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Background: Tourniquets are widely used in limb fracture surgeries. Controversies still exist about the pressure inflated, including unified tourniquet inflation pressure (UTIP) and personalized tourniquet inflation pressure (PTIP). This study evaluated the hemostatic effect between UTIP and PTIP based on systolic blood pressure (SBP) in extremity fracture patients. Materials and methods: Patients with fresh extremity fractures requiring tourniquets during surgeries were prospectively enrolled and randomly assigned to the UTIP and PTIP groups. The inflation pressure was set to 250 mmHg for the upper extremities and 300 mmHg for the lower extremities in the UTIP group and SBP plus 50 mmHg for the upper extremities and SBP plus 100 mmHg for the lower extremities in the PTIP group. The primary outcome was a hemostatic effect evaluated by the surgeon (satisfied or dissatisfied). Other secondary outcomes included postoperative changes in limb swelling and tourniquet-related complications. Results: A total of 144 patients were enrolled and randomly assigned to the UTIP group or the PTIP group, and each group has 72 patients (36 upper limb and 36 lower limb). Totally, the hemostasis effect of the PTIP group was worse than that of the UTIP group by non-inferiority test. The hemostatic effect of upper limb fractures with SBP plus 50 mmHg for tourniquet inflation pressure was also worse than that with 250mmHg; however, there was no statistically significant difference between 300mmHg and SBP plus 100 mmHg in the lower limb group hemostasis effect due to a lack of power. Also, no difference was observed in the incidence of complications (p = 1.000) and postoperative changes in limb swelling during 2 days after surgery (upper limb: P1 = 0.546, P2 = 0.545; lower limb: P1 = 0.408, P2 = 0.857) between the PTIP and UTIP group. Conclusion: In the surgery of limb fractures, setting SBP + 50mmHg as tourniquet pressure may not be sufficient for upper limbs. Also, we found no difference between the SBP + 100mmHg and the unified 300mmHg for lower limb surgeries. [ABSTRACT FROM AUTHOR]

It has been recognized that shortened activated partial thromboplastin time (aPTT) may be caused by various preanalytical conditions. As coagulation Factor VIII is included in the in vitro intrinsic coagulation cascade measured by aPTT, we hypothesized that the shortened aPTT could be a result of elevated FVIII activity. We aimed to inspect the connection of elevated FVIII with shortened aPTT, and the possible effect inflammation has on routine laboratory parameters. 40 patients from various hospital departments with aPTT measurement below the lower limit of the reference interval (<23.0 s) were included in the study. To compare the obtained results with aPTT measurements in the non-inflammatory state, samples from 25 volunteers (laboratory personnel) were collected. White blood cell count, C-reactive protein, aPTT, and FVIII values were measured in the control group. Only two samples among 40 patients with shortened aPTT (5 %) were clotted. Out of the remaining 38, 26 had FVIII activity above 150 % (upper limit of a reference interval), median value of 194 % (IQR: 143–243 %). Seven samples in the control group had shortened aPTT results (36 %). However, all coagulation samples were clot and hemolysis-free. Multiple regression identified only FVIII activity as an independent variable in predicting aPTT values (p=0.001). Our results support the thesis that shortened aPTT is rarely a consequence of preanalytical problems. Elevated FVIII activity causes shortened aPTT, not only in the inflammatory state but also in individuals with concentration of inflammatory markers within reference intervals. [ABSTRACT FROM AUTHOR]

We present a case of a child with a suprasellar arachnoid cyst and hydrocephalus who developed a massive traumatic epidural hematoma following a fall. This represents the first reported case of such a condition. The case is characterized by a progressive increase in hemorrhage leading to a massive hematoma, yet with relatively mild clinical symptoms. The hemorrhage originated from extensive blood seepage from the dura mater. Intraoperative hemostasis was challenging, and there was a large residual cavity of the epidural hematoma without repositioning of brain tissue after removal of the hematoma. Surgical measures such as extensive continuous compression hemostasis with Surgicel, the half-suspension technique, and continuous external drainage were employed to address these challenges. A second-stage surgery for the treatment of the suprasellar arachnoid cyst was performed 1.5 months after hematoma evacuation, utilizing neuroendoscopic ventriculocisternostomy (VCC). We recommend that for patients with traumatic brain injury and hydrocephalus, especially those with skull fractures or minimal intracranial hemorrhage, relying solely on clinical symptom observation and monitoring is insufficient. Timely and close monitoring with cranial CT is crucial for the early detection of progressive intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

The in-situ activation of adaptive immunity at the surgical site has demonstrated remarkable efficacy in inhibiting various forms of tumour recurrence and even holds the promise of a potential cure. However, extensive research and bioinformatic analysis conducted in this study have unveiled the formidable challenge posed by melanoma-intrinsic β-catenin signaling, which hinders the infiltration of cytotoxic T-lymphocytes (CTLs) and their subsequent anti-tumour action. To overcome this obstacle, a β-catenin antagonist called carnosic acid (CA) was co-assembled with a RADA-rich peptide to create a nanonet-derived hydrogel known as Supra-gelδCA. This injectable hydrogel is designed to be retained at the surgical site while simultaneously promoting hemostasis. Importantly, Supra-gelδCA directly releases CA to the site of residual tumour lesions, thereby enhancing infiltration of CTLs and subsequently activating adaptive immunity. Consequently, it effectively suppresses postoperative recurrence of skin cutaneous melanoma (SKCM) in vivo. Collectively, the presented Supra-gelδCA not only provides an efficacious immunotherapy strategy for regulating adaptive immunity by overcoming the obstacle posed by melanoma-intrinsic β-catenin signaling-induced absence of CTLs but also offers a clinically translatable hydrogel that revolutionizes post-surgical management of SKCM. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: The aim of this systematic review was to evaluate whether platelet-rich-fibrin (PRF) is effective in preventing postoperative bleeding after dental extractions in patients on anticoagulation or antiplatelet therapy compared to stitches alone and different hemostatic agents. Materials and methods: This systematic review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42024562289). Two authors independently performed searches in several databases, including PubMed, EMBASE, Cochrane Library, and SCOPUS. Results: In total, 789 studies were identified, of which 11 met the inclusion criteria after full-text screening. Four studies evaluated the efficiency of PRF in patients on antiplatelet therapy, and seven studies analyzed its hemostatic effect in patients on anticoagulants. All studies showed sufficient hemostasis when PRF was used, but due to heterogeneity meta-analysis was not possible. Conclusions: Despite the use of different protocols and control groups, PRF treatment seems to be superior to only stitches and inferior to chitosan dressings concerning the time of hemostasis. Additionally, PRF seems to be beneficial in terms of faster wound healing and less postoperative pain. Clinical relevance: PRF is known to enhance soft tissue healing and reduce postoperative pain. As a fully autologous platelet concentrate, it can support hemostasis after dental extractions in patients on antiplatelet or anticoagulation therapy. This systematic review aims to provide an update of the existing literature on PRF and its hemostatic capacity in patients with blood thinning medication. [ABSTRACT FROM AUTHOR]

The aesthetics of the periorbital region are significantly influenced by the position of the eyebrows, forehead wrinkles, and upper eyelid ptosis, with aging-related eyebrow ptosis playing a major role. Brow lift surgery has seen a marked increase in popularity, driven by a variety of techniques tailored to individual patient needs. The 'gliding brow lift' technique, which employs a minimally invasive subcutaneous approach using a hemostatic net, represents a recent advancement in eyebrow rejuvenation. This article outlines our three-year experience and adaptation with this technique, which is divided into three sequential steps: (1) subcutaneous dissection; (2) internal eyebrow fixation; (3) skin redraping. Our modified gliding brow lift technique combines simplicity, minimal equipment requirements, conservative principles that limit scarring and avoid skin resection, and long-lasting results with few complications, making it an attractive option for brow rejuvenation. [ABSTRACT FROM AUTHOR]

[Display omitted] Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization. Microporous GD-BF scaffolds displayed good elastic deformation recovery and promoted neo-tissue formation. The DA could enable thermal crosslinking and enhance the mechanical properties and structural stability of the GD-BF scaffolds. The BGF-mediated release of therapeutic ions shorten hemostatic time (<30 s) in a rat tail amputation model and a rabbit artery injury model alongside inducing the regeneration of skin appendages (e.g., blood vessels, glands, etc.) in a full-thickness excisional defect model in rats (percentage wound closure: GD-BF2, 98 % vs. control group, 83 %) at day 14 in vitro. Taken together, these aerogel scaffolds may have significant promise for soft and hard tissue repair, which may also be worthy for the other related disciplines. [ABSTRACT FROM AUTHOR]

Background Aims Methods Results Conclusions Trauma‐induced coagulopathy (TIC) is associated with negative outcomes. Pediatric TIC has been described most often in older children. Children undergo normal developmental hemostasis, but it is unknown how this process impacts the risk of TIC across childhood.To understand variations in coagulation testing and TIC across pediatric age groups.We evaluated testing patterns of coagulation studies at presentation and over the first 72 h of hospitalization by pediatric age group at a large, Level I trauma center, 2015–2020. The frequency of TIC was determined using published, age‐specific reference ranges and controlling for injury severity. We performed subgroup analyses of those with isolated severe traumatic brain injury (TBI) and those who presented directly from the scene of injury.Data from 2409 pediatric patients were available; 333 patients had isolated severe TBI. Children <1 year were least likely to be tested for TIC at presentation and over the first 72 h, even among the most injured. Fibrinogen testing was uncommon, regardless of injury severity. TIC was common: 22% of patients had TIC at presentation and 35% by 72 h. Greater injury severity was associated with TIC. Children 1–4 and 5–9 years had a higher frequency of TIC at presentation and over 72 h compared to older children in the least injured cohort. We saw no difference in frequency of TIC between age groups in the subset with isolated severe TBI. Using age‐specific criteria, patients most often met TIC criteria by INR/PT, followed by platelet count, and least commonly by aPTT. The presence of TIC was associated with in‐hospital mortality (OR 4.10, 95% CI 2.06–8.17).Significant sampling bias exists in clinical data collection among injured children and adolescents. Contrary to previous reports and using age‐specific TIC criteria, younger children are not at lower risk of TIC than older children when controlling for injury severity. [ABSTRACT FROM AUTHOR]

Background: Hypothermia and acidosis individually inhibit haemostasis. We designed this study with the aim to investigate whether rivaroxaban combined with hypothermia or acidosis exhibit synergistic inhibitory effects on haemostasis using ROTEM®. Methods: Patients with a clinical indication to start rivaroxaban treatment were prospectively included. Blood samples were collected before initiation of treatment and the day after. All blood samples were in vitro modified with respect to temperature (incubated and analysed at 28, 33, 37 and 40 degrees Celsius (°C)) and pH (6.8, 7.0, 7.2 and 7.4). The temperature and acidosis effects on the ROTEM EXTEM variables clotting time (CT), clot formation time (CFT) and alpha-angle (AA) were measured along with the individual effect of rivaroxaban on the same variables. The additive effect was calculated. The observed (potential synergistic) effects for the temperature and pH modified rivaroxaban samples on the same ROTEM variables, were registered. Differences between the additive and observed (potential synergistic) effects were analysed using matched non-parametric hypothesis testing. Results: In total, 13 patients were included. Hypothermia and rivaroxaban exhibited a synergistic effect on CT at 28 °C (p = 0.0002) and at 33 °C (p = 0.0007). The same applied for acidosis at pH 6.8 (p = 0.003) and pH 7.0 (p = 0.003). There were no signs of synergistic effects of rivaroxaban and temperature or acidosis on CFT. In AA there were signs of synergism at 28 °C (p = 0,001), but not at other tested temperatures or pH levels. Conclusions: The combination rivaroxaban together with hypothermia or acidosis demonstrated inhibitory synergistic effects on haemostasis. Trial registration: The study was retrospectively registered 2023-03-01 at ClinTrials.gov with NCT05669313. [ABSTRACT FROM AUTHOR]

A series of new isatin-3-hydrazones bearing different ammonium fragments was synthesized by a simple and easy work-up reaction of Girard's reagents analogs with 1-(3,5-di-tert-butyl-4-hydroxybenzyl)isatin. All derivatives have been shown to have antioxidant properties. In terms of bactericidal activity against gram-positive bacteria, including methicillin-resistant strains of Staphylococcus aureus, the best compounds are 3a, 3e, and 3m, bearing octyl, acetal, and brucine ammonium centers, respectively. In addition, brucine and quinine derivatives 3l, and 3j exhibit platelet antiaggregation activity at the level of acetylsalicylic acid, and this series of isatin derivatives does not adversely affect the hemostasis system as a whole. Thus, all the obtained results can lay the groundwork for future pharmaceutical developments for the creation of effective antibacterial drugs with reduced systemic toxicity due to the presence of antioxidant properties. [ABSTRACT FROM AUTHOR]

Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually "blinded" with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Percutaneous liver biopsy is essential for diagnosing hepatic amyloidosis. Post biopsy hemorrhage is unusual but can occur. The potential for bleeding can result from various factors, such as the deposition of amyloid in the hepatic parenchyma or vessel wall, deficiencies in coagulation factors, hyperfibrinolysis, and platelet dysfunction. Transarterial embolization can be a safe and effective method for achieving hemostasis. [ABSTRACT FROM AUTHOR]

Patients with severe and sometimes moderate hemophilia B are prophylactically treated with factor IX concentrates to prevent bleeding. For some time now, various extended terminal half‐life (EHL) recombinant factor IX concentrates are available allowing less frequent administration during prophylaxis in comparison to standard half‐life recombinant FIX (rFIX). Especially, recombinant FIX‐Fc fusion protein (rFIXFc; Alprolix®) exhibits a rapid distribution phase, potentially due to binding to type IV collagen (Col4) in the extravascular space. Studies suggest that the presence of extravascular rFIXFc is protective against bleeding as without measurable FIX activity in plasma, and no extra bleeding seems to occur. The physiologically based pharmacokinetic (PBPK) model for rFIXFc which we describe in this study, is able to accurately predict the observed concentration‐time profiles of rFIXFc in plasma and is able to quantify the binding of rFIXFc to Col4 in the extravascular space after an intravenous dose of 50 IU/kg rFIXFc in a male population. Our model predicts that the total AUC of rFIXFc bound to Col4 in the extravascular space is approximately 19 times higher compared to the AUC of rFIXFc in plasma. This suggests that rFIXFc present in the extravascular compartment may play an important role in achieving hemostasis after rFIXFc administration. Further studies on extravascular distribution of rFIXFc and the distribution profile of other EHL‐FIX concentrates are needed to evaluate the predictions of our PBPK model and to investigate its clinical relevance. [ABSTRACT FROM AUTHOR]

Acute variceal bleeding in cirrhosis represents a critical clinical event that significantly impacts patient prognosis, with mortality rates increasing further after a second episode. This underscores the need for immediate intervention and optimal prophylaxis. The creation of a transjugular intrahepatic portosystemic shunt (TIPS) has been proven to be highly effective for managing esophageal variceal bleeding. However, the use of TIPS for managing cardiofundal gastric varices and ectopic varices remains debated due to their unique vascular anatomy and the limited data available. These varices, although less prevalent than esophageal varices, are complex and heterogeneous vascular shunts between the splanchnic venous system and the systemic veins. Indeed, while endoscopic therapy with tissue adhesives is widely endorsed for achieving hemostasis in active hemorrhage, there is no consensus regarding the optimal approach for secondary prophylaxis. Recent research emphasizes the efficacy of endovascular techniques over endoscopic treatments, such as TIPS and endovascular variceal embolization techniques. This review examines the use of TIPS in managing acute variceal bleeding in patients with cirrhosis, focusing specifically on cardiofundal gastric varices and ectopic varices, discussing optimal patient care based on the latest evidence, aiming to improve outcomes for this challenging subset of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Heavy ion radiation, found in outer space and used in some cancer treatments, can damage vital cells in the intestines. Studies using mice show that this type of radiation causes long-lasting stress, accelerated aging, and harmful changes in these cells, which can perturb gut function and increase the risk of developing cancer. Specialized mouse models were employed to monitor how these intestinal stem cells are affected over time after exposure to this radiation. We found that particle radiation caused more stress-induced damage and tumor incidence compared to photon radiation. Intestinal stem cells showed signs of aging and inflammation, which persisted for up to a year. This ongoing stress and damage also disrupt the gut barrier's function and ability to absorb nutrients properly. The findings suggest that astronauts exposed to this radiation during deep space missions might face increased risks of gut dysfunction as well as increased cancer risk. Heavy ion radiation, prevalent in outer space and relevant for radiotherapy, is densely ionizing and poses a risk to intestinal stem cells (ISCs), which are vital for maintaining intestinal homeostasis. Earlier studies have shown that heavy-ion radiation can cause chronic oxidative stress, persistent DNA damage, cellular senescence, and the development of a senescence-associated secretory phenotype (SASP) in mouse intestinal mucosa. However, the specific impact on different cell types, particularly Lgr5+ intestinal stem cells (ISCs), which are crucial for maintaining cellular homeostasis, GI function, and tumor initiation under genomic stress, remains understudied. Using an ISCs-relevant mouse model (Lgr5+ mice) and its GI tumor surrogate (Lgr5+Apc1638N/+ mice), we investigated ISCs-specific molecular alterations after high-LET radiation exposure. Tissue sections were assessed for senescence and SASP signaling at 2, 5 and 12 months post-exposure. Lgr5+ cells exhibited significantly greater oxidative stress following 28Si irradiation compared to γ-ray or controls. Both Lgr5+ cells and Paneth cells showed signs of senescence and developed a senescence-associated secretory phenotype (SASP) after 28Si exposure. Moreover, gene expression of pro-inflammatory and pro-growth SASP factors remained persistently elevated for up to a year post-28Si irradiation. Additionally, p38 MAPK and NF-κB signaling pathways, which are critical for stress responses and inflammation, were also upregulated after 28Si radiation. Transcripts involved in nutrient absorption and barrier function were also altered following irradiation. In Lgr5+Apc1638N/+ mice, tumor incidence was significantly higher in those exposed to 28Si radiation compared to the spontaneous tumorigenesis observed in control mice. Our results indicate that high-LET 28Si exposure induces persistent DNA damage, oxidative stress, senescence, and SASP in Lgr5+ ISCs, potentially predisposing astronauts to altered nutrient absorption, barrier function, and GI carcinogenesis during and after a long-duration outer space mission. [ABSTRACT FROM AUTHOR]

Introduction: Hemostasis following large‐bore femoral vein access remains a challenge. Manual compression has been the standard of care but requires bedside staff, prolonged bed rest, and longer length of stay. The LockeT is an external compression device that attempts to address these issues while achieving venous hemostasis. Objectives: We evaluate postprocedural hemostasis and vascular closure outcomes after using LockeT following cardiac electrophysiologic procedures. Methods: We performed a single‐center, observational study of patients who underwent vascular closure for electrophysiology procedures using LockeT. Postprocedural outcomes were subsequently analyzed. Results: We studied 102 patients (N) for whom LockeT was used to close 182 separate vascular access sites (n). Common procedures were atrial fibrillation ablation (56.9%, N = 58) and left atrial appendage occlusion (28.4%, N = 29). Most often, 8‐Fr [48.3% (n = 126)], 11‐Fr [27.2% (n = 71)], and 8.5‐Fr [16.9% (n = 44)] sheaths were used, with an average procedure time of 82.1 ± 29.4 min. Hemostasis was achieved in 97.8% (n = 187) of all LockeT cases. Time to ambulation and discharge were 3.93 ± 1.10 h and 8.1 ± 4.4 h, respectively. No major complications were noted. Postprocedurally, 52% (N = 53) of patients were discharged on the same day. There were no differences in hemostasis (p =.859) or ambulation times (p =.202) between procedure types. Conclusion: The LockeT can effectively close venous access sites with no major complications. [ABSTRACT FROM AUTHOR]

Objective: To investigate the independent effects of irisin on insulin resistance (IR) in ovary of polycystic ovary syndrome (PCOS) and explore possible pathways. Methods: We established PCOS medel using Poretsky L's method, then PCOS rats were randomly divided into model group (M) and irisin group (I), and normal rats (N) were used as the control. Then rats in the group I were injected with recombinant irisin. Then the levels of circulating fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of IR (HOMA‐IR) and PI3K/AKT and MAPK/ERK pathways in each group were observed, as well as the effects of irisin on the levels of circulating HOMA‐IR and PI3K/AKT and MAPK/ERK pathways in ovary of PCOS rats were evaluated. Results: Compared with normal group, levels of FBG, FINS, and HOMA‐IR of model group were significantly increased (p < 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p‐PI3K, PI3K, p‐AKT, and AKT (p = 0.015, p = 0.010, p = 0.005, and p = 0.009, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.001, and p = 0.005, respectively) were decreased, while the levels of average optical density of p‐ERK, ERK (p = 0.011, and p = 0.013, respectively) and level of mRNA concentration of ERK (p < 0.001) were increased in ovary. After irisin intervention, compared with model group, levels of FBG, FINS, and HOMA‐IR of rats in irisin group were significantly decreased (p = 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p‐PI3K, PI3K, p‐AKT, and AKT (p = 0.030, p = 0.024, p = 0.012, and p = 0.025, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.002, and p = 0.003, respectively) were significantly increased, while the levels of average optical density of p‐ERK, ERK (p = 0.004, and p = 0.026, respectively) and level of mRNA concentration of ERK (p = 0.001) were significantly decreased. Conclusion: Our study demonstrated that irisin could not only improve circulating insulin resistance, but may also improve ovarian IR through an increase in the activity of PI3K/AKT signaling and a decrease of MAPK/ERK signaling. [ABSTRACT FROM AUTHOR]

Solitary plasmacytomas of clivus are a rare entity, having only less than 20 cases reported so far in the literature; its diagnosis and management don't have a gold standard. Although endoscopic skull base surgery (ESBS) is less morbid, it poses a challenge to the surgeon because of the critical location close to vital structures and intraoperative bleeding. Here we present a case report on managing this rare entity and our challenges while dealing with this vascular tumour. [ABSTRACT FROM AUTHOR]

Disorders of hemostasis resulting in bleeding or thrombosis are leading cause of mortality in the world. Blood platelets are main players in hemostasis, providing the primary response to the vessel wall injury. In this case, they rapidly switch to the activated state in reaction to the exposed chemical substances such as ADP, collagen and thrombin. Molecular mechanisms of platelet activation are known, and detailed computational models are available. However, they are too complicated for large-scale problems (e.g. simulation of the thrombus growth) where less detailed models are required, which still should take into account the variation of agonist concentration and heterogeneity of platelets. In this paper, we present a simple model of the platelet population response to a spatially inhomogeneous stimulus. First, computational nodes modeling platelets are placed randomly in space. Each platelet is assigned the specific threshold for agonist, which determines whether it becomes activated at a given time. The distribution of the threshold value in a population is assumed to be log-normal. The model was validated against experimental data in a specially designed system, where the photorelease of ADP was caused by localized laser stimulus. In this system, a concentration of ADP obeys 2-dimensional Gaussian distribution which broadens due to the diffusion. The response of platelets to the point-like source of ADP is successfully described by the presented model. Our results advance the understanding of platelet function during hemostatic response. The simulation approach can be incorporated into larger computational models of thrombus formation. [ABSTRACT FROM AUTHOR]

Introduction: Lower gastrointestinal bleeding (LGIB) is a common cause of emergency hospitalization and may require readmission for re-bleeding. A novel adhesive endoscopic hemostatic powder (UI-EWD/NexpowderTM, Nextbiomedical, Incheon, South Korea) has been developed and recently utilized for LGIB hemostasis. The aim of the current study was to assess the efficacy and safety of UI-EWD as a rescue therapy for the treatment of refractory LGIB. Methods: In this study, a total of 59 consecutive patients with LGIB who experienced initial hemostasis failure with conventional endoscopic therapy were enrolled into this multicenter single-arm study. These patients subsequently underwent UI-EWD application for the refractory LGIB hemostasis. We evaluated the success rate of hemostasis, re-bleeding rate within 30 d, and adverse events related to UI-EWD. Results: UI-EWD was successfully administered to the bleeding sites in all enrolled refractory bleeding patients. Hemostasis was achieved in the entirety of the 59 patients (100%). The cumulative re-bleeding rate within 30 d was 8.5% (5/59). There were no UI-EWD-related adverse events, such as perforation nor embolism. Conclusion: Based on our results, the utilization of UI-EWD demonstrated a remarkable success rate in achieving hemostasis for refractory LGIB, while also exhibiting promising outcomes in reducing the re-bleeding rate within a 30-day period. Particularly, UI-EWD exhibits a favorable safety profile across all segments of the colon in cases of refractory LGIB. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Unfractionated heparin is used as the most common anticoagulation for venovenous extracorporeal membrane oxygenation (VV ECMO) patients. However, it is accompanied by frequent bleeding and thrombotic complications. The aim of the study was to demonstrate the feasibility of Enoxaparin anticoagulation for VV ECMO patients.This study is a retrospective analysis of VV ECMO patients on continuous intravenous Enoxaparin anticoagulation. The primary outcome was the incidence of bleeding, thrombotic, and neurological complications during ECMO support. The secondary outcome was an analysis of secondary and primary hemostasis profiles.Data from 38 patients were analyzed in this study. The incidence of bleeding complications was 5.3%, for thrombotic complications it was 2.6% and for neurological (bleeding/ischemic events) complications it was 10.5%. The targeted anti‐Xa activity of 0.4–0.6 IU/mL was achieved and maintained during whole ECMO period in 28 patients (73.8%), not affecting the hemocoagulation profile represented by APTT‐r 1.15 ± 0.2, TT 18.67 ± 3.35 s, PT/INR 1.21 ± 0.19, fibrinogen 5.39 ± 1.49 g/L, antithrombin, and platelet count. Primary hemostasis pathology was diagnosed in all patients by PFA 200 tests Col/EPI 279 ± 38 s and Col/ADP 249 ± 66 s. The running time of ECMO was 7.8 ± 3.4 days.Enoxaparin anticoagulation appears to be feasible for VV ECMO patients without an increase in adverse events. Further larger‐sampled and comparative studies are needed in the future to support our findings. [ABSTRACT FROM AUTHOR]

Objective: About 3% of patients with lupus develop severe diffuse alveolar hemorrhage (DAH) with pulmonary vasculitis. C57BL/6 (B6) mice with pristane‐induced lupus also develop DAH, but BALB/c mice are resistant. DAH is independent of Toll‐like receptor signaling and other inflammatory pathways. This study examined the role of the MEK1/2 pathway (MEK1/2–ERK1/2, JNK, p38). Methods: B6 and BALB/c mice were treated with pristane with or without inhibitors of MEK1/2 (trametinib/GSK1120212 [GSK]), ERK1/2 (SCH772984 [SCH]), JNK, or p38. Effects on lung hemorrhage and hemostasis were determined. Results: GSK and SCH abolished DAH, whereas JNK and p38 inhibitors were ineffective. Apoptotic cells were present in lung samples from pristane‐treated mice but not in mice receiving pristane and GSK, and endothelial dysfunction was normalized. Expression of the ERK1/2‐regulated transcription factor early growth response 1 increased in pristane‐treated B6, but not BALB/c, mice and was normalized by GSK. Pristane also increased expression of the anticoagulant genes Tfpi and Thbd in B6 mice. The ratio of Tfpi to tissue factor (F3) to Tfpi increased in B6 (but not BALB/c) mice and was normalized by GSK. Circulating thrombomodulin protein levels increased in B6 mice and returned to normal after GSK treatment. Consistent with augmented endothelial anticoagulant activity, pristane treatment increased tail bleeding in B6 mice. Conclusion: Pristane treatment promotes lung endothelial injury and DAH in B6 mice by activating the MEK1/2–ERK1/2 pathway and impairing hemostasis. The hereditary factors determining susceptibility to lung injury and bleeding in pristane‐induced lupus are relevant to the pathophysiology of life‐threatening DAH in systemic lupus erythematosus and may help to optimize therapy. [ABSTRACT FROM AUTHOR]

Genetic sequencing technologies are evolving at a rapid pace with major implications for research and clinical practice. In this review, the authors provide an updated overview of next-generation sequencing (NGS) and emerging methodologies. NGS has tremendously improved sequencing output while being more time and cost-efficient in comparison to Sanger sequencing. The authors describe short-read sequencing approaches, such as sequencing by synthesis, ion semiconductor sequencing, and nanoball sequencing. Third-generation long-read sequencing now promises to overcome many of the limitations of short-read sequencing, such as the ability to reliably resolve repeat sequences and large genomic rearrangements. By combining complementary methods with massively parallel DNA sequencing, a greater insight into the biological context of disease mechanisms is now possible. Emerging methodologies, such as advances in nanopore technology, in situ nucleic acid sequencing, and microscopy-based sequencing, will continue the rapid evolution of this area. These new technologies hold many potential applications for hematological disorders, with the promise of precision and personalized medical care in the future. [ABSTRACT FROM AUTHOR]

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices—such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass—require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices. [ABSTRACT FROM AUTHOR]

The contact pathway of blood clotting has received intense interest in recent years as studies have linked it to thrombosis, inflammation, and innate immunity. Because the contact pathway plays little to no role in normal hemostasis, it has emerged as a potential target for safer thromboprotection, relative to currently approved antithrombotic drugs which all target the final common pathway of blood clotting. Research since the mid-2000s has identified polyphosphate, DNA, and RNA as important triggers of the contact pathway with roles in thrombosis, although these molecules also modulate blood clotting and inflammation via mechanisms other than the contact pathway of the clotting cascade. The most significant source of extracellular DNA in many disease settings is in the form of neutrophil extracellular traps (NETs), which have been shown to contribute to incidence and severity of thrombosis. This review summarizes known roles of extracellular polyphosphate and nucleic acids in thrombosis, with an emphasis on novel agents under current development that target the prothrombotic activities of polyphosphate and NETs. [ABSTRACT FROM AUTHOR]

Surgical success includes a planned incision, achieving haemostasis, good mechanical closure and optimal maintenance of the surgical wound. New materials, as tissue adhesives, have been suggested as substitutes for sutures, to overcome their disadvantages. This study aimed at gathering the differences of using surgical adhesives in oral surgery compared with the conventional method of using sutures as a wound closure technique. PRISMA analyses, PICO criteria and PubMed/Medline database, EBSCO and Cochrane Library were used for research. Inclusion criteria included prospective, randomized controlled trials and case–control studies published in English with full access, where clinical advantages and demerits/limitations were reported in patients who underwent oral surgical incisions, without time restrictions. Exclusion criteria comprised literature with lower level of evidence. A total of 15 studies were assessed and analysed 15 parameters as alternatives to sutures (100%), cost‐effectiveness (6,6%), postoperative pain (53,3%), time consumption (73,3%), haemostasis (46,6%), homeostasis (13,3%), aids healing (26,6%), tissue inflammation (26,6%), safety (6,6%), graft dimension (3,13), biocompatibility (13,3%), adhesion to tissue (6,6%), bacteriostatic effect (20%), oedema (13,3%) and ease of application (26,6). Selected articles' results indicate that surgical glues can be a suitable alternative and/or adjuvant to oral sutures, presenting numerous advantages. [ABSTRACT FROM AUTHOR]

It is urgently demanded to develop biomaterials with balanced hemostatic/antibacterial ability and facile preparation methods. In this work, cationic starch microparticles (MSQP), prepared by the facile grafting of microporous starch particles (MS) with tunable quaternized polyethyleneimine, were readily constructed as promising hemostatic materials for integrated antibacterial and hemostatic performance. The cationic grafts not only endowed MSQP with good antibacterial ability, but also benefited from biocompatible MS to achieve favorable biocompatibility. Moreover, in vitro results confirmed the superior hemostatic property of MSQP2 (with the medium content of cationic grafts) among three MSQP and pristine MS. After investigating the blood-material interactions of MSQP/MS, the procoagulant mechanism of MSQP2 was revealed that the optimal amount of cationic grafts achieves highly balanced plasma-protein adhesion, platelet adhesion and blood coagulation system. In vivo artery-injury model further demonstrated the superior hemostatic performance of MSQP2 for potential severe hemorrhage. This work sheds light on the design of cationic polymer-based biomaterials for balanced antibacterial and hemostatic functions. [ABSTRACT FROM AUTHOR]

Context Breastfeeding is associated with a reduced maternal risk for cardiovascular diseases (CVDs). Objective Since the underlying mechanisms are still poorly understood, we here examined the effect of breastfeeding on the plasmatic coagulation system in women with and without history of gestational diabetes mellitus (GDM). Methods A total of 76 participants of the German Gestational Diabetes Study (PREG; NCT04270578) were examined 14 months (interquartile range [IQR], 12-26 months) after delivery with a 5-point oral glucose tolerance test. Global coagulation tests, prothrombotic coagulation proteins (FII/FVII/FVIII/FIX), antithrombotic proteins (antithrombin, protein C/S), and endothelial markers (von Willebrand factor and plasminogen activator inhibitor 1) were determined. The Framingham risk score was used to estimate the 10-year CV risk. The effect of breastfeeding duration on coagulation was analyzed using multivariable linear models. Results The mean duration of breastfeeding was 11 months (IQR, 7-14 months). Overall, longer duration of breastfeeding was associated with lower CV risk (Framingham risk score; P =.05) and was negatively associated with FIX (P =.018). We detected an interaction between previous GDM and breastfeeding duration for FIX (P Interaction =.017): Only in women with GDM history was the duration of breastfeeding negatively associated with FIX activity (P =.016). This association persisted in statistical models adjusted for age, body mass index, insulin sensitivity, and C-reactive protein. The duration of breastfeeding was not associated with anticoagulant proteins and endothelial markers. Conclusion Longer duration of breastfeeding is associated with lower CV risk and an improved coagulation profile. Women with GDM history appear to benefit particularly from prolonged breastfeeding. [ABSTRACT FROM AUTHOR]

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Background: Fibrin sealants are increasingly used in head and neck surgery to aid hemostasis, but individual studies lack conclusive evidence. This systematic review investigates their effectiveness compared to placebo or usual care in head and neck surgery. Methods: Studies comparing fibrin sealant to placebo or usual care in patients 18 years or older who have undergone soft tissue surgery of the head and neck with drain placement were included. Primary outcomes include wound complications and time to surgical drain removal postoperatively. Secondary outcomes include length of hospital stay, drain volume output, surgical management of hematoma, blood transfusion rates, and adverse reactions. Electronic databases were searched on October 2023 for randomized controlled and quasi-experimental studies. Studies underwent independent screening, review, and appraisal by two reviewers using JBI appraisal tools. Certainty was assessed with GRADE, and meta-analysis was conducted using JBI SUMARI, presenting effect sizes as relative risk ratios or mean differences with 95% confidence intervals. Results: Fourteen studies were included examining 904 patients. The fibrin sealant group exhibited reduced postoperative wound complications (hematoma, seroma, wound dehiscence, wound infection) (RR = 0.64, 95% CI = 0.45–0.92), shorter drain removal times (MD = − 0.49 days, 95% CI = − 0.68 to − 0.29), decreased drain output (MD = − 16.52 mL, 95% CI = − 18.56 to − 14.52), and shorter hospital stay (MD = − 0.84 days, 95% CI = − 1.11 to − 0.57) compared to controls. There was no statistically significant difference on the rate of intervention for postoperative hematoma and the rate of adverse reactions. Discussion: Evidence demonstrates with low certainty that fibrin sealant use is associated with a modest reduction in the rate of wound complications, drain duration, and length of stay, and a small reduction in drain volume output. Methodological weaknesses and clinical heterogeneity limit these findings. Further research should focus on enhancing methodological quality and exploring the cost-effectiveness of fibrin sealant use in surgery. Systematic review registration: CRD42023412820. Funding: Nil. [ABSTRACT FROM AUTHOR]

Introduction Aim Methods Results Conclusion Acquired von Willebrand syndrome (AVWS) is a rare haemorrhagic disorder. The prophylaxis and treatment of bleeding before surgery are complex. Since 2018, a new recombinant VWF (rVWF) concentrate that contains no factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France.To describe the real‐world experience of using rVWF in non‐surgical bleeding and surgical procedures in patients with AVWS.Fifteen bleeding episodes in seven patients and 16 surgeries in 10 patients were retrospectively analysed in t French haemostasis centres.During bleeding, the median number of infusions was only 1 (range 1–27) with a median loading dose of 58 IU/kg (range 17–116) rVWF and a total median dose of 65 IU/kg (range 35–1488) rVWF. Bleeding control was rated markedly effective in 73% (11/15) of the cases and ineffective in 27% (4/15).During surgeries, the median number of infusions was 3 (range 1–8) with a preoperative loading dose of 60 IU/kg (range 23–118) rVWF and a total median dose of 123 IU/kg (range 31–542). The overall clinical efficacy was qualified as excellent, good and poor (ISTH criteria) in respectively 7 (43%), 6 (38%) and 3 (19%) procedures.There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events nor adverse events were reported.This French ‘real‐world’ experience shows that rVWF could be of interest in the treatment and prophylaxis of bleeding in patients with AVWS, with no clinically significant safety concern. [ABSTRACT FROM AUTHOR]

Background: The effect of acidemia on blood coagulation remains inadequately understood in veterinary medicine. Therefore, we assessed the effect of in vitro acidification of canine whole blood on coagulation and investigated whether acidemia-induced coagulopathy could be reversed by reversing acidemia. Methods: Citrated whole blood samples were taken from six healthy Beagle dogs and categorized, based on pH adjustment, into neutral, weak acidemia (WA), strong acidemia (SA), and reversal from SA. Then, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, conventional thromboelastography (TEG) parameters, and velocity curve (V-curve) variables of TEG were assessed. Results: The PT, aPTT, and most TEG parameters showed significant coagulopathy in the SA group compared to the neutral group, with additional significant changes in reaction time (R), clot kinetic (K), maximum amplitude (MA), split point (SP), elasticity (E), thrombodynamic potential index (TPI), and coagulation index (CI) between the SA and WA groups. Among V-curve variables, the maximum rate of thrombus generation (MRTG) and total thrombus generation were significantly inhibited in the SA group compared to the neutral group, with significant differences in the time to maximum rate of thrombus generation (TMRTG) between the WA and SA groups. In the reverse group, aPTT, R, K, α-angle, MRTG, TMRTG, SP, TPI, and CI exhibited significant recovery compared to the SA group. Conclusion: The in vitro induction of acidemia in canine whole blood leads to impairment of coagulation profiles, and pH correction can reverse most acidemia-induced coagulopathy. [ABSTRACT FROM AUTHOR]

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders. [ABSTRACT FROM AUTHOR]

O-linked β-N-acetylglucosamine (O-GlcNAc, O-GlcNAcylation) is a post-translational modification of serine/threonine residues of proteins. Alterations in O-GlcNAcylation have been implicated in several types of cancer, regulation of tumor progression, inflammation, and thrombosis through its interaction with signaling pathways. We aim to explore the relationship between O-GlcNAcylation and hemostasis, inflammation, and cancer, which could serve as potential prognostic tools or clinical predictions for cancer patients' healthcare and as an approach to combat cancer. We found that cancer is characterized by high glucose demand and consumption, a chronic inflammatory state, a state of hypercoagulability, and platelet hyperaggregability that favors thrombosis; the latter is a major cause of death in these patients. Furthermore, we review transcription factors and pathways associated with O-GlcNAcylation, thrombosis, inflammation, and cancer, such as the PI3K/Akt/c-Myc pathway, the nuclear factor kappa B pathway, and the PI3K/AKT/mTOR pathway. We also review infectious agents associated with cancer and chronic inflammation and potential inhibitors of cancer cell development. We conclude that it is necessary to approach both the diagnosis and treatment of cancer as a network in which multiple signaling pathways are integrated, and to search for a combination of potential drugs that regulate this signaling network. [ABSTRACT FROM AUTHOR]

Uncontrollable bleeding caused by accidental severe trauma and organ operation severely affects people's life safety, even leading to death. Therefore, it is important to cease the bleeding quickly and effectively. Here, we report a rapid photocrosslinking hydrogel (DP‐F127 hydrogel) based on F127 and acrylate functional motifs for in situ emergency hemostasis. The acrylate groups in DP‐F127 can be cross‐linked within 10 s by UV irradiation. The resulted hydrogels exhibit excellent mechanical properties, biocompatibility, and rapid hemostatic ability. The in vivo studies on the DP‐F127 hydrogel demonstrated that liver bleeding could be rapidly repaired and show significantly less blood loss than commercially available dressing (Gelatin sponge, GS). This study provides a new paradigm for developing a hemostatic hydrogel with the rapid speed of crosslinking for in situ emergency hemostasis. [ABSTRACT FROM AUTHOR]

Background: Aortoesophageal fistula (AEF) is a rare cause of upper gastrointestinal hemorrhage. Despite diagnostic and therapeutic advances, the mortality rate in AEF patients remains high because of its fulminant course, even with maximal intensive care. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a resuscitation technique to control life-threatening bleeding. It has become an important modality in the management of life-threatening, traumatic or non-traumatic, arterial bleeding. However, it's use in hemorrhagic shock caused by cancer has rarely been reported. Case presentation: A 51-year-old woman with a history of esophageal cancer presented to our emergency department with hematemesis. Computed tomography was performed because of a strong suspicion of hemorrhagic shock. With a diagnosis of AEF due to esophageal cancer, emergency thoracic endovascular aortic repair was performed while the bleeding was controlled using REBOA. Staged elective esophageal reconstruction was successfully performed. Conclusions: Hemostasis is crucial in patients who present with suspected hemorrhagic shock attributable to AEF. The timely implementation of REBOA has shown promise and potential effectiveness in such cases. [ABSTRACT FROM AUTHOR]

An asymmetrical wound dressing functions akin to human skin by serving as a protective barrier between a wound and its immediate environment. However, significant challenges persist concerning the robust adhesion and asymmetrical adhesion properties of hydrogels, particularly when applied in emergency hemostasis and wound healing contexts. Herein, the study has successfully synthesized hydrogel patches with Janus asymmetric‐adhesion, denoted as HGO‐C, exclusively comprised of natural polymers. This achievement is realized through the assembly of adhesive hydrogel (HGO) and non‐adhesive hydrogel (CGC), thereby amalgamating their distinct functionalities. The non‐adhesive hydrogel component served as a physical shield and safeguarding the wound against contamination, while the adhesive hydrogel, when in contacted with the wound surface, firmly adhered to it, swiftly arresting bleeding and facilitating wound healing. Cytocompatibility tests, hemolysis tests, antibacterial assays, and coagulation assays demonstrated excellent biocompatibility, antibacterial, and hemostatic properties of HGO‐C. Finally, the in vivo experiments, including a liver hemorrhage assay and a wound healing assay, unequivocally showed the rapid hemostatic and enhanced wound healing capabilities of HGO‐C. Consequently, these distinctive hydrogel patches, derived from natural polymers and characterized by their asymmetric adhesion properties, may have great potential for real‐life usage in clinical patients. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a progressively prevalent global health issue. During the initial phases of the condition, CKD is commonly linked to a tendency for excessive blood clotting. While in the end-stage of disease, patients undergoing hemodialysis have a multitude of hemostatic abnormalities. These include prolonged bleeding time, altered platelet count, prolonged PT and aPTT, elevated FDPs and D-dimer, dysregulated vWF activity, and abnormal thrombin generation. These changes result from a combination of uremic toxicity, endothelial dysfunction, inflammatory states, and the effects of the hemodialysis procedure itself. Understanding these mechanisms is crucial for managing and mitigating the bleeding and thrombotic risks in this patient population. This review aims to systematically investigate the effects of hemodialysis on key hemostasis parameters in CKD patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the accuracy of a point‐of‐care coagulation analyzer (POCCA) with a reference laboratory coagulation analyzer (LabCA) and to evaluate for confounding factors that could alter the performance of the POCCA. Design: Prospective, observational study. Setting: Two university veterinary teaching hospitals. Animals: Forty‐three client‐owned dogs undergoing coagulation testing between April 2020 and June 2021. Methods: Samples were obtained from dogs undergoing coagulation testing as part of a diagnostic workup. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured on the POCCA and on the LabCA. PCV, platelet count, total plasma protein, hyperbilirubinemia, hemolysis, lipemia, and autoagglutination were recorded. Results: Moderate correlation was seen for PT and strong correlation was seen for aPTT between the POCCA and the LabCA (PT: 0.59, P < 0.0001; aPTT: 0.71, P < 0.0001). The POCCA results were consistent with normal or hypocoagulable samples for 30 of 38 PT and 33 of 37 aPTT results, as identified by the LabCA. Samples with PCV of 30%–55% were moderately correlated (PT: 0.63, P = 0.0004; aPTT: 0.63, P = 0.0003), but those outside that range were more likely to register an error message on the POCCA or provide disparate results. When hemolysis was present, there was a weak correlation between the POCCA and the LabCA for PT (rho: 0.38 [95% confidence interval: 0.19–0.76], P = 0.18) and a strong correlation for aPTT (rho: 0.86 [95% confidence interval: 0.62–0.95], P < 0.0001). Samples with hyperbilirubinemia were strongly correlated for PT (0.97, P = 0.002) but not for aPTT. Lipemia and autoagglutination were not observed. Conclusion: There was an acceptable correlation in patients with PCV within the manufacturer's recommended reference range; however, measurements on samples with PCV outside the reference range were inconsistent with the LabCA. Caution should be used when using the POCCA in patients with coagulopathy and anemia or other potential confounders. [ABSTRACT FROM AUTHOR]

We present two critical cases of life‐threatening postpartum hemorrhage (PPH) due to amniotic fluid embolism (AFE) complicated by disseminated intravascular coagulopathy (DIC). These cases are the first to show the effectiveness of resuscitative endovascular balloon occlusion of the aorta (REBOA) for patient survival. In Case 1, the patient, experiencing critical conditions with severe PPH and DIC despite conventional treatments, including rapid blood transfusion and fibrinogen concentrate, was air‐transferred to our hospital, where REBOA was promptly employed before hysterectomy was completed. Case 2 involved an ambulance‐transferred patient with massive PPH and DIC despite conventional treatments. Prehospital REBOA was performed to prevent cardiac arrest during transfer, and hysterectomy was performed in the hospital. Given the rapid deterioration associated with AFE, REBOA can serve as a bridge until complete hemostasis to maintain vital signs and control bleeding in patients unresponsive to standard therapies before hemostatic interventions or during transfer. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the noninferiority of the novel hemostatic agent, Hemofence (BMI Korea Co., Ltd., thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety. Methods: This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study. Investigational drugs were administered to the first and second bleeding sites of each participant (or only to the first site if a second site was absent), evaluating hemostasis success rate within 10 minutes and the time to achieve hemostasis. Subsequent visits were conducted for safety assessments. For noninferiority test, a 97.5% one-sided confidence interval (CI) was used; the test group was deemed noninferior if the lower limit exceeded -10%. Results: This trial showed a 97.10% success rate in the test group and 96.05% in the control group for primary efficacy. The 95% CI (-4.90% to 7.44%) confirmed the test drug's noninferiority. Time to hemostasis showed no significant difference between groups. All adverse events, adverse drug reactions, and serious adverse events were statistically similar between groups (p=1.000, p=0.243, and p=0.966, respectively). Conclusion: A novel hemostatic agent, Hemofence, demonstrated an efficacy and safety profile comparable to that of Floseal. [ABSTRACT FROM AUTHOR]

Significant advancements have shaped the landscape of anticoagulant therapy in the past two decades, including the introduction of direct oral anticoagulants (DOACs), characterized by favorable safety and efficacy profiles and reduced drug-to-drug or food interaction resulting in excellent patient compliance. However, residual concerns still exist with standard-of-care anticoagulant therapy, including the inability to use DOACs in several clinical settings and the need to further reduce the risk of bleeding. Recent improvements in the understanding of the mechanisms behind thrombus formation have led to the awareness that the intrinsic pathway of the coagulation cascade may play an important role in pathological thrombosis, but not in hemostasis. This has represented the rationale for targeting this pathway with factor XI (FXI) inhibitors, with the aim of uncoupling hemostasis and thrombosis. Clinical evidence from patients with FXI deficiency further supports this concept. A number of compounds with different mechanisms of action have been developed to target FXI (i.e., asundexian, abelacimab, Ionis-FXIRx, milvexian, osocimab, and Xisomab 3G). To date, the majority of available trials have not gone beyond completion of phase 2 and results are conflictive making it difficult to appraise the clinical benefit of these compounds in the different clinical settings where they have been tested (i.e., atrial fibrillation, acute ischemic stroke, acute myocardial infarction, end-stage renal disease, total knee arthroplasty). Moreover, the largest phase 3 randomized trial designed to test the efficacy of asundexian over apixaban in patients with atrial fibrillation, the OCEANIC-AF, has been prematurely stopped as a result of the inferior efficacy of asundexian. In this review we discuss the pharmacological properties and available evidence generated thus far for factor XI inhibitors, providing a perspective on the current state of these drugs. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the blood protective effect of autologous platelet-rich plasma in aortic root reconstruction under longtime cardiopulmonary bypass. Method: Patients who underwent aortic root reconstruction between August 2018 and August 2022 were included and divided into experimental and control groups according to whether autologous platelet-rich plasmapheresis was used or not. The experimental group included 112 patients (90 males aged 39.00 [28.75–49.00] years), and the control group included 112 patients (90 males aged 37.00 [27.00–46.25] years). The clinical data for example EuroSCORE II cardiovascular surgery risk score, blood routine and other indicators were collected from the two groups. Results: The transfusion volume of allogeneic red blood cells in the experimental group (52 cases without blood transfusion, 23 cases with 1–2 units, 15 cases with 3–4 units, and 22 cases with 5 units and above) was significantly lower than that in the control group (32 cases without transfusion, 34 cases with 1–2 units, 22 cases with 3–4 units, and 24 cases with 5 units or more) (Z = −2.06, p < 0.05). Resternotomy/thoracotomy occurred in 11 cases (9.8%) in the experimental group and 23 cases (20.5%) in the control group (RR = 2.37, 95% CI: 1.1–5.14, p < 0.05). The number of bleeding events in the experimental group (18 cases, 16.1%) was significantly less than that in the control group (33 cases, 29.5%) (RR = 2.18, 95% CI: 1.14–4.17, p < 0.05). Conclusions: The application of autologous platelet-rich plasma in a long-time cardiopulmonary bypass aortic root reconstruction can reduce the amount of allogeneic blood transfusion and the occurrence of bleeding events, which is beneficial for blood protection. [ABSTRACT FROM AUTHOR]

Background/Aims: Advanced pancreatic and biliary tract cancers can invade the duodenum and cause duodenal hemorrhagic stenosis. This study aimed to evaluate the efficacy of covered self-expandable metal stents in the treatment of cancer-related duodenal hemorrhage with stenosis. Methods: Between January 2014 and December 2016, metal stents were placed in 51 patients with duodenal stenosis. Among these patients, a self-expandable covered metal stent was endoscopically placed in 10 patients with hemorrhagic duodenal stenosis caused by pancreatobiliary cancer progression. We retrospectively analyzed the therapeutic efficacy of the stents by evaluating the technical and clinical success rates based on successful stent placement, degree of oral intake, hemostasis, stent patency, and overall survival. Results: The technical and clinical success rates were 100%. All 10 patients achieved a gastric outlet obstruction scoring system score of three within two weeks after the procedure and had no recurrence of melena. The median stent patency duration and overall survival after stent placement were 52 days (range, 20-220 days) and 66.5 days (range, 31-220 days), respectively. Conclusions: Endoscopic placement of a covered metal stent for hemorrhagic duodenal stenosis associated with pancreatic or biliary tract cancer resulted in duodenal hemostasis, recanalization, and improved quality of life. [ABSTRACT FROM AUTHOR]

Chronic radiation proctitis, although relatively rare, can be the source of severe comorbidity in patients who had undergone prior radiotherapy for pelvic malignancy. Although current treatments for radiation proctitis include argon plasma coagulation, heater probe, bipolar neodymium/yttrium aluminum garnet (Nd: YAG) lasers, these interventions are often burdened by the frequent occurrence of rectal ulcerations and stenosis. Since radiofrequency ablation (RFA) is frequently used to ablate esophageal malignancy and pre-malignancy, we report the efficacy of RFA using through the scope system in two patients with rectal bleeding due to radiation proctitis. In both cases, the procedure was well-tolerated with hemostasis achieved after 1 or 2 sessions of RFA. Mucosal re-epithelialization was observed in areas of previous bleeding with no stenosis or ulceration observed at follow-up. [ABSTRACT FROM AUTHOR]

Introduction: In 2023, a group of experts proposed that a definition of major bleeding in pharmaceutically anticoagulated patients be used in all snakebite trials. This includes bleeding that results in death, is life-threatening, causes chronic sequelae, or consumes major healthcare resources, including bleeding into a major area or hemoglobin concentration decrease ≥20 g/L. We hypothesized that a decline in hemoglobin concentration ≥20 g/L is common but rarely clinically significant in our population of Arizona rattlesnake bite patients. Methods: Poison center records of rattlesnake bites in humans from 2018 through 2022 were retrospectively reviewed and assessed for major bleeding by the above criteria. Results: Four hundred and eighty-one patients met the inclusion criteria, of whom 265 (55.1%) had a hemoglobin concentration decrease ≥20 g/L. No patients died, and there was no evidence of bleeding into a critical organ. Three patients (1.1%) received blood transfusions. A decrease in hemoglobin concentration ≥20 g/L was 100% sensitive for identifying the major bleeding-associated outcomes; however, specificity was only 45.2%. Measures of healthcare utilization and chronic sequelae were somewhat higher in patients with a decrease in hemoglobin concentration ≥20 g/L. Discussion: Laboratory manifestations of hemotoxicity were common in this population, but hemorrhage was rare. While over half of patients met the major bleeding criterion of a decline in hemoglobin concentration ≥20 g/L, only 1.1% had bleeding that was potentially life-threatening as measured by receipt of a red blood cell transfusion. None died or had bleeding into a critical area. While nonspecific for major bleeding, a drop in hemoglobin concentration correlated with worse envenomation severity: these patients received more vials of antivenom, had a higher medical bill, a longer hospital stay, and were less likely to report full recovery at 90 days. Conclusions: A decrease in hemoglobin concentration ≥20 g/L should not be used as evidence of major bleeding for Arizona rattlesnake envenomation studies, but it may have a role as an indirect marker of envenomation severity. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This trial was to shorten the duration of both vasoconstrictors and prophylactic antibiotics to only 2 days in the therapy of acute gastroesophageal variceal hemorrhage. METHODS: After successful endoscopic hemostasis of gastroesophageal variceal hemorrhage, eligible patients were randomized to receive terlipressin infusion 1 mg per 6 hours and ceftriaxone 1 g daily for 5 days (group A) or a similar regimen for 2 days (group B). Primary end points were very early rebleeding at 5 days, and secondary end points included 48-hour hemostasis, 42-day rebleeding, and hospitalization days. RESULTS: Group A comprised 48 patients, and group B comprised 52 patients. Both groups were comparable in the severity of liver disease. Forty-eight-hour initial hemostasis was 95.8% in group A and 100% in group B (P = 0.13). Very early rebleeding between 3 and 5 days occurred in 1 patient (2.1%) in group A and 2 patients (3.8%) in group B (P = 0.60). The difference was 1.8% and the 95% confidence interval was -1.31% to 2.08%, which demonstrated noninferiority. Forty-two-day rebleeding occurred in 5 patients (10.4%) in group A and 4 patients (7.7%) in group B (P = 0.63). The median hospitalization days were 8.5 ± 3.8 days in group A vs 5.6 ± 2.6 days in group B (P < 0.001). DISCUSSION: After successful endoscopic hemostasis of acute variceal bleeding, combination of 2-day terlipressin infusion and ceftriaxone therapy was not inferior to the 5-day regimen in terms of very early rebleeding, with the advantage of shortening hospitalization stay. [ABSTRACT FROM AUTHOR]

Le bilan d'hémostase standard (taux de prothrombine [TP] et temps de céphaline avec activateur [TCA]) est très couramment prescrit mais son interprétation peut poser problème pour les cliniciens. Nous rappelons ici les bases de la démarche diagnostique devant ces tests. Seule une connaissance très basique de la cascade de la coagulation est nécessaire pour identifier les dosages de facteurs de la coagulation à prescrire et interpréter les résultats. En cas de déficit en plusieurs facteurs, on s'orientera vers une insuffisance hépatocellulaire, une coagulation intravasculaire disséminée ou une carence en vitamine K. Devant la baisse d'un seul facteur de la coagulation, nous rappelons les différentes causes de déficits acquis et évoquons brièvement les caractéristiques des différents déficits congénitaux qui relèvent généralement d'une prise en charge spécialisée. L'anticoagulant circulant de type lupique est une cause fréquente et généralement bénigne d'allongement du TCA à connaître, ne devant pas faire craindre un risque hémorragique. Une bonne connaissance de la démarche diagnostique devant une anomalie du TP ou du TCA permet généralement de débrouiller les situations les plus courantes. The standard hemostasis workup [quick time (QT), and activated partial thrombin time (APTT)] is very commonly prescribed but its interpretation is often difficult for practitioners who are not specialized in hemostasis. Here, we review the principles of the diagnostic approach to these tests. Only a very basic knowledge of the coagulation cascade is necessary to identify which clotting factor tests to prescribe and to interpret the results. Deficiency in several clotting factors suggests liver dysfunction, disseminated intravascular coagulation (DIC) or vitamin K deficiency. If a single factor is deficient, we review the different causes of acquired deficiencies and briefly discuss the characteristics of the different congenital defects, which generally require specialized management. Lupus anticoagulant is a common and generally benign cause of prolonged APTT to be aware of, which is not related to a hemorrhagic risk. A good knowledge of the diagnostic approach to abnormal QT or APTT generally allows the resolution of the most common situations. [ABSTRACT FROM AUTHOR]

The article presents an update review of pediatric facial lacerations, including considerations to take into account when evaluating facial or scalp laceration, options for anesthetics, anxiolysis and sedation, importance of proper wound preparation to the success of laceration repair, suture material/needle size and alternatives to sutures, approximation technique, postrepair care and use of antibiotics.

Background First-line over-the-scope (OTS) clip treatment has shown higher efficacy than standard endoscopic therapy in acute nonvariceal upper gastrointestinal bleeding (NVUGIB) from different causes. We compared OTS clips with through-the-scope (TTS) clips as first-line mechanical treatment in the specific setting of peptic ulcer bleeding. Methods We conducted an international, multicenter randomized controlled trial on consecutive patients with suspected NVUGIB. Patients with Forrest Ia–IIb gastroduodenal peptic ulcer were randomized 1:1 to OTS clip or TTS clip treatment. The primary outcome was the rate of 30-day rebleeding after successful initial hemostasis. Secondary outcomes included the rates of successful initial hemostasis and overall clinical success, defined as the composite of successful initial hemostasis and no evidence of 30-day rebleeding. Results 251 patients were screened and 112 patients were randomized to OTS (n = 61) or TTS (n = 51) clip treatment. The 30-day rebleeding rates were 1.6% (1/61) and 3.9% (2/51) in patients treated with OTS clips and TTS clips, respectively (Kaplan–Meier log-rank, P = 0.46). Successful initial hemostasis rates were 98.4% (60/61) in the OTS clip group and 78.4% (40/51) in the TTS clip group (P = 0.001). Overall clinical success rates were 96.7% (59/61) with OTS clips and 74.5% (38/51) with TTS clips (P = 0.001). Conclusions Low rates of 30-day rebleeding were observed after first-line endoscopic treatment of acute peptic ulcer bleeding with either OTS or TTS clips. However, OTS clips showed higher efficacy than TTS clips in achieving successful initial hemostasis and overall clinical success. [ABSTRACT FROM AUTHOR]