient care is more restricted.

We sought to compare differences in ED use during between pregnant persons with Emergency Medicaid and Traditional Medicaid and pregnancy outcomes by ED utilization.

This was a retrospective cohort study of all births among Medicaid enrollees in South Carolina from 2010 to 2019. The main comparator was type of Medicaid. Our primary outcome was an ED visit during pregnancy. Secondary outcomes included average number of visits, perinatal outcomes, and prenatal and hospital charges.

There were 240,597 births that met inclusion criteria for this analysis. Over the study period, the proportion of patients with at least one ED visit increased for all groups. A higher proportion of patients with Traditional Medicaid had at least one ED visit compared with Emergency Medicaid (58.2% versus 22.7%). Patients who had at least one ED visit were more likely to be younger, of Black race, live rurally, nulliparous, have lower or higher body mass index, and have a higher prevalence of pre-existing medical co-morbidities.

We found that individuals with Traditional Medicaid were more likely to have an antenatal ED visit than individuals with Emergency Medicaid.

Bleeding complications, such as hematoma, are frequently encountered after breast surgery. To mitigate these complications, the use of tranexamic acid (TXA), has become increasingly popular in breast procedures. This study aims to investigate the impact of topical moistening of the surgical wound with TXA on the reduction of postoperative bleeding complications in patients undergoing gender-affirming mastectomy (GAM).

A single-center retrospective cohort study examined postoperative bleeding outcomes in patients who underwent GAM between April 2014 and March 2024. The use of intraoperative topical TXA was documented, along with rates of hematoma, seroma, and other postoperative complications.

The study included 456 patients: 62 who received topical moistening with 10 mL of 50 mg/mL TXA on each breast and 394 control patients who received standard hospital protocol for intraoperative hemostasis. Postoperative hematoma occurred in 3 patients (4.9%) who received topical TXA and 18 patients (4.6%) who did not (p=0.92). The incidence of other postoperative complications did not significantly differ between the groups.

This study found no statistically significant differences in postoperative bleeding complication rates between patients who received TXA and those who followed the standard hemostasis protocol. Although our results suggest that topical TXA is safe and does not increase thromboembolic risk, its efficacy in reducing bleeding complications in GAM patients remains uncertain. The study's limitations, including its single-center design and small sample size, highlight the need for larger, multicenter randomized trials to establish the role of topical TXA in improving postoperative outcomes for GAM procedures.

To determine structural and process readiness for postpartum haemorrhage (PPH) care at referral-level facilities in Ghana and Uganda to identify opportunities for strengthening.

Mixed-methods cross-sectional study.

Three districts in Ghana and two in Uganda.

Nine hospitals in Ghana and seven in Uganda; all hospitals had theoretical capacity for caesarean section and blood transfusion.

We deployed a modular quantitative health facility assessment to explore structural readiness (drugs, equipment, staff) complemented by in-depth interviews with maternity health service providers to understand process readiness (knowledge, attitudes, and practices as related to World Health Organization [WHO] guidance on PPH care).

Availability of essential structural components needed to support key PPH processes of care.

In both countries, there was generally good structural readiness for PPH care. However, key common gaps included inadequate staffing (especially specialist physicians), and unavailability of blood for transfusion. Interviews highlighted particularly good process readiness in the provision of uterotonics, recognising and responding to retained placenta, and repairing tears. However, there were clear gaps in the utilisation of tranexamic acid and uterine balloon tamponade.

We have identified good structural and process readiness across both Ghanaian and Ugandan health facilities to support PPH responses. However, some key missed opportunities-to align with current WHO guidance on providing bundles of interventions for PPH care-could be strengthened with minimal investment but promising impact.

Tranexamic acid (TXA) is an antifibrinolytic agent with promising benefits in facial rejuvenation surgery. The best way to administer this medication for therapeutic value is currently unknown. This study compared outcomes for facelift patients given TXA intravenously versus locally in tumescent solution.

Sixty rhytidectomy patients were randomized to receive 1 g of TXA intravenously or 150 mg of TXA in facial tumescent. Blood loss and surgeon-assigned bleeding rate were recorded intraoperatively for each side of the face. On postoperative day 7, patients assessed surgical satisfaction and bruising and swelling levels, and the surgeon graded ecchymosis and edema. Time to drain removal and complication incidence were also documented.

Mean blood loss was 25.86 mL for intravenous (IV) TXA patients versus 30.00 mL for local patients (P = 0.23) on side 1. On side 2, average blood loss was 30.00 mL in the IV group and 35.54 mL in the local group (P = 0.51). The median bruising and swelling rating was 2 for IV patients and 3 for local patients (P = 0.14). The groups had equivalent median blood loss scores, satisfaction ratings, ecchymosis and edema ratings, and complication rates. Mean days to drain removal were lower in the IV TXA group (1.16 versus 2.04 d, P = 0.04). The local TXA group had significantly more variation in patient satisfaction (P = 0.04) and time to drain removal (P < 0.001).

IV administration of TXA may have a slight advantage over local infiltration as it decreases days to drain removal and yields more precise outcomes for patient satisfaction and time to drain removal.

Despite robust supporting evidence, around a third of eligible surgical patients do not receive tranexamic acid (TXA). Effective strategies based on an understanding of clinical behaviour are needed to increase use and improve patient outcomes. We conducted semi-structured interviews with clinicians involved in perioperative care to explore perceived influences on TXA use. We identified key influences on practice using the theoretical domains framework. We matched these to behaviour change techniques and evidence-informed implementation intervention components. Across 22 interviews, we identified eight key influences within three overarching themes of capability, opportunity and motivation. Capability influences included the clinical context and variable familiarity with TXA. Opportunity concerned the availability of both TXA and checklists to support decision-making and whether TXA use was consistent with professional expectations and perceived responsibilities. Motivation concerned confidence in administering TXA, perceived benefits and risks and training received around potential risk factors. These influences varied across participants and specialities. Our resulting proposed implementation strategy included training, clinical prompts, comparative performance feedback and opinion leadership supported by specialty-specific guidance. Any strategy to increase TXA use that improves knowledge and skills without addressing wider influences on clinical behaviour is only likely to meet with limited success.

Perioperative bleeding is common in general surgery. The POISE-3 (Perioperative Ischemic Evaluation-3) trial demonstrated efficacy of prophylactic tranexamic acid (TXA) compared with placebo in preventing major bleeding without increasing vascular outcomes in noncardiac surgery.

To determine the safety and efficacy of prophylactic TXA, specifically in general surgery.

Subgroup analyses were conducted that compared randomized treatment with TXA vs placebo according to whether patients underwent general surgery or nongeneral surgery in the POISE-3 blinded, international, multicenter randomized clinical trial. Participants were 45 years or older, were undergoing noncardiac surgery, had increased cardiovascular risk, and were expected to require at least an overnight hospital admission after surgery. Among 26 581 eligible patients identified, 17 046 were excluded, resulting in 9535 patients randomized to the POISE-3 trial. Participants were enrolled from June 2018 through July 2021. The data were analyzed during December 2023.

Prophylactic, 1-g bolus of intravenous TXA or placebo at the start and end of surgery.

The primary efficacy outcome was a composite of life-threatening bleeding, major bleeding, or bleeding into a critical organ. The primary safety outcome was a composite of myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism at 30 days. Cox proportional hazards models were conducted, incorporating tests of interaction.

Among 9535 POISE-3 participants, 3260 underwent a general surgery procedure. Mean age was 68.6 (SD, 9.6) years, 1740 were male (53.4%), and 1520 were female (46.6%). Among general surgery patients, 8.0% and 10.5% in the TXA and placebo groups, respectively, had the primary efficacy outcome (hazard ratio [HR], 0.74; 95% CI, 0.59-0.93; P = .01) and 11.9% and 12.5% in the TXA and placebo groups, respectively, had the primary safety outcome (HR, 0.95; 95% CI, 0.78-1.16; P = .63). There was no significant interaction by type of surgery (general surgery vs nongeneral surgery) on the primary efficacy (P for interaction = .81) and safety (P for interaction = .37) outcomes. Across subtypes of general surgery, TXA decreased the composite bleeding outcome in hepatopancreaticobiliary surgery (HR, 0.55; 95% CI, 0.34-0.91 [n = 332]) and colorectal surgery (HR, 0.67; 95% CI, 0.45-0.98 [n = 940]). There was no significant interaction across subtypes of general surgery (P for interaction = .68).

In this study, TXA significantly reduced the risk of perioperative bleeding without increasing cardiovascular risk in patients undergoing general surgery procedures.

ClinicalTrials.gov Identifier: NCT03505723.

Treatment options for angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE) are primarily limited to airway monitoring and protection with intubation. The efficacy of tranexamic acid (TXA) in this context remains poorly understood.

Examine outcomes among patients treated with and without TXA for ACEi-AE.

A retrospective cohort study conducted in two hospitals examined emergency department patients with suspected ACEi-AE from 2017 to 2021. Primary outcomes included intensive care unit (ICU) admission, intubation, days intubated, time to administration of TXA, surgical airway required, and death in patients that received TXA compared with those that did not.

Of 336 eligible patients, 37 received TXA and 299 did not. ICU admission rate was significantly higher in the TXA group (57%) vs. the no-TXA group (15%), odds ratio (OR) 7.61 (95% confidence interval [CI] 3.69-15.70). There were significantly more intubations in the TXA group (20%) vs. the no-TXA group (5.7%), OR 3.87 (95% CI 1.49-10.08). The median time to TXA administration was 51 min (interquartile range 34-131). The number of days intubated, surgical airway, and 30-day mortality were not significantly different in the TXA group compared with the no-TXA group.

TXA use did not improve many of the clinical outcomes involved in the treatment of ACEi-AE. One interpretation of these results may be that TXA use was associated with patients who presented with more severe disease, as TXA use was up to the discretion of the treating physician. Randomized controlled trials are needed to clarify the efficacy of TXA use in ACEi-AE.

Heavy menstrual bleeding (HMB) is a significant clinical burden for premenopausal individuals treated with anticoagulation for acute venous thromboembolism (VTE). Despite its prevalence, HMB management remains poorly studied, with wide variation in clinical practice.

The current study aimed to explore current UK practices in managing HMB in anticoagulated individuals and identify areas requiring clinical research to address disparities.

A national survey was conducted among haematology consultants and consultant clinical pharmacists managing anticoagulated patients. The survey focused on management strategies, including anticoagulant selection, use of tranexamic acid (TXA), contraceptive options, and anticoagulation interruption.

Responses were collected from 102 participants, across the UK. Apixaban was the preferred anticoagulant for patients with HMB, followed by LMWH then dabigatran. Timing of TXA initiation varied widely between respondents, with (35.3 %) prescribing it any time after anticoagulation initiation, (11.8 %) delaying TXA use for 3 months, and (7.8 %) would not give it at all. (47.1 %) of respondents advise to discontinue oestrogen containing contraceptives in patients with acute VTE. Almost all respondents never or rarely stop anticoagulation for a patient with HMB and recent VTE ≤4 weeks. (62.7 %) of respondents showed their willingness to participate in clinical studies to study TXA use in the setting of acute VTE ≤4 weeks in anticoagulated individuals. This study highlights significant variations in HMB management during anticoagulation for acute VTE. Disparities raise concerns about health inequities and underscore the urgent need for prospective clinical trials to improve patient outcomes.

Tranexamic acid is an anti-fibrinolytic drug recommended in the setting of post-partum hemorrhage and non-obstetrical massive bleeding. Its putative role in the pathogenesis of renal cortical necrosis is unclear and has been rarely reported.

We report the case of a young woman who developed anuric acute kidney injury upon administration of tranexamic acid in the setting of mild traumatic hemorrhage. Early contrast-enhanced computed tomography revealed diffuse defects of cortical enhancement in both kidneys, consistent with the diagnosis of acute bilateral renal cortical necrosis. Biological tests did not detect hallmarks of thrombotic microangiopathy or disseminated intravascular coagulation and testing for acquired thrombophilic disorders were negative. The patient remained dialysis-dependent for two months and then partially recovered renal function to an estimated glomerular filtration rate of 40 ml/min/1.73 m2.

This case illustrates the potential prothrombotic effect of tranexamic acid administered in the context of non-obstetric acute bleeding and the importance of re-considering its prescription in the presence of concomitant estrogenic impregnation in order to alleviate the risk of occurrence of renal cortical necrosis. It also addresses the predictive value of kidney imaging for the severity of renal cortical necrosis and subsequent renal recovery.

Disseminated intravascular coagulation (DIC) is a complex and serious condition characterized by widespread activation of the coagulation cascade, resulting in both thrombosis and bleeding. This review aims to provide a comprehensive overview of DIC, emphasizing its clinical significance and the need for improved management strategies. We explore the primary causes of DIC, including sepsis, trauma, malignancies, and obstetric complications, which trigger an overactive coagulation response. At the molecular level, DIC is marked by excessive thrombin generation, leading to platelet and fibrinogen activation while simultaneously depleting clotting factors, creating a paradoxical bleeding tendency. Diagnosing DIC is challenging and relies on a combination of existing diagnostic criteria and laboratory tests. Treatment strategies focus on addressing the underlying causes and may involve supportive care, anticoagulation therapy, and other supportive measures. Recent advances in understanding the pathophysiology of DIC are paving the way for more targeted therapeutic approaches. This review highlights the critical need for ongoing research to enhance diagnostic accuracy and treatment efficacy, ultimately improving patient outcomes in those affected by DIC.

Nearly 4% of pregnant patients have an injury-related visit to the emergency department during their pregnancy. There are important physiologic changes that occur during pregnancy that make managing pregnant trauma patients different from the standard management of a nonpregnant patient. This review discusses these changes and the initial assessment, laboratory, and imaging workups for the pregnant trauma patient. In addition, management of specific injuries in pregnancy including pelvic fractures, hemorrhagic shock, and postpartum hemorrhage are reviewed as well as key points regarding resuscitative hysterotomy and fetal support that trauma surgeons should be aware of.

The 2022 national guideline on The Prevention and Management of Primary Postpartum Haemorrhage (PPH) recommended consideration of prophylactic tranexamic acid (TXA) for women who are at high PPH risk undergoing caesarean section (CS). This meta-analysis reviews the basis for this recommendation.

PubMed, OVID Medline, EMBASE, Science Citation Index, Scopus, CENTRAL, and ClinicalTrials.gov were searched (from inception to January 2024) for randomised controlled trials comparing prophylactic intravenous TXA with placebo or no treatment in women undergoing CS who received a uterotonic. Our main outcome was PPH > 1L. Secondary outcomes included estimated mean blood loss, blood transfusion, drop in haemoglobin, the need for additional uterotonics, or surgical intervention. Adverse effects of TXA were also assessed.

Sixty-one studies including 25,098 women were identified, and 12,446 received prophylactic TXA. Patients who received prophylactic TXA had significantly reduced likelihood of PPH > 1L (RR, 0.47; 95% CI, 0.38 to 0.59), reduced estimated mean blood loss (MD 185.86 ml, 95% CI 159.14-212.59), and reduced drop in Hb (MD 0.84g/dl, 95% CI 0.72, 0.95). There was a significant reduction in need for additional uterotonics (RR 0.47, 95% CI 0.39-0.57) or surgical intervention (RR 0.54, 95% CI 0.30-0.95).

The reduced risk of PPH > 1L was greatest in patients at higher risk of bleeding. The greatest risk reduction was seen in smaller studies and in studies undertaken in developing economies. Prophylactic TXA administration is effective at reducing the incidence of PPH > 1L at CS. The clinical benefit of universal prophylaxis is questionable; women who are high risk of PPH are more likely to derive benefit.

Delayed post-polypectomy bleeding (DPPB) can occur up to a month following the procedure but is typically seen within the first week. Tranexamic acid (TXA) is a member of a class of drugs called antifibrinolytic agents. It reduces fibrinolysis by slowing down the conversion of plasminogen to plasmin, which may prevent bleeding. The goal of this pilot study is to assess the feasibility of using tranexamic acid after endoscopic mucosal resection (EMR) of large (≥2 cm) non-pedunculated colorectal polyps (LNPCPs) to prevent DPPB.

This was a single centre feasibility study conducted at the Kingston Health Sciences Centre in 2021. After the polypectomy was completed, IV tranexamic acid was given [1 gram of TXA in 100 mL of normal saline] and infused over a 10-min interval. The participants received tranexamic acid 1 gram PO TID to be taken for 5 days.

A total of 25 patients were enrolled with a mean polyp size of 3 cm. Intraprocedural bleeding occurred in 7 patients (28%) and all of these were treated with soft coagulation. Two patients had clipping for suspected muscle injury. All 25 patients received IV TXA post-procedure. Sixteen patients (64%) took every dose of the prescribed pills. One patient presented with post-polypectomy bleeding. All patients completed the day 30 follow-up phone call. There were no major adverse events.

TXA to prevent delayed post-polypectomy bleeding (DPPB) was feasible to use with no major adverse events reported. A randomized controlled study will be needed to see if TXA can significantly reduce DPPB.

A state of the art lecture titled, "Addressing the Perimenopause: What's Blood Got to Do with It?" was presented at the International Society on Haemostasis and Thrombosis (ISTH) Congress in 2024. Perimenopause is when fluctuations of previously cyclically regulated hormones occur prior to menopause, resulting in a number of symptoms that can negatively impact a woman's quality of life. Thrombosis and hemostasis experts are often approached to help investigate and manage clinical issues associated with perimenopause. This includes the safety of using menopause hormonal therapy in a past history or family history of venous thromboembolism, arterial thrombosis or thrombophilia, heavy menstrual bleeding, and iron deficiency anemia. A review of recent literature and clinical practice guidelines was undertaken to help determine the role of iron deficiency anemia in perimenopause, thrombotic risk in the setting of using menopause hormonal therapy, and indications for thrombophilia testing prior to commencing menopause hormonal therapy. Finally, we summarize relevant new data on this topic presented during the ISTH 2024 Congress.

Dysregulations of blood clot breakdown (fibrinolysis) during vascular trauma can lead to excessive blood loss. Tranexamic acid (TXA) is an inhibitor of fibrinolysis that works by blocking the interaction between plasminogen and fibrin degradation products (FDPs) - a key step in fibrinolysis. Despite the widespread usage, there are no tests available in a clinical setting to monitor TXA levels. We developed a fluorescence resonance energy transfer (FRET)-based assay to quantify TXA concentrations in plasma by using 1) fluorescently labeled plasminogen, and 2) FDPs labeled with a fluorescence quencher. Once plasminogen binds the FDPs, the fluorescent signal is quenched. TXA causes plasminogen to dissociate from the FDPs, thus increasing fluorescence signal in a dose-dependent manner. The dose response was sensitive between 1 and 100 μM (0.16 and 15.7 mg/L). The intraassay and interassay variabilities were determined to be 5.7 % and 3.0 %, respectively. Limit of detection was estimated to be 0.28 μM (0.044 mg/L). When tested for measuring known levels of TXA added to plasma samples, the ratio between measured and expected TXA concentration was 1.0151. Our study demonstrates a novel assay that can rapidly quantify TXA concentrations in plasma samples, thus demonstrating its potential as an in-hospital tool.

 The World Health Organization recommends tranexamic acid (TXA) in the management of postpartum hemorrhage (PPH). However, the role of TXA in PPH prevention and the optimal timing of TXA administration remain unknown. Our objective was to describe the timing of TXA administration, differences in timing of TXA administration by mode of delivery, and current trends in TXA administration in the United States.

 We conducted a descriptive study of trends in TXA administration using the Cerner Real-World Database. We identified 1,544,712 deliveries occurring at greater than 24 weeks' gestation from January 1, 2016, to February 21, 2023. Demographic data were collected including gestational age, mode of delivery, and comorbidities. The timing of TXA administration and differences in TXA timing by mode of delivery were also collected.

 In our cohort, 21,433 patients (1.39%) received TXA. The majority of patients who received TXA were between ages 25 and 34 years old (55.3%), White (60.7%), and delivered between 37 and 416/7 weeks (81.4%). The TXA group had a higher prevalence of medical comorbidities including obesity (32.9 vs. 19.0%, p < 0.00001), preeclampsia (19.6 vs. 6.81%, p < 0.00001), and pregestational diabetes (3.27 vs. 1.36%, p < 0.00001). Among women who received TXA, 15.4% received it within 3 hours before delivery. Among patients who received TXA after delivery, 23.6% received TXA within 3 hours after delivery, whereas 35.7% received TXA between 10 and 24 hours after delivery. A total of 80.4% of patients who received TXA before delivery had a cesarean delivery.

 While TXA is most commonly administered after delivery, many patients are receiving TXA prior to delivery in the United States without clear evidence to guide the timing of administration. A randomized trial is urgently needed to determine the safety and efficacy of TXA when administered prior to delivery.

· TXA is used in the treatment of PPH.. · The role of TXA in prevention of PPH is unclear.. · Fewer than 2% of patients in the United States receive TXA at delivery.. · TXA administration before delivery in the United States is rising..

The Spanish enhanced recovery in adult surgery strategy, the "RICA pathway", was published in 2021 and includes 19 specific recommendations and more than 20 indirect recommendations for patient blood management (PBM). After reviewing these recommendations, and in the context of the new clinical evidence available, we propose the following updates: First: Detection and treatment of any preoperative anemia status in ALL patients who are candidates for major surgery with hematinic deficiencies. Second: Universal use of tranexamic acid in major surgery, bedside monitoring of intraoperative hemoglobin levels, restrictive transfusion criteria, and monitoring of patient well-being in terms of hydration, coagulability, normothermia and analgesia. Third: Restrictive transfusion criteria, single-unit blood transfusion and diagnosis/treatment of postoperative anemia. Real, universal implementation and integration of PBM in the RICA program is urgently needed.

Non-compressible torso hemorrhage (NCTH) represents a leading cause of preventable mortality in trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) stabilizes NCTH but may predispose patients to thrombus generation. REBOA must therefore be prospectively evaluated for coagulation risks with concomitant usage of anti-fibrinolytic tranexamic acid (TXA). Using a porcine model of hemorrhage, it was hypothesized that TXA with REBOA would worsen coagulation outcomes and organ damage.

Thirty-two male Yorkshire swine underwent 30% blood volume hemorrhage with randomization to vehicle control (VC; normal saline), VC+REBOA, TXA, or TXA+REBOA. At T0, animals received 10 mL/minute of group-specific infusion (GSI) followed at T10 by 500 mL of whole blood (WB), second GSI at 13 mL/hour, and Zone 1 REBOA inflation in REBOA groups. At T40, REBOA was deflated, with additional 500 mL WB, and continuation of GSI for 3 hours. Physiological, coagulation, and inflammatory parameters were measured throughout the protocol, with postmortem histopathology.

After REBOA deflation at T40, lactate was significantly higher for the REBOA groups versus the non-REBOA groups, and pH, bicarbonate, and base excess were all significantly lower than the non-REBOA groups. There were no significant differences observed between groups in coagulation, inflammatory, metabolic, or histopathologic parameters.

Administration of TXA with REBOA did not cause more deleterious coagulation outcomes. All significant changes were expected results of REBOA ischemia, and not attributable to TXA treatment. This suggests NCTH can safely be treated with both hemorrhage control methods without exacerbating clotting outcomes.

Not applicable-basic animal research.

Liposuction is the most frequently performed cosmetic procedure. Tranexamic acid (TXA) has emerged as a promising blood loss reducing agent in plastic surgery, but its value in liposuction is still being studied. This systematic review investigates the safety and efficacy of TXA in reducing blood loss during liposuction procedures. A systematic review of PubMed, EMBASE, and Cochrane databases from inception to June 2023 was performed. The primary objective was to compare blood loss, hematoma rate, and ecchymosis from liposuction procedures in patients who received TXA with those who did not. The secondary objective was to assess the incidence of TXA-related complications. A total of 9 studies were included, published between 2018 and 2023, of which 8 were prospective and 1 was retrospective. A total of 345 intervention vs 268 control arms were compared. Follow-up time ranged from 1 to 14 days. Mean age and mean BMI ranged from 33 to 50 years and 23 to 30 kg/m2, respectively. Blood loss in aspirate was significantly less with TXA administration as assessed in 5 studies (P < .05). Of the 5 studies that described assessment of the incidence of ecchymosis, all reported less bruising with TXA use. Among all the studies, only 1 reported postoperative complications in 5 patients requiring transfusion in the control group (without TXA). The evidence provided in the literature suggests that TXA administration in liposuction is safe and effective for reducing blood loss and ecchymosis by both intravenous and local administration.

Postpartum haemorrhage (PPH) is common and potentially life-threatening. The antifibrinolytic drug tranexamic acid (TXA) is thought to be effective for treating PPH. There is growing interest in whether TXA is effective for preventing PPH after vaginal birth. In randomised controlled trials (RCTs), TXA has been associated with increased risk of seizures and unexplained increased mortality when given more than three hours after traumatic bleeding. Reliable evidence on the effects, cost-effectiveness and safety of prophylactic TXA is required before considering widespread use. This review updates one published in 2015.

To assess the effects of TXA for preventing PPH compared to placebo or no treatment (with or without uterotonic co-treatment) in women following vaginal birth.

We searched MEDLINE, Embase, CENTRAL, and WHO ICTRP (to 6 September 2024). We also searched reference lists of retrieved studies.

We included RCTs evaluating TXA alone or in addition to standard care (uterotonics) for preventing PPH following vaginal birth. For this update, we required trials to be prospectively registered (before participant recruitment), and we applied a trustworthiness checklist.

Critical outcomes were blood loss ≥ 500 mL and blood loss ≥ 1000 mL. Important outcomes included maternal death, severe morbidity, blood transfusion, receipt of additional surgical interventions to control PPH, thromboembolic events, receipt of additional uterotonics, hysterectomy, and maternal satisfaction.

We used the Cochrane risk of bias tool (RoB 1) to assess the risk of bias in the studies.

Two review authors independently selected trials, extracted data, assessed risk of bias, and assessed trial trustworthiness. We used random-effects meta-analysis to combine data. We assessed the certainty of the evidence using GRADE.

We included three RCTs with 18,974 participants in total. The trials were conducted in both high- and low-resource settings and involved participants at both low and high risk of PPH. The trials compared intravenous TXA (1 g) and standard care versus placebo (saline) and standard care. After applying our trustworthiness checklist, we did not include any of the 12 trials in the previous version of this review.

Prophylactic tranexamic acid in addition to standard care compared to placebo in addition to standard care TXA results in little to no difference in blood loss ≥ 500 mL (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; 2 studies, 18,897 participants; 5 fewer per 1000, 95% CI 15 fewer to 5 more; high-certainty evidence). TXA likely results in little to no difference in blood loss ≥ 1000 mL (RR 0.86, 95% CI 0.69 to 1.07; 2 studies, 18,897 participants; 3 fewer per 1000, 95% CI 6 fewer to 1 more; moderate-certainty evidence). TXA likely results in little to no difference in severe morbidity (RR 0.88, 95% CI 0.69 to 1.12; 1 study, 15,066 participants; 2 fewer per 1000, 95% CI 6 fewer to 2 more; moderate-certainty evidence). TXA results in little to no difference in receipt of blood transfusion (RR 1.00, 95% CI 0.95 to 1.06; 3 studies, 18,972 participants; 0 fewer per 1000, 95% CI 10 fewer to 12 more; high-certainty evidence). TXA may result in little to no difference in receipt of additional surgical interventions to control PPH (RR 0.63, 95% CI 0.32 to 1.23; 2 studies, 18,972 participants; 1 fewer per 1000, 95% CI 2 fewer to 1 more; low-certainty evidence). In women with anaemia, TXA results in little to no difference in receipt of additional uterotonics (RR 1.02, 95% CI 0.94 to 1.10; 1 study, 15,066 participants; 3 more women per 1000, 95% CI 8 fewer to 24 more; high-certainty evidence). In women with no anaemia, TXA results in a slight reduction in receipt of additional uterotonics (RR 0.75, 95% CI 0.61 to 0.92; 1 study, 3891 participants; 24 fewer women per 1000, 95% CI 38 fewer to 8 fewer; high-certainty evidence). TXA likely results in little to no difference in maternal satisfaction. The evidence is very uncertain about the effect of TXA on maternal death, thromboembolic events, and hysterectomy (very low-certainty evidence): maternal death (RR 0.99, 95% CI 0.39 to 2.49; 2 studies, 15,081 participants; 0 fewer per 1000, 95% CI 1 fewer to 2 more); thromboembolic events (RR 0.25, 95% CI 0.03 to 2.24; 3 studies, 18,774 participants; 3 fewer women per 10,000, 95% CI 4 fewer to 5 more); hysterectomy (RR 0.89, 95% CI 0.36 to 2.19; 1 study, 15,066 participants; 1 fewer women per 10,000, 95% CI 9 fewer to 16 more).

Adding prophylactic TXA to standard care of women during vaginal birth makes little to no difference to blood loss ≥ 500 mL and likely makes little to no difference to blood loss ≥ 1000 mL or the risk of severe morbidity, compared to placebo and standard care. TXA may result in little to no difference in additional surgical interventions to control PPH and results in little to no difference in blood transfusions. One trial found that TXA reduced the use of additional uterotonics in women without anaemia, whereas the largest trial found little to no difference in the use of additional uterotonics in women with anaemia. Although there were very few serious adverse events reported, the evidence is insufficient to draw conclusions about the effect of TXA on maternal death, thromboembolic events, hysterectomy, or seizures. TXA likely results in little to no difference in maternal satisfaction. These findings are based mainly on two large trials. In the smaller of these, less than 30% of study participants were at high risk of PPH. In the largest trial, all participants had moderate to severe anaemia. Those making decisions about routine administration of prophylactic TXA for all women having vaginal births should consider that current evidence does not show a benefit of TXA for blood loss outcomes and related morbidity, and the evidence is very uncertain about serious adverse events.

This review was partially funded by the World Health Organization (WHO).

Protocol (2009) DOI: 10.1002/14651858.CD007872 Original review (2010) DOI: 10.1002/14651858.CD007872.pub2 Review update (2015) DOI: 10.1002/14651858.CD007872.pub3.

Platelet transfusions, used as prophylaxis or treatment for bleeding, are potentially life-saving. In many countries, demand for platelet transfusion is rising. Platelets are a limited and costly resource, and it is vital that they are used appropriately. This study will explore the evidence behind platelet transfusions in different contexts, in particular recent and important research in this area.

Recent randomized clinical trials demonstrate the efficacy of platelet transfusions in some contexts but potential detrimental effects in others. Platelet transfusions also carry risk of transfusion reactions, bacterial contamination and platelet transfusion refractoriness. Observational and clinical studies, which highlight approaches to mitigate these risks, will be discussed. There is growing interest in cold-stored or cryopreserved platelet units, which may improve platelet function and availability. Clinical trials also highlight the efficacy of other supportive measures such as tranexamic acid or thrombopoietin receptor agonists in patients with bleeding.

Although platelet transfusions are beneficial in many patients, there remain many settings in which the optimal use of platelet transfusions is unclear, and some situations in which they may have detrimental effects. Future clinical trials are needed to determine optimal use of platelet transfusions in different patient populations.

Ghrelin exerts widespread effects in several diseases, but its role and mechanism in Acute Traumatic Coagulopathy (ATC) are largely unknown. The effect of ghrelin on cell proliferation was examined using three assays: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), Lactate Dehydrogenase (LDH), and flow cytometry. The barrier function of the endothelial cells was evaluated using the Trans-Endothelial Electrical Resistance (TEER) and the endothelial permeability assay. An ATC mouse model was established to evaluate the in vivo effects of ghrelin. The Ras homolog family member A (RhoA) overexpression plasmid or adenovirus was used to examine the molecular mechanism of ghrelin. Ghrelin enhanced Human Umbilical Vein Endothelial Cells (HUVEC) proliferation and endothelial cell barrier function and inhibited HUVEC permeability damage in vitro. Additionally, ghrelin decreased the activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT) in mice blood samples in the ATC mouse model. Ghrelin also improved the pathological alterations in postcava. Mechanistically, ghrelin acts through the RhoA/ Rho-associated Coiled-coil Containing Kinases (ROCK)/ Myosin Light Chain 2 (MLC2) pathway. Furthermore, the protective effects of ghrelin, both in vitro and in vivo, were reversed by RhoA overexpression. Our findings demonstrate that ghrelin may reduce vascular endothelial cell damage and endothelial barrier dysfunction by blocking the RhoA pathway, suggesting that ghrelin may serve as a potential therapeutic target for ATC treatment.