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.

Perioperative blood management strategies include evidence-based guidelines to efficiently manage blood products and transfusions while minimizing blood loss and improving patient outcomes. Perioperative Medicine has made evident that anemia is often under-recognized and not appropriately addressed prior to surgery. Early recognition and correction of anemia is imperative for better surgical optimization, fewer transfusions perioperatively, and improved outcomes. Patient blood management utilize evidence-based guidelines for the establishment of a framework to promote treatment of the causes of anemia, reduce blood loss and coagulopathy as well as to improve patient safety and outcomes by efficiently managing blood products, decrease complications associated with blood transfusions and reduce overall costs. Both liberal and restrictive strategies for blood transfusions established thresholds for hemoglobin: restrictive transfusion threshold of hemoglobin 7-8 g/dL in stable patients, and a higher transfusion threshold of hemoglobin > 8 g/dL may be considered in patients with cardiac disease. Intraoperatively, tests such as viscoelastic testing, including rotational thromboelastometry and thrombelastography, offer real-time analysis of a patient's clotting ability, allowing for targeted transfusions of fresh frozen plasma, platelets, cryoprecipitate or antifibrinolytic drugs. Complications associated with blood transfusions include allergic reactions, delayed hemolytic reactions, transfusion related acute lung injury, transfusion-associated circulatory overload, and the transmission of infectious diseases such as Hepatitis B, Hepatitis C, and Human-immunodeficiency virus. This review will discuss the management of blood products for surgical patients in the entire perioperative setting, with specific considerations for the peri-, intra- and post-operative stages.

BackgroundLaparoscopic sleeve gastrectomy (LSG) is the most widely performed bariatric procedure. While advancements like staple line reinforcement (SLR) have reduced hemorrhagic complications, bleeding risks persist. Tranexamic acid (TXA), an antifibrinolytic agent, has shown promise in mitigating bleeding risks in various surgical disciplines, but its efficacy in LSG with SLR remains unexplored. This study aims to evaluate the effect of intraoperative TXA administration on postoperative bleeding outcomes in patients undergoing LSG with oversewing and omentopexy.MethodsThis prospective observational cohort study included 233 patients undergoing LSG with oversewing and omentopexy. Patients were divided into 2 groups: 1 received 1 g of TXA intraoperatively, while the other did not. Hemoglobin differences at 24 and 48 hours postoperatively were the primary outcomes. Secondary outcomes included blood transfusion necessity, re-intervention rates, and 30-day surgical complications.ResultsThere was no statistically significant difference in hemoglobin changes at 24 hours (TXA group: 0.8 ± 0.7 g/dL, 95% CI: 0.67-0.93; control group: 0.9 ± 0.9 g/dL, 95% CI: 0.74-1.06; P = 0.125) or at 48 hours (TXA group: 1.4 ± 1.5 g/dL, 95% CI: 1.12-1.68; control group: 1.5 ± 1.4 g/dL, 95% CI: 1.25-1.75; P = 0.167) between the groups. No patients required transfusions or re-interventions. Five patients in the control group exhibited hemorrhagic drainage exceeding 150 mL, while none in the TXA group experienced similar complications. Length of hospital stay and operative time were similar between the groups (P = 0.124 and 0.746, respectively).ConclusionsTranexamic acid may not significantly impact major bleeding complications following LSG with oversewing and omentopexy but appears to reduce minor hemorrhagic events.

The transfusion of platelets and fresh frozen plasma (FFP) to critically ill neonates in neonatal intensive care units (NICUs) is a common intervention, yet it is still widely performed without adhering to international guidelines. The guidance itself on the therapeutic management of neonatal coagulation disorders is generally limited due to the absence of strong indications for treatment and is mainly aimed at the prevention of major hemorrhagic events such as intraventricular hemorrhage (IVH) in premature neonates. Historically, the underrepresentation of neonates in clinical studies related to transfusion medicine had led to significant gaps in our knowledge regarding the best transfusion practices in this vulnerable group and to a wide variability in policies among different neonatal units, often based on local experience or guidance designed for older children or adults, and possibly increasing the risk of inappropriate or ineffective interventions. Platelet transfusion and, particularly, FFP administration have been linked to potentially fatal complications in neonates and thus any decision needs to be carefully balanced and requires a thorough consideration of multiple factors in the neonatal population. Despite recent advances toward more restrictive practices, platelet and FFP transfusions are still subject to wide variability in practices.This review examines the existing literature on platelet and FFP transfusions and on the management of massive hemorrhage in neonates, provides a summary of evidence-based guidelines on these topics, and highlights current developments and areas for ongoing and future research with the aim of improving clinical practices.

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.

Tranexamic acid (TXA) is an antifibrinolytic that is regularly used to reduce bleeding in surgical specialties.

The objective of this study was to assess the effects of subcutaneous TXA in oculofacial plastic surgeries, with the hypothesis that TXA reduced postoperative ecchymosis and edema.

This was a prospective, randomized, double-blind, split-face study. The sides of the face were randomized to local anesthetic (bupivacaine with epinephrine) mixed with TXA or sodium chloride (placebo). Photographs were taken immediately postoperatively and on postoperative day (POD) 7. Photographs were graded by 2 masked investigators with the Surgeon Periorbital Rating of Edema and Ecchymosis criteria. Patients selected the side that they subjectively determined to have less ecchymosis and edema. As a secondary outcome, patients rated pain on each side of their face with the Wong-Baker FACES pain scale.

Twenty-four patients undergoing bilateral, symmetric oculofacial surgery were included in the study. There was a statistically significant difference in postoperative periocular ecchymosis on POD7 (with TXA .91 ± 0.73 vs placebo 1.61 ± 1.03; P = .020) and in periocular edema on POD1 (with TXA 1.30 ± 0.76 vs placebo 2.00 ± 0.85; P = .028). All patients selected the side of the face receiving TXA as having less periocular ecchymosis and edema. There was no statistically significant difference in subjective pain level between the side receiving TXA vs placebo. There were no intraoperative or postoperative complications.

Subcutaneous TXA was safe and reduced periocular ecchymosis and edema compared to contralateral placebo injections in this series of patients undergoing bilateral oculofacial plastic surgeries.

Multimodal perioperative management is an integrative, holistic approach to optimizing perioperative patient care. The aim is to accelerate postoperative recovery, minimize complications and increase patient satisfaction. This approach combines various strategies that are tailored to the individual needs of patients. A comprehensive preoperative assessment, in particular preoperative individual risk stratification and perioperative medication management, makes it possible to identify risk factors and take targeted measures. Our overview is intended to provide compact information, particularly for the preoperative setting, and to provide suggestions for practice based on the guideline-oriented summary.

Trauma-related injuries account for up to 4.4 million deaths annually worldwide. Failure to identify haemorrhage in trauma patients increases mortality. This study examines the association of central capillary refill time (CRT) and mortality in adult trauma patients, especially in the subgroup with normal heart rate (HR) and blood pressure (BP).

This retrospective observational study analysed data from the CRASH-2 trial, conducted in 274 hospitals across 40 countries and 5 continents between May 2005 and January 2010. A total of 19,054 out of 20,207 adult trauma patients with recorded CRT and complete dataset were included. CRT was taken centrally (sternum) and categorized as ≤ 2, 3-4, and ≥ 5 s. The primary outcome was 28-day mortality, while secondary outcomes included need for transfusion, surgical intervention and thromboembolic events. Univariable and multivariable logistic regression analysis were conducted, incorporating random effects for continent/cluster. Receiver operating characteristic curves were used to assess the discriminatory ability of central CRT measurement.

Among the patients, 6,756 (35.5%) had a CRT ≤ 2 s, 9,142 (48%) had a CRT of 3-4 s, and 3,156 (16.6%) had a CRT ≥ 5 s. Compared to the reference category (CRT ≤ 2 s), the odds of death were significantly higher in patients with CRT of 3-4 s (OR 1.7, 95% CI 1.6-1.9) and CRT ≥ 5 s (OR 3.2, 95% CI 2.8-3.5). Higher CRT was also associated with an increased likelihood of blood transfusion, surgical intervention, and thromboembolic events. The AUC values ranged from 0.63 to 0.74 and were consistent with a significant association between the variables.

Central CRT is associated with increased mortality and adverse outcomes in trauma patients. In bleeding trauma patients, an increasing central CRT is linked to higher mortality risk, with a central CRT ≥ 5 s being particularly predictive of worse outcomes. This also applies to patients with stable vital signs (normal HR and BP), suggesting that CRT may offer additional value as an indicator of hidden hypoperfusion.

Drug repurposing may be an efficient strategy for identifying new cancer treatments. Tranexamic acid (TXA), an antifibrinolytic agent that affects the plasminogen-plasmin pathway, may have potential anticancer effects by influencing tumor cell proliferation, angiogenesis, inflammation, immune response, and tissue remodeling-all crucial processes contributing to tumor progression and metastasis.

Evaluate TXA's anticancer effects across in vitro, animal, and clinical studies to assess its potential as a repurposed cancer drug.

The study was designed as a PRISMA-compliant systematic review and meta-analysis. The literature search was conducted in MEDLINE, EMBASE, Web of Science, and the Cochrane Library. In vitro, animal, and clinical studies investigating the anticancer effects of TXA or epsilon-aminocaproic acid (EACA) were included. Animal and clinical studies were critically appraised, and studies with a low risk of bias were included in the meta-analysis.

Of 4367 identified records, 38 articles were included, collectively reporting findings from 41 in vitro studies, 34 animal studies (n = 843 animals), and seven clinical studies (n = 91 patients). The meta-analysis included nine animal studies and showed a tumor growth reduction in animals treated with TXA compared to controls with a standardized mean difference of - 1.0 (95%CI - 1.5; - 0.4) (p = 0.0002). Equivalently, the majority of in vitro studies reported reduced proliferation, viability, and invasiveness in TXA-exposed tumor cell lines. The clinical studies were considerably susceptible to bias, rendering any conclusions futile.

TXA shows promise as a repurposed cancer drug, revealing an overall reduction in tumor growth, viability, and invasiveness in animal and in vitro studies.

Periorbital ecchymosis and edema are common postoperative concerns in blepharoplasty surgery, negatively impacting recovery and patient satisfaction. Tranexamic acid (TXA), an antifibrinolytic agent, has shown promise in mitigating ecchymosis, but its efficacy and optimal administration route remain uncertain. This systematic review and meta-analysis evaluated the efficacy and safety of intravenous (IV) or subcutaneous TXA in blepharoplasty surgery.

A systematic search was conducted on PubMed, Embase, and Cochrane for randomized controlled trials comparing TXA to no TXA use in blepharoplasty. The primary endpoint was the ecchymosis score, evaluated at postoperative day (POD) 0, POD 1-3, and POD 7-9. Secondary outcomes included time to resume active daily living, operative time, intraoperative pain, and adverse events. Subgroup analysis compared IV and subcutaneous administration.

Five randomized controlled trials comprising 594 patients and 739 eyes were included. TXA significantly reduced ecchymosis scores at POD 0 (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.43 to -0.04; p = 0.02), POD 1-3 (SMD: -0.56; 95% CI: -0.81 to -0.31; p < 0.01), POD 7-9 (SMD: -0.65; 95% CI: -1.12 to -0.17; p < 0.01), and time to resume active daily living (MD: -1.22 days; 95% CI: -1.63 to -0.80; p < 0.01). Subgroup analysis revealed significant differences between subcutaneous (SMD: -0.36; 95% CI: -0.57 to -0.15; p < 0.01) and IV TXA (SMD: -0.97; 95% CI: -1.37 to -0.56; p < 0.01) on ecchymosis at POD 7-9. There were no adverse events related to TXA.

According to the current literature, TXA safely reduces ecchymosis and accelerates recovery in blepharoplasty, with a greater effect of IV administration in the late period. Further, high-quality randomized controlled trials using standardized ecchymosis grading scores are needed to validate these findings.

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.

Background: Death in the early phase of trauma is primarily attributable to uncontrolled bleeding exacerbated by trauma-induced coagulopathy (TIC). A comprehensive synthesis of the available evidence on interventions for TIC is needed. Methods: We conducted a systematic review and meta-analysis of blood component products and tranexamic acid administrations for severe trauma patients with TIC. We included randomized and nonrandomized controlled trials. We included studies with patients who required transfusion with any coagulopathy associated with trauma and a detailed definition. The intervention was administration of blood component products and tranexamic acid. The primary outcome of the study was all-cause mortality and transfusion quantity. Results: Four randomized controlled trials and seven observational studies were included in the qualitative synthesis. In this study, fibrinogen concentrate (FC), prothrombin coagulation cofactor (PCC), and Combination administrations of FC and PCC (FC + PCC) administration did not significantly reduce mortality rates. FC, PCC, and FC + PCC administrations significantly reduced RBC transfusions after admission. In addition, PCC administration reduced FFP transfusions during hospital admission. The incidence of thrombotic events was not significantly higher in the FC + PCC, PCC, and rFVIIa groups. Although statistically nonsignificant, multiple organ failure was lower in the FC and FC + PCC groups. Conclusions: FC and PCC administrations did not significantly reduce mortality. However, FC, PCC, and FC + PCC reduced transfusion rates and complications in patients with coagulopathy-associated trauma. However, the definition of TIC is quite heterogeneous. Thus, the definition of TIC should be defined universally. Furthermore, because of the lack of high certainty of evidence, further well-constructed trials are warranted to investigate the efficacy of blood component products, specifically FC and PCC supplementation for TIC.

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 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.

Mitigating dead space has been recognized as an essential step toward ensuring a more predictable and aesthetically pleasing outcome in rhinoplasty. The current body of literature leaves a discernible gap in offering a unified, systematic approach to dead-space management in rhinoplasty. The aim of this article is to bridge this gap by presenting an integrative approach to surgical and postsurgical techniques.

The aim of this double-blind randomized controlled trial was to evaluate the effects of a two-dose tranexamic acid (TXA) protocol on oedema, bleeding, and surgical field visibility during orthognathic surgery. 72 patients participated and were assigned to three groups: the TXA250 group received a single intravenous dose of 250 mg TXA prior to incision; the TXA500 group received 250 mg TXA before incision and 250 mg after the first jaw surgery was completed; the control group received no TXA. Oedema was measured preoperatively and on postoperative days 1, 3, and 7. Sixty-four patients completed the study. Bleeding was significantly higher and Fromme scale scores for surgical field visibility were significantly lower in the control group compared to the TXA groups (all P < 0.001). The TXA500 group demonstrated significantly reduced oedema compared to the control group (day 3: P = 0.037, day 7: P = 0.002), while the comparison of the TXA250 and control groups showed no significant difference. However, there was no significant difference in oedema between the two TXA groups. Hence, no firm conclusions can be drawn about the superiority of two-dose TXA over the single dose; this needs further investigation in a future study.

Trauma is a leading cause of morbidity and mortality worldwide. Research shows that haemorrhage and trauma-induced coagulopathy are reversible components of traumatic injury, if identified and treated early. Lack of consensus on definitions and transfusion strategies hinders the translation of this evidence into clinical practice.

To assess the beneficial and harmful effects of transfusion strategies started within 24 hours of traumatic injury in adults (aged 16 years and over) with major bleeding.

CENTRAL, MEDLINE, Embase, five other databases, and three trial registers were searched on 20 November 2023. We also checked reference lists of included studies to identify any additional studies.

We included randomised controlled trials (RCTs) of adults (aged 16 years and over) receiving blood products for the management of bleeding within 24 hours of traumatic injury.

We used standard Cochrane methodology to perform the review and assessed the certainty of the evidence using GRADE.

We included 18 RCTs with 5041 participants. Comparison 1: Prehospital transfusion strategies Five studies compared use of plasma (fresh frozen plasma (FFP) or lyophilised plasma) versus 'standard of care'. We are uncertain of the effect of plasma on all-cause mortality at 24 hours (risk ratio (RR) 1.05, 95% confidence interval (CI), 0.48 to 2.30; 3 studies, 279 participants; very low certainty evidence). There is probably no difference between plasma and standard of care in all-cause mortality at 30 days (RR 0.95, 95% CI 0.78 to 1.17; 3 studies, 664 participants; moderate-certainty evidence). However, the results of one cluster-RCT that could not be included in our meta-analysis suggested that plasma may be associated with a lower risk of death at 30 days (RR 0.54, 95% CI 0.42 to 0.70; 1 study, 481 participants; low-certainty evidence). There may be no difference between plasma and standard of care in the total number of thromboembolic events in 30 days (RR 1.23, 95% CI 0.67 to.2.27; 4 studies, 586 participants; low-certainty evidence). Comparison 2: In-hospital transfusion strategies Ten studies evaluated this comparison, seven providing usable data. The studies evaluated cryoprecitate (three studies); fixed-ratio blood component transfusion (three studies); fresh frozen plasma (FFP) (one study); lyophilised plasma (one study); leucoreduced red blood cells (one study); and a restrictive transfusion strategy (one study). All-cause mortality at 24 hours For all-cause mortality at 24 hours, there is probably no difference between: • cryoprecipitate plus a major haemorrhage protocol (MHP) versus MHP alone (RR 0.92, 95% CI 0.70 to 1.21; 1 study, 1577 participants; moderate-certainty evidence); and • blood products (plasma:platelets:red blood cells (RBCs)) transfused in 1:1:1 ratio versus 1:1:2 ratio (RR 0.75, 95% CI 0.52 to 1.08; 1 study, 680 participants; moderate-certainty evidence). We are uncertain of the effect on all-cause mortality at 24 hours for: • blood products (RBCs:FFP) transfused in 1:1 ratio versus transfusion according to coagulation and full blood count results (Peto odds ratio (POR) 0.45, 0.17 to 1.22; 1 study, 434 participants; very low certainty evidence); and • lyophilised (FlyP) plasma versus FFP (POR 1.04, 95% CI 0.06 to 17.23; 1 study, 47 participants; very low certainty evidence); All-cause mortality at 30 days For all-cause mortality at 30 days, there is probably no difference between blood products (plasma:platelets:RBCs) transfused in a 1:1:1 ratio versus a 1:1:2 ratio (RR 0.85, 95% CI 0.65 to 1.11; 1 study, 680 participants; moderate-certainty evidence). There may be little to no difference between the following interventions in all-cause mortality at 30 days: • cryoprecipitate plus MHP versus MHP alone (RR 0.77, 95% CI 0.33 to 1.78; 2 studies, 1572 participants; low-certainty evidence); and •leucoreduced RBCs versus standard RBCs (RR 1.20, 95% CI 0.74 to 1.95; 1 study,55 participants; low certainty evidence). We are uncertain of the effect on all-cause mortality at 30 days for: •lyophilised plasma versus FFP (RR 0.75, 95% CI 0.28 to 2.02; 1 study, 47 participants; very low certainty evidence); and • blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus standard MHP (RR 2.25, 95% CI 0.90 to 5.62; 1 study, 69 participants; very low certainty evidence). Total number of thromboembolic events at 30 days There may be little to no difference between the following interventions for total thromboembolic events at 30 days: • cryoprecipitate plus MHP versus MHP alone (RR 0.55, 95% CI 0.08 to 3.72; 2 studies, 1645 participants; low-certainty evidence); and • blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus 1:1:2 ratio (RR 1.03, 95% CI 0.75 to 1.42; 1 study, 680 participants; low-certainty evidence). We are uncertain of the effect on the total number of thromboembolic events at 30 days for: •blood products (plasma:platelets:RBCs) transfused in 1:1:1 ratio versus standard MHP (POR 6.83, 95% CI 0.68 to 68.35; 1 study, 69 participants; very low certainty evidence). Comparison 3: Whole blood versus individual blood products We are uncertain of the effect of modified (leucoreduced) whole blood versus blood products (RBCs:plasma) transfused in a 1:1 ratio on all-cause mortality at 24 hours (RR 1.13, 95% CI 0.37 to 3.49) or 30 days (RR 1.62, 95% CI 0.69 to 3.80) (1 study, 107 participants; very low certainty evidence). Comparison 4: Goal-directed blood transfusion strategy of viscoelastic haemostatic assay (VHA) versus conventional laboratory coagulation tests (CCT) to guide haemostatic therapy There may be little or no difference in all-cause mortality at 24 hours between VHA and CCT (RR 0.85, 95% CI 0.54 to 1.35; 1 study, 396 participants; low-certainty evidence). We are uncertain of the effects on all-cause mortality at 30 days (RR 0.75, 95% CI 0.48 to 1.17; 2 studies, 506 participants; very low certainty evidence). There is probably no difference between VHA and CCT in total thromboembolic events at 30 days (RR 0.65, 95% CI 0.35 to 1.18; 1 study 396 participants; moderate-certainty evidence).

Overall, there was little to no evidence of a difference between blood transfusion strategies for mortality or thromboembolic events. The studies covered a wide range of interventions, and the comparators and standard of care practice varied between trials, thereby limiting the pooling of data. Further research is needed.

Tranexamic acid (TXA) reduces mortality in severe trauma cases. However, the relationships between TXA administration and coagulation/fibrinolysis abnormalities are unclear. We performed a retrospective observational study to investigate relationships between mortality and coagulation/fibrinolysis abnormalities of patients on arrival at the emergency department and whether TXA is more effective in patients with severe trauma who have coagulation/fibrinolysis abnormalities than in those who do not.

Data was collected from 15 tertiary emergency and critical care centers in Japan. Adult patients with blunt trauma and an Injury Severity Score of ≥ 16 were included in the study. Patients were categorized into two groups: the TXA group received TXA within 3 h of arrival, and the non-TXA group did not.

Overall, 790 patients were included (TXA group, 276; non-TXA group, 514). In cubic spline curves for relationships between mortality and coagulation/fibrinolysis variables on arrival, odds for mortality increased and plateaued with a prothrombin time-international normalized ratio ≥ 1.2; the disseminated intravascular coagulation (DIC) score showed a marked odds increase when > 4 points. Odds increased and plateaued from an activated partial thromboplastin time (APTT) of ≥ 35 s and gradually increased as fibrinogen decreased from 250 mg/dL. Fibrinogen and fibrin degradation products (FDP) and D-dimer exhibited upward-sloping curves. In cubic spline curves for relationships between the effectiveness of TXA administration and coagulation/fibrinolysis variables on arrival, a favorable effect on mortality was observed with TXA administration when fibrinogen was ≤ 200 mg/dL or when the DIC score was ≥ 4 points; FDP, ≥ 50 µg/mL; D-dimer, ≥ 30 µg/mL; or APTT, ≥ 35 s. In each threshold subgroup, interactions between TXA administration and in-hospital mortality were observed.

TXA demonstrates increased effectiveness in patients with traumatic coagulation/fibrinolysis abnormalities.

Systematic review.

To evaluate the statistical robustness of TXA use in spine surgery as a potential contributor to controversies in this field.

Tranexamic acid (TXA) is an antifibrinolytic medication administered during spinal surgery to limit blood loss. Existing randomized controlled trials (RCTs) on the efficacy of TXA contain varied results, particularly when reporting outcomes related to blood transfusion rates and thromboembolic events. By calculating the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ), statistical robustness was quantified and compared across all included RCTs.

PubMed, Embase, and MEDLINE were systematically searched for recent RCTs (January 1, 2000-August 1, 2023) assessing TXA use in patients undergoing spine surgery. The FI and rFI were calculated for each outcome, representing the number of event reversals required to alter statistical significance for significant and nonsignificant outcomes, respectively. The FQ was determined by dividing the FI/rFI by the study sample size.

Of the 297 RCTs screened, 31 studies were included for analysis, yielding 80 dichotomous outcomes. Across these outcomes, the median FI (mFI) was 5.0, with an associated median FQ (mFQ) of 0.060. Nine outcomes were statistically significant (mFQ=0.018), and 71 were nonsignificant (mFQ=0.064). The most common outcome categories included blood/platelet transfusions (38 outcomes), thromboembolic events (15 outcomes), and other adverse events (27 outcomes), resulting in mFQs of 0.056, 0.049, and 0.064, respectively.

Outcomes examining TXA in spinal surgery demonstrated statistical fragility, with significant and thromboembolic outcomes proving the most fragile. Among all outcomes, there was a lack of significant results. To better guide future research on TXA use in spine surgery, this study recommends RCTs report fragility statistics along with P values and include these metrics when proposing clinical implications.

Level III.

The transfusion-sparing strategy in hip prosthetic surgery (Total Hip Arthroplasty, THA) is crucial. Tranexamic Acid (TXA) is a medication whose effectiveness has been demonstrated in numerous surgical indications to reduce bleeding and prevent the risk of blood transfusion.

To evaluate the impact of IV TXA on bleeding in THA for femoral neck fracture (FNF) surgery.

This single-center retrospective cohort study, conducted from January 2020 to September 2021, assessed patients undergoing THA for FNF, comparing those who received 1 g of IV TXA to those who did not, using a matched population through propensity score creation. Analyses were conducted univariately and multivariately.

During the inclusion period, 175 patients underwent THA for FNF, with 87 receiving IV TXA and 88 not receiving TXA. After propensity score matching, the transfusion-free interval was better in the IV TXA treated group (p = 0,03). There was no difference in terms of perioperative bleeding or overall transfusion during hospitalization. There were no differences in the laboratory results at Days 1, 3, and 7.

IV TXA delays the need for transfusion in patients undergoing THA for FNF but does not reduce perioperative bleeding or transfusion during the stay.

IV; retrospective study.

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.

Recent research highlights TXA's potential in managing postoperative bleeding in bariatric surgery, prompting us to evaluate its effectiveness for treatment and prophylaxis. PubMed, Scopus, Cochrane Central, SciElo, and LILACS were searched for TXA studies in bariatric surgery, excluding those without control groups or with overlapping populations. Outcome analysis focused on postoperative bleeding, length of hospital stay (LOS), TXA side effects, mortality, transfusion needs, and thromboembolic complications. From 93 results, six studies involving 1121 patients were included. TXA use significantly decreased the LOS (MD = - 0.12; 95% CI, - 0.18, - 0.06; p < 0.01), operative time (MD = - 5.77; 95% CI, - 9.98, - 1.56; p < 0.01), and postoperative bleeding (OR = 0.57; 95% CI, 0.34, 0.98; p = 0.043). However, TXA did not affect the rate of hematoma formation (OR = 0.39; 95% CI, 0.07, 2.29; p = 0.299), rate of reoperation (OR = 0.46; 95% CI, 0.08, 2.82; p = 0.403), or need for transfusion (OR = 0.25; 95% CI, 0.06, 1.07; p = 0.062). There were no thromboembolic events or mortality. TXA significantly reduces LOS, operative time, and postoperative bleeding in bariatric surgery without affecting reoperation rates. This medication appears to be safe in this population as it did not increase the risk of thromboembolic events.

The treatment of patients with traumatic brain injury (TBI) with subsequently evolving hemostatic failure and hemorrhagic lesion progression remains challenging. New studies highlight windows of opportunity for treatment optimization.

Results from recent randomized studies suggest an earlier treatment with antifibrinolytic tranexamic acid at a higher initial bolus dose. There seems to be a new window of opportunity for the early prehospital use of thawed plasma. Viscoelastic-based goal-directed treatment strategies are still not delivered timely in most patients although a recent meta-analysis has confirmed a survival benefit with this approach.

Mortality in TBI with subsequent evolving hemostatic failure can be reduced through treatment optimization delivering early prehospital high-dose tranexamic acid and in-hospital goal-directed treatment algorithms to timely correct coagulopathy and restore hemostasis.

Tranexamic acid reduces bleeding deaths in trauma patients, but the treatment benefit depends on the time from injury. It is recommended that tranexamic acid be administered immediately and only within 3 h of injury; however, the optimal criteria have not been adequately studied.

We applied machine learning-based causal forest models to investigate heterogeneity in the effects of tranexamic acid on 24-hour mortality rate conditional on covariates (for example age, sex, time from injury, systolic blood pressure, and Glasgow Coma Scale, GCS). We analysed data on 28 448 trauma patients in the CRASH-2 and CRASH-3 randomized trials. We used the policytree algorithm to determine the optimal criteria for tranexamic acid treatment.

The causal forest models showed heterogeneity in the effects of tranexamic acid on 24-hour mortality rate. The relative risk reduction was greatest in patients treated within 2 h of injury but thereafter decreased rapidly. The pattern was similar regardless of age or systolic blood pressure, although with decreasing GCS, the time to treatment effects were weaker, with benefits beyond 3 h. The largest absolute risk reductions were in patients with a low blood pressure and a low GCS when treated soon after injury. The optimal criterion was statistically determined as patients within 2 h of the injury or with GCS < 9.

Tranexamic acid administration was found to be beneficial when given within 2 h of injury. In patients with severe traumatic brain injury, the treatment benefits may persist beyond the 2-hour window.

To investigate the efficacy and safety of high-dose tranexamic acid in different types of surgeries and provide a reference for clinical practice.

We systematically searched PubMed, Cochrane Library, Science, Embase, and CNKI databases, from their inception to January 2025, to include representative literature related to high-dose tranexamic acid in the perioperative period for a thematic synthesis. The analysis focused on clinical evidence related to obstetric, cardiac, urologic, orthopedic, and spinal surgeries.

High-dose tranexamic acid markedly reduces blood loss and transfusion requirements in most types of surgery; however, the optimal dose varies by surgery type. Available studies have shown a favorable safety profile; however, some areas (e.g., cardiac surgery) still require careful monitoring for seizures and risk of thrombotic events.

The clinical benefit of high-dose tranexamic acid should be assessed based on surgical characteristics and patient individualization. More multicenter studies are needed to clarify the dose-effect relationship and long-term safety.

Hemorrhagic shock from traumatic injury results in a massive systemic response with activation of the hypothalamic-pituitary-adrenal (HPA) axis, pro-thrombotic and clot-lysis pathways as well as development of an endotheliopathy. With ongoing hemorrhage, these responses become dysregulated and are associated with worsening coagulopathy, microvascular dysfunction, and increased transfusion requirements. Our transfusion practices as well as our understanding of the molecular response to hemorrhage have undergone significant advancement during war. Currently, resuscitation practices address the benefit of the early recognition and management of acute coagulopathy and advocates for balanced resuscitation with either whole blood or a 1:1 ratio of packed red blood cells to fresh frozen plasma (respectively). However, a significant volume of evidence in the last two decades has recognized the importance of the early modulation of traumatic endotheliopathy and the HPA axis via the early administration of plasma, whole blood, and adjunctive treatments such as tranexamic acid (TXA) and calcium. This evidence compels us to rethink our understanding of 'balanced resuscitation' and begin creating a more structured practice to address additional competing priorities beyond coagulopathy. The following manuscript reviews the benefits of addressing the additional interrelated physiologic responses to hemorrhage and seeks to expand beyond our understanding of 'balanced resuscitation'.

As an anti-fibrinolytic agent, tranexamic acid (TXA) is widely recognized for its efficacy in managing hemorrhagic conditions. Prehospital application of TXA has been reported in recent years, but its benefits in trauma patients remain debated.

A literature search was conducted across databases including PubMed, Cochrane Library, Embase, Web of Science, SCOPUS, and the Cochrane Central Register for Clinical Trials from inception to October 2024, focusing on studies related to prehospital TXA and clinical outcomes in trauma patients. The Cochrane Risk of Bias 2 Tool was applied to assess the quality of randomized control trials (RCTs), while the Newcastle-Ottawa Scale was used for observational cohort studies. Data were pooled under a random- or fixed-effects model using RevMan 5.4 with odds ratio (OR) and 95% confidence interval (CI) as the effect measures.

A total of 286 publications were identified from the initial database search, and 12 studies, including five RCTs and seven observational cohort studies with a total of 12,682 patients, were included. Significant early survival benefits were observed in patients receiving prehospital TXA compared to those not receiving prehospital treatment. Compared to the control group, the prehospital TXA group exhibited a significant reduction in 24-h mortality with an OR of 0.72 and a 95% CI of 0.54-0.94 (p = 0.02), while no statistically significant difference in the incidence of venous thromboembolism (VTE; OR: 1.14, 95% CI: 0.98-1.33, p = 0.09). No significant differences were observed in other outcomes, such as 28-30-day mortality, overall mortality, length of hospital stay, and the incidence of multiple organ failure (all p > 0.05).

Prehospital TXA decreases early (24-h) mortality in trauma patients without a significant increase in the risk of VTE and other complications, and further studies are still needed to improve and optimize its management strategy.

https://www.crd.york.ac.uk/PROSPERO/, Identifier: CRD 42019132189.

Traumatic brain injury is a leading cause of death and disability. Tranexamic acid, an antifibrinolytic agent, holds the potential for managing intracranial hemorrhages secondary to traumatic brain injury. However, its efficacy and safety remain subjects of ongoing debate.

To better clarify the efficacy and safety of tranexamic acid in that context and to evaluate the need for further studies.

We conducted a comprehensive search of seven electronic databases, eight study repositories, and tertiary sources between January 2021 and 2022 for randomized controlled trials involving victims of traumatic brain injury aged 15 or older who received tranexamic acid versus placebo or standard care. The primary outcomes were all-cause mortality and hemorrhagic complications during treatment. This review incorporated elements of PRISMA guidelines, Cochrane's Risk of Bias assessment, and GRADE to assess evidence quality. Sensitivity analyses were also conducted.

Out of 6,958 references retrieved, 14 of the 17 randomized controlled trials were analyzed, encompassing a total of 15,017 patients. Analyses for all-cause mortality did not reach statistical significance (RR= 0.95, 95%CI= 0.88-1.02 | trial sequential analysis RR= 0.95, 95%CI= 0.87-1.03). However, the analysis of hemorrhagic complications during treatment showed statistical significance for progressive intracranial hemorrhage (RR= 0.82, 95%CI= 0.68-0.99 | trial sequential analysis RR= 0.82, 95%CI= 0.38-1.78). Analyses of secondary outcomes, namely unfavorable neurological outcome and other adverse effects, did not demonstrate statistical significance.

Tranexamic acid use did not demonstrate efficacy based on all-cause mortality but showed a favorable safety profile. Additional clinical trials may shed light on remaining clinical uncertainties. Prospero database registration: CRD42021221949.

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.

Until the beginning of the century, bleeding management was similar in elective surgeries or exsanguination scenarios: clotting tests were used to guide blood product orders and, while awaiting these results, an aggressive resuscitation with crystalloids was recommended. The high mortality rate in severe hemorrhages managed with this strategy endorsed the need for a special resuscitation plan. As a result, modifications were recommended to develop a new clinical approach to these patients, called "Damage Control Resuscitation". This strategy includes four principles: damage control surgery, minimization of crystalloids, permissive hypotension and hemostatic resuscitation. The latter involves the use of antifibrinolytics, correction of preconditions of hemostasis (calcium, pH and temperature) and the early and rapid restoration of intravascular volume with blood products. To enable timely availability and transfusion of blood products, specific actions in different hospital areas need to be synchronized, which are usually organized through Massive Transfusion Protocols or, as they have recently been rebranded, Major Hemorrhage Protocols (MHPs). Although these bundles of actions represent a paradigm change, essential aspects such as their historical evolution, theoretical foundations, terminology and operational elements have yet to be well explored. Considering the wide application range of these tools (emergency departments, interventional radiology, operating rooms and military fields), it is essential to integrate all professionals involved with severe hemorrhage scenarios in the implementation of the aforementioned protocols, from conception to execution and management. This review paper addresses MHP aspects relevant to anesthesiologists, transfusion services and other areas involved with the care of patients with severe bleeding.

With an increase in number of patients on antithrombotic therapies, management of bleeding during dermatologic surgery is increasingly important. As described in Part 1, perioperative discontinuation of antithrombotic therapies may increase the risk of embolic events thus the risks and benefits must be weighed carefully when deciding whether to continue or suspend therapy. However, continuing oral anticoagulants may result in increased intraoperative and postoperative bleeding. Here we describe various methods to effectively achieve hemostasis which include (1) mechanical methods to compress the vasculature, (2) pharmacologic agents that induce vasoconstriction, (3) physiologic agents that augment clot formation, and (4) physical agents that promote platelet aggregation.

The lysine analog tranexamic acid (TXA) is used as a blood protective drug in cardiac surgery, but efficacy and safety outcomes in patients treated with extracorporeal membrane oxygenation (ECMO) after surgery remain poorly understood.

From January 1, 2017 to December 31, 2022, we retrospectively analyzed patients assisted by ECMO after cardiac surgery and divided them into TXA and control groups depending on whether TXA was used or not. The primary study outcome was red blood cell (RBC) transfusion during ECMO.

In total, 321 patients treated with ECMO after cardiac surgery were assessed; 185 patients were eligible for inclusion into to the TXA-intervention group and 136 into to the control group. RBC transfusion during ECMO was 8.0 IU (4.0 IU-14.0 IU) in the TXA group versus 10.0 IU (6.0 IU-16.0 IU) in the control group (p = .034). Median total chest drainage volume after surgery was 1460.0 mL (650.0-2910.0 mL) and 1680.0 mL (900.0-3340.0 mL) in TXA and control groups, respectively (p = .021). Postoperative serum D-dimer levels were significantly lower in the TXA group when compared with the control group; 1.125 µg/mL (0.515-2.176 µg/mL) versus 3.000 µg/mL (1.269-5.862 µg/mL), p < .001. Serious adverse events, including vascular occlusive events, did not differ meaningfully between groups.

In patients treated with ECMO after cardiac surgery, TXA infusion modestly but significantly reduced RBC transfusions and chest tube output when compared with the control group.

The use of tranexamic acid (TXA) has been shown to be effective in reducing haemorrhage and mortality in numerous surgical settings. However, its use in plastic surgery has been limited due to misconceptions related to increased thrombotic events in microsurgery.

We performed a retrospective single-centre cohort study including any patients who underwent autologous free flap tissue transfer at Lister Hospital, Stevenage, from 1 January 2016-20 April 2022. The Chi-squared test was used to determine if there were any significant differences between the proportion of patients who developed any evidence of microvascular thrombosis, flap failure, or return to theatre, and univariate logistic regression was used to calculate odds ratio.

The treatment group (N = 160) received TXA (1 g intravenous) at the time of general anaesthetic induction as per the senior author's routine practice, while the control group (N = 80) did not receive TXA at any point of the hospital admission, according to the normal practice of other surgeons. No differences were found between the proportion of patients who developed microvascular thrombotic complications between the TXA and control group, contributing evidence that TXA is safe to use in microvascular surgery.

TXA may have a role in improving outcomes in plastic surgery procedures by reducing the need for blood transfusions and through anti-inflammatory effects. Our study shows that TXA administration did not increase microvascular thrombosis in free flap reconstructive surgery, contributing evidence that TXA is safe to use in microvascular surgery, however further larger studies are required to improve the power of this study.

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.

The plasma protein fibrinogen is critical for haemostasis and wound healing, serving as the structural foundation of the blood clot. Through a complex interaction between coagulation factors, the soluble plasma fibrinogen is converted to insoluble fibrin networks, which form the skeleton of the blood clot, an essential step to limit blood loss after vascular trauma. This review examines the molecular mechanisms by which fibrinogen modulates bleeding, focusing on its interactions with other proteins that maintain fibrin network stability and prevent premature breakdown. Moreover, we also cover the role of fibrinogen in ensuring clot stability through the physiological interaction with platelets. We address the therapeutic applications of fibrinogen across various clinical contexts, including trauma-induced coagulopathy, postpartum haemorrhage, and cardiac surgery. Importantly, a full understanding of protein function will allow the development of new therapeutics to limit blood loss following vascular trauma, which remains a key cause of mortality worldwide. While current management strategies help with blood loss following vascular injury, they are far from perfect and future research should prioritise refining fibrinogen replacement strategies and developing novel agents to stabilise the fibrin network. Exploiting fibrinogen's molecular properties holds significant potential for improving outcomes in trauma care, surgical interventions and obstetric haemorrhage.

Resuscitation with cold-stored whole blood (WB) has outcome benefits, but benefits varied by patient sex is unknown. There are also concerns about alloimmunization risk for premenopausal females given WB, leading to some protocols excluding this cohort. We sought to analyze WB utilization, outcomes, and disparities by patient sex.

This is a secondary analysis of a prospective multicenter study of WB resuscitation. Patients were stratified by sex and compared by transfusion strategy of WB or component therapy (CT). Generalized estimated equation models using inverse probability of treatment weighting were utilized.

There were 1,617 patients (83% male; 17% female) included. Females were less likely to receive WB versus males (55% vs. 76%; p < 0.001), with wide variability between individual centers (0%-33% female vs. 66%-100% male, p < 0.01). Male WB had more blunt trauma (45% vs. 31%) and higher shock index (1.0 vs. 0.8) compared with the male CT cohort (all p < 0.05) but similar Injury Severity Score. The female WB cohort was older (53 vs. 36) and primarily blunt trauma (77% vs. 62%) compared with the female CT cohort (all p < 0.05) but had similar shock index and Injury Severity Score. Male WB had lower early and overall mortality (27% vs. 42%), but a higher rate of acute kidney injury (16% vs. 6%) vs. the male CT cohort (all p < 0.01). Female cohorts had no difference in mortality, but the WB cohort had higher bleeding complications. Whole blood use was independently associated with decreased mortality (OR, 0.6; p < 0.01) for males but not for females (OR, 0.9; p = 0.78).

Whole blood was independently associated with a decreased mortality for males with no difference identified for females. Whole blood was significantly less utilized in females and showed wide variability between centers. Further study of the impact of patient sex on outcomes with WB and WB utilization is needed.

Prognostic and Epidemiological; Level IV.

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.