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The role of aspirin in cardiovascular primary prevention remains controversial. There are physiological reasons to explore its potential benefits in patients with high levels of lipoprotein(a) [Lp(a)], mainly due to its antifibrinolytic properties and interactions with platelets. The primary objective of this systematic review was to evaluate the cardiovascular benefits and bleeding risks associated with aspirin use in patients who have elevated Lp(a) levels but no history of cardiovascular disease. This systematic review was conducted following PRISMA guidelines. We performed a literature search to identify studies assessing the cardiovascular benefits and bleeding risks of aspirin use in patients with elevated Lp(a) levels (or a related genetic variant) who have no history of cardiovascular disease. Five studies (49,871 individuals) were considered for this systematic review. Three studies assessed the impact of aspirin use in relation to genetic variants associated with elevated Lp(a) levels (SNP rs379822), while the remaining two studies directly measured plasma levels of Lp(a). The endpoints evaluated varied among the studies. Overall, the findings consistently show that carriers of the apolipoprotein(a) variant or patients with Lp(a) levels > 50 mg/dL experience a reduction in cardiovascular risk with aspirin use. No significant bleeding issues were observed, although such events were reported in only two studies. This systematic review suggests that aspirin use in patients with elevated Lp(a) levels and no prior cardiovascular history may reduce cardiovascular risk. The available data on bleeding risk is insufficient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The resuscitative endovascular balloon occlusion of the aorta (REBOA) technique controls abdominal, pelvic, junctional, and postpartum hemorrhage via aortic endoclamping. There are no protocols or clear indications guiding REBOA use in a two-tiered prehospital emergency medical system, as found in France. We conducted a Delphi study to clarify the indications and contraindications for REBOA application in such a system., Methods: We performed a Delphi study in three rounds with an international group of doctors with REBOA expertise and clinical experience (members of the EndoVascular and Trauma Management Society). Based on the consensus answers, complemented by existing data in the literature, we developed a protocol for REBOA use in a medicalized prehospital setting., Results: We identified 10 questions that were not answered in the literature and submitted them to 21 experts. Over three rounds, consensus was reached on these 10 questions. The most important ones were "In your opinion, in a hemorrhagic patient, vascularly well-filled and whose hemodynamics remain unstable with 3mg/h of norepinephrine, should we inflate a REBOA to prevent the patients death and get them to the operating room alive?" and "In the case of REBOA placement (zone I) in the prehospital setting, would you agree that the maximum occlusion duration is approximately 30 minutes, with a partial or intermittent occlusion when possible?", Conclusion: We propose a protocol for REBOA use in a medicalized prehospital setting. This protocol clarifies that hemorrhagic shock, despite a noradrenaline (also known as norepinephrine) dose of 0.6µg/kg/min, is considered too serious for the patient to be transported to the trauma center without REBOA. Moreover, it clarifies that a zone 1 REBOA should be inflated for maximum 30 minutes and with a partial occlusion strategy, if possible. This protocol should be updated based on feedback following the establishment of prehospital REBOA and large randomized studies., Competing Interests: The authors have no conflict of interests to disclose., (2024.)

Objectives: Haemophilia B (HB), characterised by deficient factor IX (FIX), leads to spontaneous bleeds. Severe cases require prophylactic FIX replacement. This post hoc analysis assessed the first spontaneous bleeds among previously untreated patients (PUPs) with HB treated with recombinant FIX Fc fusion protein (rFIXFc) (NCT02234310) to identify factors influencing bleeds., Methods: Subjects included paediatric PUPs with HB (≤2 IU/dL endogenous FIX). Analyses described treatment patterns (on demand [OD] vs. prophylaxis) and prophylaxis type (started on vs. switched to prophylaxis). Kaplan-Meier analyses assessed the time to first spontaneous bleed, including median time to event and fitting models with predictors for treatment regimen and/or baseline age., Results: PUPs B-LONG enrolled 33 subjects. Baseline age did not influence the time to first spontaneous bleed for any rFIXFc regimen. Those who started on prophylaxis with rFIXFc (n = 11), compared with those treated OD (n = 22), had an extended time to first spontaneous bleed. Starting prophylaxis afforded a 93% reduced risk of first spontaneous bleed versus starting OD (hazard ratio [95% confidence interval]: 0.071 [0.009-0.592]) (p = .015)., Conclusion: rFIXFc prophylaxis, particularly starting early, reduced the risk of bleeding and delayed time to first spontaneous bleed compared with rFIXFc OD. Hence, initial treatment regimens impact bleed patterns in paediatric PUPs., (© 2024 Sanofi and The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Perclose ProGlide (PPG) Suture-Mediated Closure System™ is safe and can reduce time to hemostasis following procedures requiring arterial access., Aims: We aimed to compare PPG to figure of 8 suture in patients who underwent interventional catheter procedures requiring large bore venous access (LBVA) (≥13 French)., Methods: In this physician-initiated, randomized, single-center study [clinicaltrials.gov ID: NCT04632641], single-stick venous access was obtained under ultrasound guidance. Eligible patients were randomized 1:1, and 100 subjects received allocated treatment to either PPG (n = 47) or figure of 8 suture (n = 53). No femoral arterial access was used in any patient. Primary outcomes were time to achieve hemostasis (TTH) and time to ambulation (TTA). Secondary outcomes were time to discharge (TTD) and vascular-related complications and mortality. Wilcoxon rank-sum test was used to compare TTH, TTA, and TTD., Results: TTH (minutes) was significantly lower in PPG versus figure of 8 suture [median, (Q1, Q3)] [7 (2,10) vs. 11 (10,15) respectively, p < 0.001]. TTA (minutes) was significantly lower in PPG compared to figure of 8 suture [322 (246,452) vs. 403 (353, 633) respectively, p = 0.005]. TTD (minutes) was not significantly different between the PPG and figure of 8 suture arms [1257 (1081, 1544) vs. 1338 (1171,1435), p = 0.650]. There was no difference in minor bleeding or access site hematomas between both arms. No other vascular complications or mortality were reported., Conclusion: PPG use had lower TTH and TTA than figure of 8 suture in a population of patients receiving LBVA procedures. This may encourage same-day discharge in these patients., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Anticoagulants have long been fundamental in preventing and treating thromboembolic disorders, with a recent shift of focus towards direct oral anticoagulants, thanks to their ease of use, efficacy, and safety. Despite these advancements, bleeding complications remain a major concern with any anticoagulant, highlighting the need for safer drugs. Factor XI (FXI) inhibitors have emerged as promising agents in this regard, offering a novel approach by targeting upstream factors in the coagulation system. Phase II trials have shown encouraging outcomes, indicating a reduced bleeding risk compared to that associated with traditional anticoagulants, particularly in the context of cardiovascular disease management when combined with antiplatelet therapy. However, the variability in findings and limited efficacy data call for a cautious interpretation pending insights from phase III trials. These trials are essential for validating the potential of FXI inhibitors to balance bleeding risk reduction and maintain anticoagulant efficacy. This review explores the pharmacology, potential indications, clinical data, and future directions of FXI inhibitors, providing a perspective on their evolving role in anticoagulant therapy. It also provides a detailed analysis of data from published clinical trials on FXI inhibitors in various indications. Preliminary data from ongoing trials are also outlined. As the field moves forward, a cautiously optimistic outlook can be expected, focusing on comprehensive data from phase III trials to define the role of FXI inhibitors in various clinical scenarios.

Objective: Increasingly, medical schools integrate clinical skills into early didactic coursework. The Stop the Bleed® Campaign emphasizes prehospital hemorrhage control to reduce preventable deaths; however, this course overlooks team interactions. We assessed the impact of high-fidelity simulation during medical student orientation on identification and treatment of life-threatening hemorrhage in a team setting., Design: In this mixed method, prospective pre-, post-, and follow-up survey analysis assessing student knowledge and attitudes, student teams encountered a standardized patient in a prehospital environment with pulsatile bleeding from an extremity wound. Individual students completed surveys assessing previous experience, willingness and ability to assist bleeding person(s), and knowledge and attitudes about tourniquets. Postscenario, faculty preceptors made qualitative observations on teamwork., Setting: Medical student orientation at a tertiary care academic medical center with long-term follow-up., Participants: Medical students (N = 150)., Results: Ninety students (60%) completed both pre- and postsimulation questionnaires. Sixteen (17%) students had previous tourniquet training experience although none had applied a tourniquet outside of training. Postsimulation, students reported increased likelihood of providing treatment until additional help arrived (p = 0.035), improved ability to identify life-threatening hemorrhage (p < 0.001), and more favorable opinions about tourniquet use (p < 0.001) and potential for limb-salvage (p = 0.018). Long-term follow-up respondents (n = 34, 23%) reported increased ability to identify life-threatening hemorrhage (p = 0.010) and universal willingness to intervene until additional help arrived. Follow-up survey responses elicited themes in hemorrhage control including recognition of the importance of continuous pressure, appropriate use of tourniquets, a desire for repeated team training, and the recognition of clerkship rotations as an optimal setting for skill reinforcement. Preceptors noted variable team responses but uniformly endorsed the exercise., Conclusions: High-fidelity bleeding simulation during medical student orientation improved students' knowledge and attitudes about treating life-threatening hemorrhage and served as an introduction to team-based emergency care. Future studies should further explore team training and hemorrhage control education., (Copyright © 2024 Association of Program Directors in Surgery. All rights reserved.)

Thrombocytopenia is common in preterm neonates and can be associated with hemorrhage. Most platelet transfusions are prophylactic. Previously, higher platelet-count thresholds were recommended for neonates, but this recommendation has been questioned in recent studies. In the PlaNeT2 trial, mortality and serious bleeding were more frequent in neonates with the highest platelet-count threshold than in others. Following this trial, we changed our platelet transfusion practice by lowering the platelet-count threshold for prophylactic transfusion from 50,000 to 25,000/mm 3 . We conducted a before-after retrospective cohort study to quantify the frequency of platelet transfusions and assess the new protocol by analyzing death and serious hemorrhage events. This retrospective monocentric study included neonates born before 37 weeks of gestation with platelet count < 150,000/mm 3 during the 2 years preceding the new platelet transfusion protocol (high prophylactic transfusion threshold, 50,000/mm 3 ) and during the 2 years after the new platelet transfusion protocol (low prophylactic transfusion threshold, 25,000/mm 3 ). The primary outcome was the proportion of neonates receiving at least one platelet transfusion in both groups. We also compared the proportion of deaths and severe hemorrhage events. A total of 707 neonates with thrombocytopenia were identified. In the high-threshold group, 99/360 (27.5%) received at least one platelet transfusion as compared with 56/347 (16.1%) in the low-threshold group (p < 0.001). The groups did not differ in proportion of deaths or severe hemorrhage events., Conclusions: A reduced platelet-count threshold for transfusion allowed for a significant reduction in the number of platelet transfusions without increasing severe hemorrhage events., What Is Known: • A recent randomized trial suggested that restrictive platelet-count thresholds for platelet transfusion could be beneficial for preterm neonates., What Is New: • On lowering the platelet-count threshold for transfusion from 50,000 to 25,000/mm3, the number of transfusions significantly decreased without increasing severe hemorrhage events in a neonatal intensive care unit., (© 2024. The Author(s).)

Introduction: In Dar es Salaam, mortality from road traffic injuries is roughly double the global rate. Most civilians are transported to hospitals by laypeople. We examined the impact of a bleeding control course among taxi drivers., Methods: Before-after study; participants were trained in hemorrhage control and equipped with a first aid kit. Primary outcomes were perceived bleeding control knowledge, perceived ability to apply bleeding control skills, and intention to intervene. Surveys were administered before, after, and 3 mo after training. Data were measured on a 1-5 Likert scale., Results: Among 186 participants, knowledge increased from 1.70 (95% confidence interval [CI] 1.55-1.85) before training to 4.67 (95% CI 4.55-4.78) after training and was sustained at 3 mo 4.69 (95% CI 4.61-4.77). Ability to apply skills increased from 2.12 (95% CI 1.96-2.27) before training to 4.68 (95% CI 4.59-4.78) after training and was sustained at 3 mo 4.67 (95% CI 4.57-4.76). Intention to intervene increased from 2.69 (95% CI 2.47-2.92) before training to 4.66 (95% CI 4.55-4.76) after training and was sustained at 3 mo 4.57 (95% CI 4.48-4.67). 83 interventions occurred. Transport to health-care facilities occurred 58 times. Care was transferred to a doctor or nurse 39 times., Conclusions: This course increased participant's perceived bleeding control knowledge, ability to apply skills, and intention to intervene. Participants utilized skills in the field, transported the injured, and handed off care. This course should be evaluated globally in similar contexts., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although immunotherapy is expanding treatment options for cancer patients, the prognosis of advanced cancer remains poor, and these patients must contend with both cancers and cancer-related thrombotic events. In particular, immune checkpoint inhibitors are associated with an increased risk of atherosclerotic thrombotic events. Given the fundamental role of platelets in atherothrombosis, co-administration of antiplatelet agents is always indicated. Platelets are also involved in all steps of cancer progression. Classical antithrombotic drugs can cause inevitable hemorrhagic side effects due to blocking integrin β3 bidirectional signaling, which regulates simultaneously thrombosis and hemostasis. Meanwhile, many promising new targets are emerging with minimal bleeding risk and desirable anti-tumor effects. This review will focus on the issue of thrombosis during immune checkpoint inhibitor treatment and the role of platelet activation in cancer progression as well as explore the mechanisms by which novel antiplatelet therapies may exert both antithrombotic and antitumor effects without excessive bleeding risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: β1-blockers could improve clinical outcomes in patients with coronary artery disease by lowering the heart rate, blood pressure, and myocardial contractility. Moreover, recent studies have suggested that β1-blockers may also have the potential to reduce bleeding risk., Objectives: This study aimed to evaluate the association between β1-blockers and bleeding risk in the patients prescribed with potent dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI)., Methods: Patients with ACS or undergoing PCI treated by DAPT of ticagrelor and aspirin were consecutively recruited. Follow-up for all eligible patients was conducted for 1 year. Major bleeding outcomes were defined as events that were type ≥2 based on the Bleeding Academic Research Consortium (BARC) criteria., Results: A total of 1,113 eligible ticagrelor-treated patients were recruited. During the 1-year follow-up interval, 142 (12.6%) patients experienced BARC ≥2 bleedings including 23 patients (2.1%) suffering BARC ≥3 bleedings, with the most common site of bleeding located in the gastrointestinal tract. β1-blockers treatment was associated with a lower risk of BARC ≥2 bleedings (11.2% vs. 23.3%, adjusted HR: 0.42, 95% CI: 0.28-0.62, P < 0.01). Moreover, metoprolol (11.1% vs. 23.3%, adjusted HR: 0.56, 95% CI: 0.37-0.83, P < 0.01) and bisoprolol (11.3% vs. 23.3%, adjusted HR: 0.56, 95% CI: 0.33-0.96, P = 0.04) had similar effects on the reduction of bleeding risk., Conclusion: β1-blockers might be beneficial for the reduction of bleeding risk in potent dual antiplatelet therapy patients with ACS or undergoing PCI., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Anticoagulation is common in patients undergoing routine musculoskeletal interventional maneuvers. Previous retrospective studies have established the safety of continuing anticoagulation with novel oral anticoagulants (NOACs) when performing this kind of interventions. Indeed, ultrasound (US)-guided interventional maneuvers have shown a superior safety profile compared to blind anatomical maneuvers. To evaluate prospectively the periprocedural bleeding events in NOAC-anticoagulated patients undergoing interventional articular or periarticular procedures. Consecutive patients diagnosed with inflammatory or degenerative rheumatologic pathology requiring interventional maneuvers were prospectively recruited. Group 1 was treated with NOACs, group 2 was treated with vitamin K antagonists, and group 3 was not anticoagulated. Prior to the international maneuver, NOAC therapy was continuously administered, in regimens dictated by the underlying anticoagulation indication. Demographics, comorbidities, laboratory parameters, locally administered medication (corticosteroids or viscosupplementation), interventional maneuver location, needle size, and local bleeding events were recorded. Post-procedural control was performed at 30 min, 48 h, and 7 days. No articular/periarticular bleeding event occurred in patients treated with NOACs, regardless of their type and dosage, locally administered medication, needle size, location, and number of interventions per individual. Several patients in all groups developed small superficial ecchymoses at the injection site. Our results suggest that NOACs are safe to be used in a continuous regimen prior to US-guided injections, even as dual antithrombotic therapy (in combination with aspirin). The use of lower gauge needles, chosen for viscosupplementation therapy, was not burdened with adverse effects on the procedural outcome. Key Points • Currently, no prospective studies have been performed to establish the safety of continuous NOAC anticoagulation when performing routine intra- or periarticular interventional maneuvers. • The study offers an extensive view on a wide spectrum of intra- and periarticular interventional maneuvers including anatomic targets and needle sizes that were not previously assessed. • The study offers a perspective into performing repetitive maneuvers in the same patient, both over a short time and at longer intervals. • The zero periprocedural bleeding risk observed in our study may reassure practitioners and suggest that US-guided interventional therapeutic interventions are safe in patients treated with a continuous regimen of different NOACs., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: MynxGrip is a non-suture, balloon catheter- and extravascular sealant-based vascular closure device designed to help hemostasis after an arterial puncture. This study evaluated the efficacy and safety of MynxGrip versus manual compression for femoral artery access closure in patients undergoing diagnostic or interventional procedures., Methods: The PANDA multicenter, parallel-group, open-label, randomized controlled trial enrolled patients undergoing a diagnostic or interventional procedure through femoral artery access between April 2019 and September 2020 at six centers in China. The participants were randomized 2:1 to the MynxGrip group and the manual compression group. Time to hemostasis and incidence of severe complications were the primary efficacy and safety endpoints, respectively., Results: A total of 304 consecutive participants were included. The baseline characteristics were similarly distributed in the MynxGrip ( n  = 203) versus manual compression ( n  = 101) groups. Compared with the manual compression group, the median time to hemostasis and time to ambulation were significantly shorter (3.0 (interquartile range: 2.0, 4.0) vs 18.0 (11.0, 22.0) min, and 479.0 (275.0, 932.0) vs 1410.3 (1121.0, 1476.0) min, respectively; both p  = 0.0001) in the MynxGrip group, with similar procedural success rate, and without severe complications in either group. The incidence of device-related adverse events was 11.8% in the MynxGrip group, most possibly or definitely unrelated., Conclusions: Compared with manual compression, the MynxGrip vascular closure device significantly shortens the times to hemostasis and ambulation without severe complications after diagnostic or interventional procedures through the femoral artery access., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The development of efficient hemostatic materials is crucial for achieving rapid hemorrhage control and effective wound healing. Inorganic polyphosphate (polyP) is recognized as an effective modulator of the blood coagulation process. However, the specific effect of polyP chain length on coagulation is not yet fully understood. Furthermore, calcium ions (Ca 2+ ) are essential for the coagulation process, promoting multiple enzyme-catalyzed reactions within the coagulation cascade. Hence, calcium ion-coupled polyphosphate powders with three different degrees of polymerization (CaPP- n , n = 20, 50, and 1500) are synthesized by an ion-exchange reaction. CaPP exhibits a crystalline phase at a low polymerization degree and transitions to an amorphous phase as the polymerization degree increases. Notably, the addition of Ca 2+ enhances the wettability of polyP, and CaPP promotes hemostasis, with varying degrees of effectiveness related to chain length. CaPP-50 exhibits the most promising hemostatic performance, with the lowest blood clotting index (BCI, 12.1 ± 0.7%) and the shortest clotting time (302.0 ± 10.5 s). By combining Ca 2+ with polyP of medium-chain length, CaPP-50 demonstrates an enhanced ability to accelerate the adhesion and activation of blood cells, initiate the intrinsic coagulation cascade, and form a stable blood clot, outperforming both CaPP-20 and CaPP-1500. The hemostatic efficacy of CaPP-50 is further validated using rat liver bleeding and femoral artery puncture models. CaPP-50 is proven to possess hemostatic properties comparable to those of commercial calcium-based zeolite hemostatic powder and superior to kaolin. In addition, CaPP-50 exhibits excellent biocompatibility and long-term storage stability. These results suggest that CaPP-50 has significant clinical and commercial potential as an active inorganic hemostatic agent for rapid control of bleeding.

Background: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach., Aim: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis., Methods: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions., Primary Endpoint: the successful completion of hemodialysis without clotting., Secondary Outcomes: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions., Results: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed., Conclusions: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding.

Background/purpose: Double-filtration plasmapheresis (DFPP) can be used to remove circulating pathogenic molecules. By reclaiming filtered albumin, DFPP reduces the need for albumin and plasma replacement. Large proteins, such as fibrinogen, are removed. Our institution adopts a DFPP treatment protocol consisting of active surveillance of coagulation profiles and prophylactic supplementation of blood products containing fibrinogen. This study aims to investigate the effects of consecutive DFPP treatments on serial coagulation profiles and the risk of bleeding under this protocol., Methods: Serial laboratory data and bleeding events at a single tertiary medical center were prospectively collected. Prophylactic transfusion of cryoprecipitate or fresh frozen plasma (FFP) was instituted if significant coagulopathy or a clinically evident bleeding event was observed., Results: After the first treatment session, plasma fibrinogen levels decreased from 332 ± 106 mg/dL to 96 ± 44 mg/dL in the 37 study patients. In the following sessions, plasma fibrinogen levels were maintained at around 100 mg/dL under prophylactic transfusion. No major bleeding events were recorded, but five (14%) patients experienced minor bleeding., Conclusion: DFPP treatment might be performed safely along with active monitoring of coagulation profiles and prophylactic transfusion of cryoprecipitate or FFP., Competing Interests: Declaration of competing interest All the authors declared no competing interests., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Radial access is the default approach in interventional cardiology. The Axiostat® surgical hemostatic dressing, using chitosan as its active component, has demonstrated potential in accelerating blood clotting. This study aims to assess the efficacy and the safety of the Axiostat® dressing in achieving hemostasis in patients undergoing transradial coronary angioplasty (TRCA)., Methods: This prospective, single-center observational study, conducted in 2022, enrolled consecutive patients undergoing TRCA, with a target of 150 participants. The primary outcome was the success rate of radial artery hemostasis at 120 min, without bleeding necessitating immediate re-compression. The secondary outcome included Axiostat® performance at 24 h and 30 days Postprocedure., Results: The study was terminated prematurely for ethical and patient safety reasons, after inclusion of 41 consecutive TRCA patients due to an unexpectedly high radial artery thrombosis rate (19.5%, n = 8/41) observed 24 h Postprocedure. The success rate of radial hemostasis with the Axiostat® dressing was 78.0%. Procedural details and patient characteristics were comparable between successful Axiostat® removal and device failure cases., Conclusion: The use of the Axiostat® dressing to achieve hemostasis after TRCA is effective but is associated with an unexpectedly high incidence of radial thrombosis. Our results should encourage caution in the future evaluation and use of this device for radial artery compression following TRCA., (© 2024 Wiley Periodicals LLC.)

Abstract: Tranexamic acid is an inexpensive antifibrinolytic treatment that reduces morbidity and mortality in civilian and military trauma patients. It must be administered within 3 hours of the injury, and its efficacy is greater the earlier it is given. It is already used preventively in the civilian environment in a number of indications to reduce bleeding and bleeding-related mortality. We wondered about the potential benefits of preventive oral administration of tranexamic acid prior to an assault for military personnel with a potential risk of injury., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Background: Once-weekly efanesoctocog alfa provides high sustained factor VIII activity with superior bleeding prevention as compared with prestudy factor VIII prophylaxis in previously treated patients 12 years of age or older with severe hemophilia A. Data on outcomes of efanesoctocog alfa treatment in children younger than 12 years of age with severe hemophilia A are limited., Methods: We conducted a phase 3, open-label study involving previously treated patients younger than 12 years of age with severe hemophilia A. Patients received prophylaxis with once-weekly efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks. The primary end point was the occurrence of factor VIII inhibitors (neutralizing antibodies against factor VIII). Secondary end points included annualized rates of treated bleeding episodes, bleeding treatment, safety, and pharmacokinetics., Results: A total of 74 male patients were enrolled (38 with an age of <6 years and 36 with an age of 6 to <12 years). No factor VIII inhibitors developed. Most adverse events were nonserious. No serious adverse events that were assessed by the investigator as being related to efanesoctocog alfa were reported. In the 73 patients treated according to the protocol, the median and model-based mean annualized bleeding rates were 0.00 (interquartile range, 0.00 to 1.02) and 0.61 (95% confidence interval, 0.42 to 0.90), respectively. A total of 47 patients (64%) had no treated bleeding episodes, 65 (88%) had no spontaneous bleeding episodes, and 61 (82%) had no episodes of bleeding into joints. A total of 41 of 43 bleeding episodes (95%) resolved with one injection of efanesoctocog alfa. Mean factor VIII activity at steady state was more than 40 IU per deciliter for 3 days and more than 10 IU per deciliter for almost 7 days after dose administration. The geometric mean terminal half-life was 40.0 hours., Conclusions: In children with severe hemophilia A, once-weekly prophylaxis with efanesoctocog alfa provided high sustained factor VIII activity in the normal to near-normal range (>40 IU per deciliter) for 3 days and more than 10 IU per deciliter for almost 7 days after administration, leading to effective bleeding prevention. Efanesoctocog alfa was associated with mainly nonserious adverse events. (Funded by Sanofi and Sobi; XTEND-Kids ClinicalTrials.gov number, NCT04759131.)., (Copyright © 2024 Massachusetts Medical Society.)

Chronic hemodialysis patients exhibit an excessive cardiovascular risk and a marked increase in both thromboembolism and bleeding episodes. Factor XI inhibition may provide anticoagulation, with a low risk of bleeding, and several factor XI inhibitors, including fesomersen, an antisense oligonucleotide, are under development. Recently, a phase 2 study of fesomersen showed a good safety profile in chronic hemodialysis patients and suggested that clotting rates of the arteriovenous fistula and the dialysis circuit are lower., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

This work aimed at formulating a trilaminate dressing loaded with tranexamic acid. It consisted of a layer of 3 % sodium hyaluronate to initiate hemostasis. It was followed by a mixed porous layer of 5 % polyvinyl alcohol and 2 % kappa-carrageenan. This layer acted as a drug reservoir that controlled its release. The third layer was 5 % ethyl cellulose backing layer for unidirectional release of tranexamic acid towards the wound. The 3 layers were physically crosslinked by hydrogen bonding as confirmed by Infrared spectroscopy. Swelling and release studies were performed, and results proposed that increasing number of layers decreased swelling properties and sustained release of tranexamic acid for 8 h. In vitro blood coagulation study was performed using human blood and showed that the dressing significantly decreased coagulation time by 70.5 % compared to the negative control. In vivo hemostatic activity was evaluated using tail amputation model in Wistar rats. Statistical analysis showed the dressing could stop bleeding in a punctured artery of the rat tail faster than the negative control by 59 %. Cranial bone defect model in New Zealand rabbits was performed to check for bone hemostasis and showed significant decrease in the hemostatic time by 80 % compared to the control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence-based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes., Study Design and Methods: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581)., Results: In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty-seven outcomes were reported with a mean of 11 (min-max. 4-32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage., Conclusion: There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion., (© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Traumatic hemorrhage is a prevalent cause of death nationally, with >50% of civilian deaths estimated to be preventable with more timely intervention. This study investigated the efficacy of training large and diverse audiences in bleeding control methods including tourniquets in community health fair settings., Methods: A booth was utilized for bleeding control training at community health fairs via direct demonstrations of pressure, wound packing, and commercial and improvised tourniquet application followed by hands-on practice. Participants self-rated their perceived abilities while instructors rated the participant competency., Results: 117 community members participated during two fairs, though not every person completed every portion of the training. Average age was 33 (range 6-82) and the majority were female (65.0%). There was no difference in self-perceived skill compared to trainer grading of participant's ability to identify life-threatening bleeding (112 (97.4%) vs 106 (97.2%); P = 1), apply pressure (113 (98.3%) vs 106 (97.2%); P = .68), and pack a wound (102 (88.7%) vs 92 (84.4%); P = .43). No difference in difficulty was noted in placing commercial vs improvised tourniquets (16 (43%) vs 14 (45%); P = .87). However, participants were overconfident in their ability to place tourniquets compared to trainer grading, respectively (112 (98.2%) vs 100 (91.7%; P = .03))., Discussion: Community fair classes provide opportunities to train large and diverse audiences in bleeding control techniques. However, participants overestimated their ability to appropriately apply tourniquets. Further investigation is needed into best educational approaches to optimize the impact of bleeding control kits that have been distributed in multiple states., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Hemorrhage is the leading cause of preventable death after trauma. In high-income countries first responders are trained in hemorrhage control techniques but this is not the case for developing countries like Guatemala. We present a low-cost training model for tourniquet application using a combination of virtual and physical components., Methods: The training program includes a mobile application with didactic materials, videos and a gamified virtual reality environment for learning. Additionally, a physical training model of a bleeding lower extremity is developed allowing learners to practice tourniquet application using inexpensive and accessible materials. Validation of the simulator occurred through content and construct validation. Content validation involved subjective assessments by novices and experts, construct validation compared pre-training novices with experts. Training validation compared pre and post training novices for improvement., Results: Our findings indicate that users found the simulator useful, realistic, and satisfactory. We found significant differences in tourniquet application skills between pre-training novices and experts. When comparing pre- and post-training novices, we found a significantly lower bleeding control time between the groups., Conclusion: This study suggests that this training approach can enhance access to life-saving skills for prehospital personnel. The inclusion of self-assessment components enables self-regulated learning and reduces the need for continuous instructor presence. Future improvements involve refining the tourniquet model, validating it with first-responder end users, and expanding the training program to include other skills., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Since the first documented use of a tourniquet in 1674, the popularity of tourniquets has waxed and waned. During recent wars and more recently in Emergency Medical Services systems, the tourniquet has been proven to be a valuable tool in the treatment of life-threatening hemorrhage. However, tourniquet use is not without risk, and several studies have demonstrated adverse events and morbidity associated with tourniquet use in the prehospital setting, particularly when left in place for more than 2 h. Consequently, the US military's Committee on Tactical Combat Casualty Care has recommended guidelines for prehospital tourniquet conversion to reduce the risk of adverse events associated with tourniquets once the initial hemorrhage has been controlled. Emergency Medical Services systems that operate in rural, frontier, and austere environments, especially those with transport times to definitive care that routinely exceed 2 h, may consider implementing similar tourniquet conversion guidelines.

The rapid absorption of water from the blood to concentrate erythrocytes and platelets, thus triggering quick closure, is important for hemostasis. Herein, expansion-clotting chitosan fabrics are designed and fabricated by ring spinning of polylactic acid (PLA) filaments as the core layer and highly hydrophilic carboxyethyl chitosan (CECS) fibers as the sheath layer, and subsequent knitting of obtained PLA@CECS core spun yarns. Due to the unidirectional fast-absorption capacity of CECS fibers, the chitosan fabrics can achieve erythrocytes and platelets aggregate quickly by concentrating blood, thus promoting the formation of blood clots. Furthermore, the loop structure of coils formed in the knitted fabric can help them to expand by absorbing water to close their pores, providing effective sealing for bleeding. Besides, They have enough mechanical properties, anti-penetrating ability, and good tissue-adhesion ability in wet conditions, which can form a physical barrier to resist blood pressure during hemostasis and prevent them from falling off the wound, thus enhancing hemostasis synergistically. Therefore, the fabrics exhibit superior hemostatic performance in the rabbit liver, spleen, and femoral artery puncture injury model compared to the gauze group. This chitosan fabric is a promising hemostatic material for hemorrhage control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: External bleeding is the leading cause of preventable trauma-related death. In certain circumstances, tourniquet application over clothing may be necessary. Therefore, the aim of this study was to assess the effectiveness of tourniquets over different clothing setups., Methods: Three windlass tourniquets (CAT, SAMXT, SOFTT-W) were applied over nine different clothing setups and without clothing on the Hapmed™ Tourniquet Trainer. We compared each tourniquet in each clothing setup to the tourniquet trainer that was not dressed, and we compared the three tourniquets within each clothing setup concerning blood loss, applied pressure and application time. Regression analysis of the effect of thickness, mean weight, mean deformation, application time, and applied pressure on blood loss was performed., Results: Although blood loss was significantly greater in the CAT and SAMXT tourniquets when they were applied over leather motorcycle trousers, the overall findings showed that the clothing setups significantly reduced or did not affect blood loss. The mean blood loss was the lowest with CAT and the highest with SOFTT-W. The measured mean pressures were lower than 180 mmHg in four out of nine clothing setups with SOFTT-W, but CAT and SAMXT always exceeded this threshold. CAT had the fastest application time. Blood loss was significantly influenced by applied pressure and application time but was influenced to a far lesser degree by clothing parameters., Conclusion: The effects of the clothing setups were of little clinical relevance, except for leather motorcycle trousers. The effects of rugged protective equipment, e.g., hazard suits, are conceivable and need to be tested for specific garments with the tourniquet intended for use. No clothing parameter for predicting tourniquet effectiveness could be identified., (© 2024. The Author(s).)

Abstract: Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary end point was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary end points included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor, n = 19; noninhibitor, n = 46) were eligible for ABR analyses. Observed median ABRs were 6.5 (interquartile range [IQR], 2.2-19.6)/4.4 (IQR, 2.2-8.7) with BPA/CFC prophylaxis vs 0.0 (IQR, 0.0-0.0)/0.0 (IQR, 0.0-2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = .0021) and 46.4% (P = .0598) vs BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced 0 treated bleeds with fitusiran vs 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events vs BPA/CFC prophylaxis in PwHA/B, with or without inhibitors, and reported adverse events were generally consistent with previously identified risks of fitusiran. This trial was registered at www.ClinicalTrials.gov as #NCT03549871., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Myocardial infarction (MI) as a consequence of atherosclerosis-associated acute thrombosis is a leading cause of death and disability globally. Antiplatelet and anticoagulant drugs are standard therapies in preventing and treating MI. However, all clinically used drugs are associated with bleeding complications, which ultimately limits their use in patients with a high risk of bleeding. We have developed a new recombinant drug, targ-HSA-TAP, that combines targeting and specific inhibition of activated platelets as well as anticoagulation. This drug is designed and tested for a prolonged circulating half-life, enabling unique thromboprophylaxis without bleeding complications. Methods: Targ-HSA-TAP combines a single-chain antibody (scFv) that targets activated glycoprotein IIb/IIIa on activated platelets, human serum albumin (HSA) for prolonged circulation, and tick anticoagulant peptide (TAP) for coagulation FX inhibition. A non-binding scFv is employed as a non-targeting control (non-targ-HSA-TAP). Its efficacy was investigated in vivo using murine models of acute thrombosis and cardiac ischemia-reperfusion (I/R) injury. Results: Our experiments confirmed the targeting specificity of targ-HSA-TAP to activated platelets and demonstrated effective prevention of platelet aggregation and thrombus formation, as well as FXa inhibition in vitro . Thromboprophylactic administration of targ-HSA-TAP subcutaneously in mice prevented occlusion of the carotid artery after ferric chloride injury as compared to non-targ-HSA-TAP and PBS-control treated mice. By comparing the therapeutic outcomes between targ-TAP and targ-HSA-TAP, we demonstrate the significant improvements brought by the HSA fusion in extending the drug's half-life and enhancing its therapeutic window for up to 16 h post-administration. Importantly, tail bleeding time was not prolonged with targ-HSA-TAP in contrast to the clinically used anticoagulant enoxaparin. Furthermore, in a murine model of cardiac I/R injury, mice administered targ-HSA-TAP 10 h before injury demonstrated preserved cardiac function, with significantly higher ejection fraction and fractional shortening, as compared to the non-targ-HSA-TAP and PBS control groups. Advanced strain analysis revealed reduced myocardial deformation and histology confirmed a reduced infarct size in targ-HSA-TAP treated mice compared to control groups. Conclusion: The inclusion of HSA represents a significant advancement in the design of targeted therapeutic agents for thromboprophylaxis. Our activated platelet-targeted targ-HSA-TAP is a highly effective antithrombotic drug with both anticoagulant and antiplatelet effects while retaining normal hemostasis. The long half-life of targ-HSA-TAP provides the unique opportunity to use this antithrombotic drug for more effective, long-lasting and safer anti-thrombotic prophylaxis. In cases where MI occurs, this prophylactic strategy reduces thrombus burden and effectively reduces cardiac I/R injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI)., Objectives: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI., Methods: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month., Results: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions., Conclusions: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111)., Competing Interests: Funding Support and Author Disclosures This study was funded by Abbott Medical Japan. Dr Natsuaki has received honoraria from Abbott Medical Japan, Daiichi-Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr Watanabe has received personal fees from Abbott Medical Japan during the conduct of the study as well as personal fees from Daiichi-Sankyo, Kowa, Abiomed, Bayer, Pfizer, Bristol Myers Squibb, and Otsuka outside the submitted work. Dr Morimoto has received lecturer fees from AstraZeneca, Bristol Myers Squibb, Daiichi-Sankyo, Japan Lifeline, Kowa, Pfizer, and Tsumura; has received manuscript fees from Bristol Myers Squibb and Pfizer; and has served on the Advisory Boards for Novartis and Teijin. Dr Suwa has received personal fees from Abbott Medical Japan and Daiichi-Sankyo outside the submitted work. Dr Kimura has received grants from Abbott Medical Japan and Boston Scientific; and has served on the Advisory Boards of Abbott Medical Japan and Terumo Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated promising results., Objectives: We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis., Design and Setting: Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil., Methods: The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds., Results: Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: -1.58; 95% confidence interval -2.50, -0.66, P = 0.0008; I2 = 68.4%, P = 0.0031)., Conclusion: Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results., Systematic Review Registration: CRD42021278726, https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=278726.

Introduction: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided., Methods: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones., Results: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best., Conclusion: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis., (© 2024 Wiley Periodicals LLC.)

Introduction: In the United States, all 50 states and the District of Columbia have Good Samaritan Laws (GSLs). Designed to encourage bystanders to aid at the scene of an emergency, GSLs generally limit the risk of civil tort liability if the care is rendered in good faith. Nation-wide, a leading cause of preventable death is uncontrolled external hemorrhage. Public bleeding control initiatives aim to train the public to recognize life-threatening external bleeding, perform life-sustaining interventions (including direct pressure, tourniquet application, and wound packing), and to promote access to bleeding control equipment to ensure a rapid response from bystanders., Methods: This study sought to identify the GSLs in each state and the District of Columbia to identify what type of responder is covered by the law (eg, all laypersons, only trained individuals, or only licensed health care providers) and if bleeding control is explicitly included or excluded in their Good Samaritan coverage., Results: Good Samaritan Laws providing civil liability qualified immunity were identified in all 50 states and the District of Columbia. One state, Oklahoma, specifically includes bleeding control in its GSLs. Six states - Connecticut, Illinois, Kansas, Kentucky, Michigan, and Missouri - have laws that define those covered under Good Samaritan immunity, generally limiting protection to individuals trained in a standard first aid or resuscitation course or health care clinicians. No state explicitly excludes bleeding control from their GSLs, and one state expressly includes it., Conclusion: Nation-wide across the United States, most states have broad bystander coverage within GSLs for emergency medical conditions of all types, including bleeding emergencies, and no state explicitly excludes bleeding control interventions. Some states restrict coverage to those health care personnel or bystanders who have completed a specific training program. Opportunity exists for additional research into those states whose GSLs may not be inclusive of bleeding control interventions.

Hemorrhage is the second leading cause of death in patients under 46 years of age in the United States. Cessation of hemorrhage prevents hemorrhagic shock and tissue hypoxia. Controlling the bleed via direct pressure or tourniquet is often the first line of defense, but long-term care requires staples, hemostatic agents, or sealants that seal the vessel and restore blood flow. Here, we compare a new photocurable extracellular matrix sealant (pcECM) with low, medium, and high crosslink density formulations to a commercially available fibrin-based sealant, TISSEEL®. pcECM has potential uses in surgical and remote settings due to room temperature storage conditions and fast preparation time. Here, we determine if pcECM sealant can stop venous hemorrhage in a murine model, adhere to the wound site in vivo throughout the wound-healing process, and has the mechanical properties necessary for stopping hemorrhage. Adjusting pcECM crosslinking density significantly affected viscosity, swelling, burst strength, tensile strength, and elasticity of the sealant. 3-Dimensional ultrasound volume segmentations showed pcECM degrades to 17 ± 8% of its initial implant volume by day 28. Initially, local hemodynamic changes were observed, but returned close to baseline levels by day 28. Acute inflammation was observed near the puncture site in pcECM implanted mice, and we observed inflammatory markers at the 14-day explant for both sealants. pcECM and fibrin sealant successfully sealed the vessel in all cases, and consistently degraded over 14-28 days. pcECM is a durable sealant with tunable mechanical properties and possible uses in hemorrhage control and other surgical procedures., (© 2024 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

Objective: We hypothesized that medical students would be empowered by hemorrhage-control training and would support efforts to include Stop the Bleed® (STB) in medical education., Design: This is a multi-institution survey study. Surveys were administered immediately following and 6 months after the course., Setting: This study took place at the Association of American Medical Colleges-accredited medical schools in the United States., Participants: Participants were first-year medical students at participating institutions. A total of 442 students completed post-course surveys, and 213 students (48.2 percent) also completed 6-month follow-up surveys., Intervention: An 1-hour, in-person STB course., Main Outcomes Measures: Student empowerment was measured by Likert-scale scoring, 1 (Strongly Disagree) to 5 (Strongly Agree). The usage of hemorrhage-control skills was also measured., Results: A total of 419 students (95.9 percent) affirmed that the course taught the basics of bleeding control, and 169 (79.3 percent) responded positively at follow-up, with a significant decrease in Likert response (4.65, 3.87, p < 0.001). Four hundred and twenty-three students (97.0 percent) affirmed that they would apply bleeding control skills to a patient, and 192 (90.1 percent) responded positively at follow-up (4.61, 4.19, p < 0.001). Three hundred and sixty-one students (82.8 percent) believed that they were able to save a life, and 109 (51.2 percent) responded positively at follow-up (4.14, 3.56, p < 0.001). Four hundred and twenty-five students (97.0 percent) would recommend the course to another medical student, and 196 (92.0 percent) responded positively at follow-up (4.68, 4.31, p < 0.001). Six students (2.8 percent) used skills on live patients, with success in five of the six instances., Conclusions: Medical students were empowered by STB and have used hemorrhage-control skills on live victims. Medical students support efforts to include STB in medical education.

Introduction: Nurses' preparedness to provide hemorrhage control aid outside of the patient care setting has not been thoroughly evaluated. We evaluated nurses' preparedness to provide hemorrhage control in the prehospital setting after a proof-of-concept training event., Methods: We performed a secondary analysis of evaluations from a voluntary hemorrhage control training offered to a group of experienced nurses. Education was provided by a nurse certified in Stop the Bleed training and using the Basic Bleeding Control 2.0 materials. The training lasted approximately 1 hour and included a didactic portion followed by hands-on practice with task trainer legs. Participants were surveyed after training to assess their preparedness to provide hemorrhage control aid using a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree); comments and feedback were also requested. Mean (SD) was used to analyze Likert scale data. Content analysis was performed to identify common themes in qualitative data., Results: Forty-five experienced nurses participated in the voluntary training. Nursing experience included obstetrics, pediatrics, critical care, acute care, community health, and psychiatric/mental health. Only 39% of participants reported having previously completed a similar course. After training completion, participants reported an increase in their preparedness to provide hemorrhage control aid (mean 3.47 [SD = 1.40] vs mean 4.8 SD [.04], P < .01). Major themes identified included wanting to feel prepared to help others, refreshing skills, and knowing how to respond in an emergency., Discussion: Regardless of background and experience, nurses may benefit from more advanced hemorrhage control education to prepare them to provide aid in prehospital emergency settings., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

A community that is trained to respond to life-threatening bleeding can reduce the risk of death from trauma and violence. Stop The Bleed is a nationally recognized, free, 1-hour bleeding control training designed for laypersons. Implementing a campuswide Stop the Bleed initiative can be daunting, yet vital to creating a safe, prepared campus. Guidance is offered by faculty, staff, and students from a Stop the Bleed initiative at a public university in the southern United States. This guide provides real-life examples and recommendations based on experience. Utilization of population health nursing students is a fundamental component of success., (© 2024 Wiley Periodicals LLC.)

Hemorrhage is the leading cause of trauma death, and innovation in hemostatic technology is important. The strongly hydrophobic carbon nanofiber (CNF) coating has previously been shown to have excellent hemostatic properties. However, the understanding of how CNF coating guides the coagulation cascade and the biosafety of CNF as hemostatic agents has yet to be explored. Here, our thrombin generation assay investigation showed that CNF induced fast blood coagulation via factor (F) XII activation of the intrinsic pathway. We further performed studies of a rat vein injury and demonstrated that the CNF gauze enabled a substantial reduction of blood loss compared to both the plain gauze and kaolin-imbued gauze (QuikClot). Analysis of blood samples from the model revealed no acute toxicity from the CNF gauze, with no detectable CNF deposition in any organ, suggesting that the immobilization of CNF on our gauze prevented the infiltration of CNF into the bloodstream. Direct injection of CNF into the rat vein was also investigated and found not to elicit overt acute toxicity or affect animal survival or behavior. Finally, toxicity assays with primary keratinocytes revealed minimal toxicity responses to CNF. Our studies thus supported the safety and efficacy of the CNF hemostatic gauze, highlighting its potential as a promising approach in the field of hemostatic control.

Large bore accesses refer to accesses with a diameter of 10 French or greater and are necessary for various medical devices, including those used in transcatheter aortic valve replacement, endovascular aneurysm repair stent-grafts, and percutaneous mechanical support devices. Notably, the utilization of these devices via femoral access is steadily increasing due to advancements in technology and implantation techniques, which are expanding the pool of patients suitable for percutaneous procedures. However, procedures involving large bore devices carry a high risk of bleeding and vascular complications (VCs), impacting both morbidity and long-term mortality. In this review article, we will first discuss the incidence, determinants, and prognostic impact of VCs in patients undergoing large bore access procedures. Subsequently, we will explore the strategies developed in recent years to minimize VCs, including techniques for optimizing vascular puncture through femoral cannulation, such as the use of echo-guided access cannulation and fluoroscopic guidance. Additionally, we will evaluate existing vascular closure devices designed for large bore devices. Finally, we will consider new pharmacological strategies aimed at reducing the risk of periprocedural access-related bleeding., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background:  For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and for bleeding in association with the direct factor Xa inhibitors rivaroxaban or apixaban, the modified recombinant FXa protein andexanet is available for reversal. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures., Methods:  An interdisciplinary group of experienced experts in the fields of angiology, hematology, internal medicine, clinical pharmacology, laboratory medicine, transfusion medicine, anesthesiology, intensive care, and hemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence., Results:  Reversal of oral anticoagulants should be considered for severe bleeding in the following situations: (1) life-threatening bleeding or refractory hemorrhagic shock, (2) intracerebral bleeding, or (3) endoscopically unstoppable gastrointestinal bleeding. After successful hemostasis, anticoagulation (e.g., direct oral anticoagulant, vitamin K antagonist, and heparin) should be resumed promptly, taking into account individual bleeding and thromboembolic risk., Discussion:  This article aims to facilitate the management of patients with andexanet by all medical disciplines involved, thereby ensuring optimal care of patients during bleeding episodes., Competing Interests: Dieses Manuskript fasst die wesentlichen Diskussionspunkte eines interdisziplinären Expertentreffens im August 2022 mit Vertreter*innen aus der Angiologie, Hämatologie, Innerer Medizin, klinischer Pharmakologie, Labormedizin, Transfusionsmedizin Intensivmedizin und Hämostaseologie zusammen, in dem die Bedeutung und die möglichen Einsatzgebiete von spezifischen Antidots zur Antagonisierung der neuen/direkten orale Antikoagulantien (DOAK) bei schweren und lebensbedrohlichen Blutungen diskutiert und herausgearbeitet wurde. Dieses Expertentreffen wurde durch die Fa. AstraZeneca finanziell unterstützt., (Thieme. All rights reserved.)

Purpose: To evaluate the effectiveness of track embolization using gelatin sponge slurry in percutaneous ultrasound (US)-guided liver biopsy., Materials and Methods: Among the 543 patients who underwent percutaneous US-guided liver biopsies between September 2018 and August 2021, 338 who did not undergo track embolization and 105 who underwent track embolization were included in the analysis. All procedures were performed with 18-gauge coaxial core biopsy needles. Patients' laboratory data were reviewed. Patients in both groups were subdivided into the following 2 groups: (a) those with targeted biopsy for a focal liver lesion and (b) those with nontargeted biopsy for a liver parenchyma. Moreover, postbiopsy events, such as transfusion and transarterial embolization, were assessed. To minimize selection bias, propensity score matching (PSM) was performed., Results: After PSM, all factors that could affect bleeding risk were well-matched and well-balanced between the 2 groups (P > .474). In the non-track embolization group, 17 (16.2%) patients experienced major or minor bleeding-related adverse events (AEs). In contrast, in the track embolization group, only 5 (4.8%) patients experienced major or minor bleeding-related AEs, which was significantly lower than that in the non-track embolization group (P = .007). All 5 (4.8%) cases of major bleeding-related AEs were observed in the non-track embolization group (P = .024)., Conclusions: In this study, a retrospective analysis was performed using PSM for percutaneous US-guided liver biopsy. Track embolization using gelatin sponge slurry is significantly superior in the prevention of bleeding-related AEs after US-guided liver biopsy., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: While the principles of damage control surgery - rapid hemorrhage and contamination control with correction of physiologic derangements followed by delayed definitive reconstruction - have remained consistent, forms of damage control intervention have evolved and proliferated dramatically. This review aims to provide a historic perspective of the early trends of damage control surgery as well as an updated understanding of its current state and future trends., Recent Findings: Physiologically depleted patients in shock due to both traumatic and nontraumatic causes are often treated with damage control laparotomy and surgical principles. Damage control surgery has also been shown to be safe and effective in thoracic and orthopedic injuries. Damage control resuscitation is used in conjunction with surgical source control to restore patient physiology and prevent further collapse. The overuse of damage control laparotomy, however, is associated with increased morbidity and complications. With advancing technology, catheter- and stent-based endovascular modalities are playing a larger role in the resuscitation and definitive care of patients., Summary: Optimal outcome in the care of the most severely injured patients requires judicious use of damage control surgery supplemented by advancements in resuscitation and surgical adjuncts., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The long half-life and subcutaneous mode of administration makes emicizumab a compelling treatment option for bleeding prophylaxis. There is still limited real-world data on its use and management considerations, especially during surgical procedures. The objective of the study is to describe the real-world experience of emicizumab in a cohort of adult and paediatric haemophilia A patients in Singapore, including its use in the periprocedural setting., Method: This was an observational study conducted at the 2 main haemophilia treatment centres in Singapore. All haemophilia A patients who commenced treatment with emicizumab before 1 July 2022 were recruited., Results: A total of 18 patients with haemophilia A were included in this study. Ten (55.6%) patients had active inhibitors. The median annual bleeding rate for all patients before emicizumab use was 4.5 events (interquartile range [IQR] 2.8-8.3) compared with 0 events (IQR 0-0) after emicizumab was commenced (P=0). There were no adverse events of venous or arterial thrombosis, thrombotic microangiopathy, or death. A total of 6 procedures in 5 patients were performed during the study period with no major bleeding complications., Conclusion: Emicizumab effectively protects against bleeding in haemophilia A patients with and without inhibitors, including in children less than 12 years old. More studies are required to address clinical nuances, such as periprocedural management and the role of immune tolerance in patients with inhibitors on emicizumab.

Objective: Bleeding control measures performed by members of the public can prevent trauma deaths. Equipping public spaces with bleeding control kits facilitates these actions. We modeled a mass casualty incident to investigate the effects of public bleeding control kit location strategies., Methods: We developed a computer simulation of a bomb exploding in a shopping mall. We used evidence and expert opinion to populate the model with parameters such as the number of casualties, the public's willingness to aid, and injury characteristics. Four alternative placement strategies of public bleeding control kits in the shopping mall were tested: co-located with automated external defibrillators (AEDs) separated by 90-second walking intervals, dispersed throughout the mall at 10 locations, located adjacent to 1 exit, located adjacent to 2 exits., Results: Placing bleeding control kits at 2 locations co-located with AEDs resulted in the most victims surviving (18.2), followed by 10 kits dispersed evenly throughout the mall (18.0). One or 2 kit locations placed at the mall's main exits resulted in the fewest surviving victims (15.9 and 16.1, respectively)., Conclusions: Co-locating bleeding control kits with AEDs at 90-second walking intervals results in the best casualty outcomes in a modeled mass casualty incident in a shopping mall.

Competing Interests: Conflicts of interest None disclosed.

Background: There is little evidence to guide the perioperative management of patients on a direct oral anticoagulant (DOAC) in the absence of a last known dose. Quantitative serum titers may be ordered, but there is little evidence supporting this., Aims: This multi-center retrospective cohort study of consecutive surgical in-patients with a DOAC assay, performed over a five-year period, aimed to characterize preoperative DOAC assay orders and their impact on perioperative outcomes., Materials and Methods: Patients prescribed regular DOAC (both prophylactic and therapeutic dosing) with a preoperative DOAC assay were included. The DOAC assay titer was evaluated against endpoints. Further, patients with an assay were compared against anticoagulated patients who did not receive a preoperative DOAC assay. The primary endpoint was major bleeding. Secondary endpoints included perioperative hemoglobin change, blood transfusions, idarucizumab or prothrombin complex concentrate administration, postoperative thrombosis, in-hospital mortality and reoperation. Adjusted and unadjusted linear regression models were used for continuous data. Binary logistic models were performed for dichotomous outcomes., Results: 1065 patients were included, 232 had preoperative assays. Assays were ordered most commonly by Spinal (11.9%), Orthopedics (15.4%), and Neurosurgery (19.4%). For every 10 ng/ml increase in titer, the hemoglobin decreases by 0.5066 g/L and the odds of a preoperative reversal increases by 13%. Compared to those without an assay, patients with preoperative DOAC assays had odds 1.44× higher for major bleeding, 2.98× higher for in-hospital mortality and 16.3× higher for receiving anticoagulant reversal., Conclusion: A preoperative DOAC assay order was associated with worse outcomes despite increased reversal administration. However, the DOAC assay titer can reflect the patient's likelihood of bleeding.