Hemorrhage

Trauma causes at least 5.8 million deaths worldwide annually, accounting for 1 in 10 of all global deaths. Uncontrolled bleeding within 24 hours after trauma is the leading cause of death in trauma patients, and about one-third of patients present with trauma-induced coagulopathy on admission. Fatal severe traumatic hemorrhage is the most common preventable factor contributing to death. Tranexamic acid (TXA), a synthetic lysine derivative, competitively inhibits plasminogen activation, preventing fibrin clot breakdown and thereby enhancing hemostasis and reducing blood loss. Randomized controlled trials such as CRASH-2 have confirmed that TXA significantly reduces mortality in patients with severe traumatic bleeding. TXA has therefore become a cornerstone of traumatic hemorrhage treatment, with current international guidelines recommending 1 g intravenous bolus (over \>10 minutes) plus 1 g intravenous maintenance infusion (over 8 hours). However, severe traumatic hemorrhage is typically managed in high-pressure, chaotic battlefield or emergency settings, where this complex, time-sensitive, multi-step divided regimen is difficult to fully execute in real-world practice. The omission rate of the second maintenance infusion is particularly high, reaching up to 67% during prehospital-to-hospital handover. Rowell et al. showed that even with a strict research protocol, completion of the planned 8-hour in-hospital maintenance infusion was only about 70%. Previous pharmacokinetic studies found that without the second maintenance dose, 21% of patients receiving an initial 1 g dose had already failed to achieve effective plasma concentrations at hospital admission (approximately 1.5 hours post-dose). Thus, the inherent difficulty of fully executing the divided regimen may prevent patients from receiving the full benefits of TXA. To address this, a simplified regimen of a single 2 g loading dose without maintenance infusion has been recommended in recent expert consensus statements, especially for prehospital or battlefield settings. However, these recommendations were mainly based on the 2020 Rowell et al. randomized controlled study, whose exploratory analysis suggested potential mortality reduction with the simplified regimen. That study enrolled patients with traumatic brain injury and had limited statistical power, so evidence on the efficacy and safety of the simplified regimen in patients with severe traumatic hemorrhage remains lacking. Based on the pharmacokinetic study by Grassin-Delyle et al., a single 2 g loading dose is hypothesized to maintain effective concentrations during the peak fibrinolytic period (within 3 hours post-injury), while the transient peak plasma concentration remains well below the toxicity threshold of 500 μg/mL. We therefore hypothesize that, in patients with severe traumatic hemorrhage, the simplified TXA regimen is non-inferior to the divided regimen in efficacy, including bleeding control. However, the primary limitation of a large randomized controlled trial to verify this hypothesis is that safety concerns regarding the simplified regimen due to higher transient plasma concentrations compared with the divided regimen have not been clearly resolved. Previous systematic reviews concluded that safety events such as thrombosis and seizures are dose-dependent, and that a total daily dose not exceeding 2 g is safe. Previous pharmacokinetic studies also suggest that the transient peak concentration of the simplified regimen should be well below the toxicity threshold. Although expert consensus has recommended the simplified regimen, suggesting it can be considered safe, studies directly comparing the two regimens are lacking, particularly regarding whether the simplified regimen increases safety risks when the total dose is identical. Before conducting a larger, more definitive efficacy trial, it is also important to evaluate recruitment rates, protocol adherence, accurate sample size estimation, and other potential barriers. For these reasons, we designed this pilot study, primarily to evaluate the safety of the simplified TXA regimen compared with the divided regimen in patients with traumatic hemorrhagic shock, and the feasibility of a subsequent randomized controlled trial.

Severe traumatic injury involving multiple body regions (polytrauma) carries a high risk of rapid bleeding, tissue hypoperfusion, and circulatory collapse. In the emergency setting, standard vital signs such as blood pressure and heart rate alone may not detect impending circulatory failure until significant deterioration has already occurred. The purpose of this prospective observational cohort study is to develop and internally validate a bedside clinical prediction model that identifies adult polytrauma patients at risk of early hemodynamic deterioration within 24 hours of arrival at the Emergency Department of Assiut University Hospital. Eligible adult patients presenting with acute trauma across at least two major body regions within 6 hours of injury will receive standard clinical evaluation and trauma resuscitation. Alongside routine care, researchers will record baseline predictor variables during initial evaluation, including: * Shock Index, calculated from heart rate and systolic blood pressure. * Inferior vena cava (IVC) respiratory collapsibility assessed via non-invasive bedside point-of-care ultrasound. * Initial blood gas and biochemical markers, including blood lactate concentration and base deficit. * Baseline neurological status using the Glasgow Coma Scale (GCS) and patient age. Participants will be followed for 24 hours to monitor for hemodynamic deterioration, defined as persistent or recurrent hypotension, the need for vasopressor or inotropic medications, major blood transfusion (at least 4 units of packed red blood cells), emergency surgical or interventional procedures to control bleeding, or trauma-related circulatory collapse death. The gathered data will be analyzed according to TRIPOD guidelines to create a multimodal risk tool that can assist emergency clinicians in recognizing high-risk trauma patients early.

The CAlcium and VAsopressin following Injury Early Resuscitation (CAVALIER) Trial is a proposed 4 year, double-blind, mutli-center, prehospital and early in hospital phase randomized trial designed to determine the efficacy and safety of prehospital calcium and early in hospital vasopressin in patients at risk of hemorrhagic shock.

The purpose of this study is to evaluate the safety and effectiveness of Onyx™ LES in the treatment of subjects with active arterial bleeding in the peripheral vasculature outside of the heart and brain.

Clinically, DSA-VDet can continuously indicate suspected bleeding regions throughout a complete angiographic sequence and provide a second-reader opinion to the operator. It is expected to reduce the time required for frame-by-frame review and localization of culprit vessels, reduce missed detection of small, multiple, or unusually located bleeding sites, and improve consistency among physicians with different levels of experience. Faster culprit-vessel localization may also reduce repeat angiography, radiation exposure, and unnecessary superselective catheterization. These potential benefits will be tested in the prospective randomized trial; the study does not assume that the model will necessarily improve clinical outcomes. From a translational perspective, the study will establish a standardized temporal DSA database spanning multiple centers, devices, and anatomical regions, together with bleeding-site annotation standards, a model suitable for real-time deployment, and a pathway for clinical evaluation. These resources may provide a reproducible technical foundation for regional collaboration in emergency interventional care and AI-assisted interpretation in lower-resource hospitals. The core value of this study is therefore to address the 'single-region, weak-temporal, algorithm-centered, clinically under-evaluated' limitations of existing models. Using multicenter DSA videos from multiple anatomical regions, the study will leverage contrast kinetics and motion information to improve detection of small bleeding sites and will progress from retrospective validation through controlled physician interpretation to a prospective randomized trial, providing a continuous evaluation from technical performance to clinical benefit.

This is a multicentre, prospective, three-arm, parallel-group randomized controlled superiority trial evaluating fibrillar Type-I collagen haemostat (Hemocoll®) FTC, Avitene™ Microfibrillar Collagen Hemostat (MCH), and conventional bone wax for control of bleeding from exposed cancellous bone following planned single-ray amputation. Adults undergoing single-ray amputation involving a phalanx, metacarpal or metatarsal will be randomized in a 1:1:1 ratio. The primary comparison is Hemocoll® FTC versus Avitene™ MCH. Complete haemostasis is defined as VIBe Grade 0 sustained continuously for 60 seconds without rescue haemostasis at the prespecified anatomical assessment time: 2 minutes for phalanx, 3 minutes for metacarpal, and 5 minutes for metatarsal. Secondary comparisons include Hemocoll® FTC versus bone wax and Avitene™ MCH versus bone wax.

This observational study will collect information from adult patients in Japan who are treated with Histoacryl® to stop bleeding from arteries in the chest or abdomen, in order to better understand how well the treatment works and how safe it is during routine medical care.

The goal of this clinical trial is to compare two strategies for closing the main artery access site in adult patients undergoing transcatheter aortic valve implantation (TAVI) through a blood vessel in the leg (transfemoral access). The main questions it aims to answer are: Does using a single suture device lower the rate of access-related vascular complications compared to using a hybrid combination of a suture device and a plug-based closure device? How do the two closure strategies compare regarding bleeding complications, procedure time, and time to complete vessel sealing? Researchers will compare a single-suture closure strategy to a hybrid closure strategy (one suture plus one plug-based device) to see if using a single suture reduces vessel-related complications and improves patient safety after TAVI. Participants will: Undergo standard pre-procedure screening and TAVI via the main artery in the leg as part of routine medical care. Receive an initial single-suture placement before the large TAVI delivery system is inserted. Be evaluated after sheath removal for initial bleeding control; qualifying participants will then be randomly assigned (1:1) to either receive no additional device (single suture group) or receive a plug-based closure device (hybrid group). Have their heart and access site monitored during hospitalization, including laboratory checks and imaging prior to discharge. Complete a 72-hour safety and complication evaluation.

The purpose of this clinical study is to assess the efficacy and safety of TachoSil compared to the widely known and used for \> 60 years local hemostatic product Surgicel Original as an adjunct to control mild to moderate soft tissue bleeding during surgery.

In severe lung or heart disease, ExtraCorporeal Membrane Oxygenation (ECMO) may be used temporarily and can be responsible for major haemorrhagic complications. Thrombocytopenia and possibly thrombopathy promote bleeding. The primary objective is to characterize platelet dysfunction by aggregometry tests over time. Secondarily, investigators seek a correlation between haemorrhagic complications at day 10 and markers of platelet action and dysfunction; also, with the level of anticoagulation and inflammation by biomarkers.

MSU-ICH is a prospective, multicenter, Week-wise-randomized, open-label, blinded-endpoint (PROBE) clinical trial comparing ultra-early prehospital blood pressure lowering delivered by a Mobile Stroke Unit (MSU) with standard Emergency Medical Services (EMS) in patients with spontaneous intracerebral hemorrhage.

The objective of this multicenter, single-arm, observational study is to determine the feasibility and effectiveness of early administration of FDA-approved, pre-thawed Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) in trauma patients with hemorrhagic shock (HS) and functional hypofibrinogenemia. This study will determine whether rapid point-of-care testing for functional hypofibrinogenemia and availability of a shelf-stable fibrinogen complex (IFC) results in shorter time to administration of fibrinogen replacement and correction of functional hypofibrinogenemia, as compared with historical controls and published literature using conventional cryoprecipitate-AHF (CRYO-AHF). This study aims to: * Demonstrate the feasibility and response to early administration of pre-thawed IFC when ordered during initial resuscitation of severely injured patients with HS and functional hypofibrinogenemia. * Assess the effectiveness of early administration of pre-thawed IFC on correction of functional hypofibrinogenemia and on proximate process measures of resuscitation, including time to hemostasis, time to completion of resuscitation, and total volume of resuscitation. * Assess clinical outcomes in severely injured patients with HS and functional hypofibrinogenemia receiving early administration of pre-thawed IFC.

Although procedural abortion in the second trimester is extremely safe, hemorrhage is one of the leading causes of morbidity and mortality. Tranexamic acid (TXA) is used commonly in obstetrics to prevent or manage intrapartum or postpartum hemorrhage and has been associated with decreased mortality and decreased blood loss at the time of birth. Some guidelines are recommending the use of TXA for both the prevention and management of bleeding for abortion care. However, there are currently no published studies assessing the association between TXA and bleeding outcomes for abortion procedures. This study will involve a randomized, placebo-controlled trial of pregnant patients aged 18 and older desiring dilation and evacuation (D\&E) for abortion or fetal demise at 18-24 weeks gestation. The primary aim is to determine whether prophylactic TXA has an effect on the need for additional interventions to control bleeding at the time of D\&E. The secondary aim is to determine whether prophylactic TXA has an effect on the mean quantitative procedural blood loss.

Atrial fibrillation (AF) is the most common arrhythmia, significantly increasing the risk of stroke, heart failure, hospitalization and death in patients. Studies have shown that standardized anticoagulation can effectively reduce the risk of stroke by 64% and the risk of death by 26% in AF patients. Therefore, both European and American guidelines recommend standardized oral anticoagulation (OAC) as an important treatment strategy for stroke prevention in AF patients. However, the use of OAC may also increase the risk of bleeding in patients. Results from large AF anticoagulation randomized trials show that the annual risk of anticoagulation-related bleeding mortality is 2% to 3%. Therefore, according to the guidelines recommendations, assessing the bleeding risk is necessary in patients with anticoagulant indications. Percutaneous left atrial appendage occlusion (LAAO) is a device-based therapy that aims to prevent ischemic stroke in patients with AF. For patients with contraindications to long-term anticoagulation therapy, LAAO can be considered as an alternative strategy to oral anticoagulation (Class II B recommendation) to prevent ischemic stroke and thromboembolism. Multiple studies have shown that LAAO is non-inferior to warfarin and novel oral anticoagulants in stroke prevention for non-valvular AF patients. Age is not only a risk factor for stroke but also an important risk factor for bleeding. In the elderly population, especially those with frailty, the risk factors for both stroke and bleeding are often increased. Currently, there is insufficient evidence to support the use of OAC in frail elderly patients with relative anticoagulant contraindications. Therefore, elderly AF patients may be one of the potential beneficiary groups for LAAO. However, most previous clinical studies on LAAO were based on small sample sizes to analyze their safety and efficacy, and clinical data on the safety and efficacy of LAAO in this high-risk population of elderly AF patients are still limited. To address this, the study aims to conduct a multicenter randomized controlled trial to compare the efficacy and safety of catheter ablation combined with LAAO versus catheter ablation combined with OAC in elderly AF patients with high bleeding risk, filling the gap in this research area. To address these limitations, this multicenter randomized controlled trial is designed to evaluate the efficacy and safety of catheter ablation combined with LAAO versus catheter ablation combined with OAC in elderly AF patients at high risk for bleeding. The primary objective of the study is to compare the 12-month incidence and time-to-occurrence of the composite clinical endpoint. This endpoint includes stroke/TIA, systemic embolism, ISTH-defined major bleeding. By establishing these metrics within the first year, the study aims to fill the current void in clinical evidence and provide a standardized treatment strategy for high-risk elderly patients. In addition to the primary endpoints, the study will conduct a comprehensive long-term evaluation extending to 24 months post-procedure to assess the durability of both treatment strategies. Secondary objectives include the assessment of perioperative safety, specifically focusing on serious intraoperative complications and major adverse events occurring within the first seven days after the LAAO procedure. The trial will also measure long-term rhythm control by tracking the rate of freedom from AF recurrence at the one-year and two-year marks. Furthermore, the study seeks to verify the hypothesized superiority of the ablation-plus-LAAO strategy in reducing the specific burden of anticoagulation-related major bleeding and stroke. Beyond clinical safety and efficacy, the trial will analyze the practical aspects of the two interventions, including procedural success rates, operation duration, fluoroscopy time, and the total duration of hospitalization. A critical component of the research involves identifying specific risk factors associated with complications, with a specialized focus on how frailty scores influence procedural tolerance and long-term prognosis. The study will further explore how different types of AF respond to the LAAO strategy and assess the impact of each treatment on non-major bleeding events. Ultimately, the trial aims to determine which strategy offers a superior improvement in the overall quality of life for elderly patients, thereby optimizing future clinical guidelines.

This is a prospective, non-randomized, observational cohort study conducted at the FSBI "NMRC TPM" of the Ministry of Healthcare of the Russian Federation. Left atrial appendage closure (LAAC) has been shown to be non-inferior to oral anticoagulation for preventing cardioembolic events in patients with atrial fibrillation. However, the optimal post-procedural antithrombotic regimen following LAAC remains unclear, with no consensus on evidence-based therapy. Given current trends in cardiology favoring reduced-intensity antithrombotic strategies, this study aims to contribute to the evidence base by evaluating whether LAAC followed by reduced-dose apixaban (2.5 mg BID) for 3 months with subsequent complete withdrawal of antithrombotic therapy is superior to long-term standard-dose DOAC therapy in patients with non-valvular atrial fibrillation.

The goal of this trial is to determine if postpartum blood loss can be reduced by replenishing coagulation factor XIII (FXIII) at an early stage of postpartum hemorrhage (PPH). Summary of current body of evidence: * Morbidity and mortality due to PPH is rising. * Current guidelines focus on replenishment of fibrinogen as an initial step in the treatment of PPH-related coagulopathy, despite non-conclusive evidence in all prospective trials. * Trials from other specialties demonstrate a significant impact of FXIII on perioperative bleeding complications; a previous study at the University Hospital Zurich showed that pre-partum factor XIII activity had a strong association to postpartum blood loss. Therefore, this nationwide, multi-center, randomized, controlled trial in multiple perinatal centers across Switzerland will be conducted. The goal is to determine if postpartum blood loss and PPH-related complications can be reduced by replenishing FXIII. All participating women receive, according to the national guideline, 1g tranexamic acid (TXA) i.v. in case of PPH (measured blood loss \[MBL\] ≥ 500 mL) during the pre-study phase. Randomization takes place if bleeding continues and exceeds 700mL. The intervention group then receives FXIII (Fibrogammin®) according to approved dosage in addition to obstetric standard of care treatment for causes of PPH; the control group receives only standard of care treatment.

This pilot study aims to assess performance, safety and feasibility of U-CaVIT method (Uro-Catheter Vacuum Induced Tamponade), using the Rüsch® Brillant Silicone Balloon Catheter, an urological catheter, for the prevention of atonic PPH in high-risk women undergoing cesarean delivery. The U-CaVIT method has been implemented at the Department of Obstetrics at university hospital of Zurich (USZ) due to temporary supply issues with the Bakri® Balloon Catheter. The Rüsch® Balloon Catheter is used in case of uterine atony when standard first-line uterotonic treatments have failed or in some cases as add-on therapy in non-atonic PPH. In the meantime, the use of U-CaVIT has become standard practice at the USZ for the treatment of atonic PPH, appearing to be user-friendly, clinically effective according to treating physicians, well tolerated by the treated women and cost-saving compared to the previously used Bakri® Balloon.

This study uses frequency domain near-infrared spectroscopy coupled with diffuse correlation spectroscopy (FDNIRS-DCS) technology for monitoring cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO2) at the bedside for newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) and/or post-hemorrhagic hydrocephalus (PHH) in comparison to newborns with hydrocephalus of a different etiology (VC) and healthy controls (HC). We hypothesize that baseline cerebral metabolic dysfunction is a better biomarker for GM-IVH and PHH severity and response to PHH treatment. This is a Boston Children's Hospital (BCH)-institutional review board(IRB) approved, multi-site study that includes collaboration with Brigham and Women's Hospital (BWH) and Beth Israel Deaconess Medical Center (BIDMC). Pei-Yi Lin receives funding from The National Institute of Health (NIH) to support the study and is the overall principal Investigator (PI) overseeing the study.

Project Name: Randomized Controlled Clinical Study on oral hygiene and prophylactic antibiotics to prevent Intracerebral Hemorrhage associated pneumonia Research Objectives: To evaluate the effectiveness, safety and health economics value of enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia. 1. To clarify the effectiveness of enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia. 2. To clarify the safety of enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia. 3. To clarify the health economics value of low-intensity enhanced oral hygiene combined with antibiotics in preventing post-cerebral hemorrhage pneumonia. Research Design: Research Type: Multicenter, Randomized, Controlled, Open Label, Blinded Endpoint Research Design Research Hypothesis: Intensive oral hygiene combined with antibiotic treatment is beneficial in reducing the incidence of pulmonary infections related to cerebral hemorrhage.

Trauma is the leading cause of death and disability in children in the United States. The objective of this study is to evaluate the benefits and harms of tranexamic acid (TXA; a drug that stops bleeding) in severely injured children with hemorrhagic brain and/or torso injuries. Using thromboelastography, we will measure baseline fibrinolysis to assess for treatment effects of TXA at different levels of fibrinolysis.

Hemodynamic evaluation during pediatric anesthesia is essential to care management. Intraoperative cardiovascular instability is frequent in major surgeries, and appropriate monitoring is necessary to ensure safe anesthetic conduction and promptly detect changes in blood pressure, cardiac output, blood volume, and organ perfusion. In this context, advanced hemodynamic monitoring, continuous measuring, and estimating various parameters can allow a more specific hemodynamic profile and help identify the causal mechanisms of its variability. Moreover, the reference ranges of hemodynamic values in different pediatric ages and how to best monitor hemodynamic status in pediatrics are still debated. Surgical treatment of craniosynostosis is usually performed at an early age, between 3 and 8 months of age. The operation is burdened by a high risk of hemodynamic instability related mainly, but not only, to potential substantial hemorrhagic losses. This study aims to characterize the hemodynamic events occurring during corrective craniosynostosis surgery, recorded simultaneously with standard monitoring and Pressure Recording Analytic Method (PRAM), and to analyze the paired measurements.

This single-center, prospective, randomized controlled trial was approved by the institutional ethics committee and overseen by an independent data and safety monitoring board. It enrolled patients with hemorrhagic shock caused by trauma or major gastrointestinal bleeding. Using a random-number-table method, participants were allocated to three groups: (1) Control group: standard massive transfusion protocol (MTP) with transfusing type-specific blood components in a 1:1:1 ratio. (2) Type-specific whole-blood group: following emergency ABO typing and cross-matching, type-specific whole blood was transfused. (3) Low-titer group O whole-blood group: in the emergency phase, 4 units of low-titer group O whole blood (anti-A/B IgM titer \< 1:64) were infused; after definitive ABO typing, patients were switched to type-specific whole blood. Clinical data were automatically extracted from the electronic medical record system. Primary endpoints were efficacy (28-day survival), timeliness (transfusion waiting time and time to achieve target mean arterial pressure), cost-effectiveness (total blood consumption and transfusion-related expenses), and safety (transfusion-associated adverse events including TRALI and hemolytic reactions).Statistical analyses included Kaplan-Meier survival curves and Cox proportional-hazards regression, adjusting for confounders such as age and disease severity scores. The advantages and disadvantages of each transfusion strategy were evaluated, and an optimized strategy for emergency blood transfusion in hemorrhagic shock was developed. This strategy was peer-reviewed and refined, culminating in a standardized, multidisciplinary, emergency-transfusion protocol.

Evaluate the effectiveness of the Q Therapeutic (BQ 3.0) System for individuals with chronic stroke in improving upper extremity function as determined by change in functional outcome measures after 3-month treatment, including in-clinic and at-home sessions.

The goal of this clinical trial is to learn if tranexamic acid (TXA) helps reduce bleeding during bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG) and mini gastric bypass (MGB). It will also look at how safe TXA is for people undergoing these procedures. The main questions it aims to answer are: Does TXA reduce the amount of blood loss during bariatric surgery? Are there any side effects or complications in patients who receive TXA? Researchers will compare TXA to standard care (no TXA) to see if it is effective in reducing bleeding. Participants will: Receive either TXA or no TXA (placebo) before surgery Undergo standard bariatric surgery (LSG or MGB) Have their blood loss, hemoglobin levels, and any complications monitored during and after surgery

The purpose of this study is to assess the effectiveness of prophylactic oxytocin on hemorrhage rates for second trimester dilation and evacuation (D\&E) in the clinic setting.