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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).)

The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6 th edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients' population. A panel of experts belonging to the Hematopoietic Cell Transplant and Infectious Disease Working Group (WG) of Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) developed a consensus to define the best practices in prevention, diagnosis, and management of HC in pediatric HCT setting., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

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.)

Competing Interests: Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none.

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.

Introduction: Retrograde Endovascular Balloon Occlusion of the Aorta (REBOA) is an effective management for the transient responder, but the ischemic consequences of complete aortic occlusion currently limit its use. Multiple DoD-funded preclinical studies have clearly demonstrated that partial REBOA reduces distal ischemia to potentially extend safe occlusion times, while still providing effective temporization of noncompressible torso hemorrhage. Early versions of REBOA devices were designed to completely occlude the aorta and had little ability to provide partial occlusion. Recently, a new REBOA device (pREBOA-PRO) was designed specifically to allow for partial occlusion, with the hypothesis that this may reduce the complications of aortic occlusion and extend safe occlusion times while maintaining the benefits on cardiac and cerebrovascular circulation as well as reductions in resuscitation requirements., Materials and Methods: To ascertain the impact of a new purpose-built partial REBOA device on the extension of safe occlusion time, the Partial REBOA Outcomes Multicenter ProspecTive (PROMPT) trial compared available data from the pREBOA-PRO with existing data from 200 clinical uses of pREBOA-PRO and available data in the AAST AORTA Registry were reviewed to design primary endpoints and clinical evidence for a prospective multi-center trial, the PROMPT Study. Together with the endpoints identified in preclinical studies of partial REBOA, primary endpoints for the PROMPT study were identified and power analyses were conducted to determine the target patient enrollment goals., Results: Results from the clinical implementation of partial REBOA at a single trauma center were used to conduct the initial power analysis for the primary endpoint of Acute Kidney Injury (AKI) after prolonged occlusion. The rate of AKI after complete REBOA was 55% (12/20) compared to 33% (4/12) after partial REBOA (Madurska et al., 2021). With an alpha of 0.05 and power (β) of 0.8, the projected sample size for comparison on a dichotomous outcome is 85 patients for the assessment of AKI. Initial power and endpoint analyses have been confirmed and extended with the ongoing analysis of partial and complete REBOA reported in the AORTA database. These analyses confirm preclinical findings which show that compared to complete REBOA, partial REBOA is associated with extended occlusion time in zone 1 (complete: 31 min vs. partial: 45 min, P = 0.003), lower rates of AKI after zone 1 occlusion (complete: 33% vs. partial: 19%, P = 0.05) and reduced resuscitation requirements (e.g., 25% reduction in pRBC administration: complete: 18 units vs. partial: 13 units, P = 0.02)., Conclusions: The DoD-funded PROMPT study of partial REBOA will provide prospective observational clinical data on patients being treated with pREBOA-PRO. Outcomes will be stratified based on partial or complete occlusion to address whether partial REBOA has additional clinical benefits over complete REBOA, such as decreased distal ischemia, extension of safe occlusion time, improved hemodynamics during transition to and from occlusion, and reduced interoperative bleeding and blood product use. The results from this study are expected to confirm previous data demonstrating reduction of ischemic sequalae, improved transition to reperfusion, and reduced resuscitative requirements compared to complete REBOA., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (2 3 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases., (© 2024. The Author(s).)

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.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers. However, the influence of patient-specific demographic, clinical, and other genetic factors on outcomes with genotype-guided DAPT has not been defined. In addition, the impact of genotype-guided de-escalation from prasugrel or ticagrelor to clopidogrel in patients without a CYP2C19 no-function allele has not been investigated in a diverse, real-world clinical setting. The Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry is a multicenter US registry of patients who underwent PCI and clinical CYP2C19 testing. The registry is enrolling a diverse population, assessing atherothrombotic and bleeding events over 12 months, collecting DNA samples, and conducting platelet function testing in a subset of patients. The registry aims to define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19-guided DAPT, evaluate the safety and effectiveness of CYP2C19-guided DAPT de-escalation following PCI in a real-world setting, and identify additional genetic influences of clopidogrel response after PCI, with the ultimate goal of establishing optimal strategies for individualized antiplatelet therapy that improves outcomes in a diverse, real-world population., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Blood accumulation often occurs during bleeding in surgery. Simulating the blood accumulation in surgical simulation system not only enhances the realism and immersion of surgical training, but also helps researchers better understand the physical properties of blood flow., Methods: To realistically simulate the blood accumulation during the bleeding, this paper proposes a novel kernel function with non-negative second derivatives to improve the SPH method. Meanwhile, a simple form of boundary force equation is constructed to impose the solid boundary condition., Results: We simulate the blood accumulation during liver bleeding and vessel bleeding respectively in the surgical simulation system. The simulation results show that there is no occurrence of blood physically penetrating the boundary., Conclusions: Applying the solid boundary condition to the blood by using the method proposed in this paper is not only convenient but can also eliminate compression instability in the blood accumulation simulation., (© 2024 John Wiley & Sons Ltd.)

Objectives: To determine the effectiveness of an updated protocol that increased the transfusion threshold to perform preperitoneal pelvic packing in patients with pelvic ring injuries and hemodynamic instability (HDI)., Design: Retrospective review., Setting: Urban level 1 trauma center., Patients Selection Criteria: Severely injured (injury severity score > 15) patients with pelvic ring injuries treated before and after increasing the threshold to perform preperitoneal pelvic packing from 2 to 4 units of red blood cells (RBCs). HDI was defined as a systolic blood pressure <90 mm Hg., Outcome Measures and Comparisons: Mortality from hemorrhage, anterior pelvic space infections, and venous thromboembolisms before and after increasing preperitoneal pelvic packing threshold., Results: One hundred sixty-six patients were included: 93 treated under the historical protocol and 73 treated under the updated protocol. HDI was present in 46.2% (n = 43) of the historical protocol group and 49.3% (n = 36) of the updated protocol group (P = 0.69). The median age of patients with HDI was 35.0 years (interquartile range 26.0-52.0), 74.7% (n = 59) were men, and the median injury severity score was 41.0 (interquartile range 29.0-50.0). Patients with HDI in the updated protocol group had a lower heart rate on presentation (105.0 vs. 120.0; P = 0.004), required less units of RBCs over the first 24 hours (6.0 vs. 8.0, P = 0.03), and did not differ in age, injury severity score, systolic blood pressure on arrival, base deficit or lactate on arrival, resuscitative endovascular balloon occlusion of the aorta, resuscitative thoracotomy, angioembolization, or anterior pelvis open reduction internal fixation (P > 0.05). The number of PPPs performed decreased under the new protocol (8.3% vs. 65.1%, P < 0.0001), and there were fewer anterior pelvic infections (0.0% vs. 13.9%, P = 0.02), fewer VTEs (8.3% vs. 30.2%; P = 0.02), and no difference in deaths from acute hemorrhagic shock (5.6% vs. 7.0%, P = 1.00)., Conclusions: Increasing the transfusion threshold from 2 to 4 units of red blood cells to perform pelvic packing in severely injured patients with pelvic ring injuries decreased anterior pelvic space infections and venous thromboembolisms without affecting deaths from acute hemorrhage., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: None of the authors have financial conflicts of interest relevant to the content of this study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Access site complications remain common following atrial fibrillation (AF) catheter ablation. Femoral vascular closure devices (VCDs) reduce time to hemostasis compared with manual compression, although large-scale data comparing clinical outcomes between the two approaches are lacking., Methods: Two cohorts of patients undergoing AF ablation were identified from 36 healthcare organizations using a global federated research network (TriNetX): those receiving a VCD for femoral hemostasis, and those not receiving a VCD. A 1:1 propensity score matching (PSM) model based on baseline characteristics was used to create two comparable cohorts. The primary outcome was a composite of all-cause mortality, vascular complications, bleeding events, and need for blood transfusion. Outcomes were assessed during early (within 7 days of ablation) and extended follow-up (within 8-30 days of ablation)., Results: After PSM, 28 872 patients were included (14 436 in each cohort). The primary composite outcome occurred less frequently in the VCD cohort during early (1.97% vs. 2.60%, odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65-0.88; p < .001) and extended follow-up (1.15% vs. 1.43%, OR 0.80, 95% CI 0.65-0.98; p = .032). This was driven by a lower rate of vascular complications during early follow-up in the VCD cohort (0.83% vs. 1.26%, OR 0.66, 95% CI 0.52-0.83; p < .001), and fewer bleeding events during early (0.90% vs. 1.23%, OR 0.73, 95% CI 0.58-0.92; p = .007) and extended follow-up (0.36% vs. 0.59%, OR 0.61, 95% CI 0.43-0.86; p = .005)., Conclusion: Following AF ablation, femoral venous hemostasis with a VCD was associated with reduced complications compared with hemostasis without a VCD., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: The learning curve for new operators performing ultrasound-guided transfemoral access (TFA) remains uncertain., Methods: We performed a pooled analysis of the FAUST (Femoral Arterial Access With Ultrasound Trial) and UNIVERSAL (Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures) trials, both multicenter randomized controlled trials of 1:1 ultrasound-guided versus non-ultrasound-guided TFA for coronary procedures. Outcomes included the composite of major bleeding or vascular complications and successful common femoral artery cannulation. Participants were stratified by the operators' accrued case volume. We used adjusted repeated-measurement logistic regression, with random intercepts for operator clustering, for comparison against the non-ultrasound-guided TFA group and to model the learning curve., Results: The FAUST and UNIVERSAL trials randomized a total of 1624 patients, of which 810 were randomized to non-ultrasound-guided TFA and 814 to ultrasound-guided TFA (cases 1-10, 391; 11-20, 183; and >20, 240). Participants who had operators who performed >20 ultrasound-guided TFAs had a decreased risk for the primary end point (5/240 [2.1%] versus 64/810 [7.9%]; adjusted odds ratio, 0.26 [95% CI, 0.09-0.61]) compared with non-ultrasound-guided TFA. Operators who performed >20 ultrasound-guided procedures had increased odds of successfully cannulating the common femoral artery (224/246 [91.1%] versus 327/382 [85.6%]; adjusted odds ratio, 1.76 [95% CI, 1.08-2.89]) compared with non-ultrasound-guided TFA. The learning curve plots demonstrated growing competence with increasing accrued cases., Conclusions: New operators should perform at least 20 ultrasound-guided TFA to decrease access site complications and increase proper cannulation compared with non-ultrasound-guided TFA. Additional accrued cases may lead to increased proficiency. Training programs should consider these findings in the transradial era., Competing Interests: Dr d’Entremont is a Canadian Institutes of Health Research Canada Graduate Scholarship awardee. Dr Jolly reports receiving grants or contracts from Boston Scientific and payment or honoraria for lectures, presentations, speaker’s bureaus, article writing, or educational events from Penumbra, Teleflex, and Abiomed. Dr Seto reports receiving grants or contracts from Arena Medical, Philips, and ACIST; payment or honoraria for speaker’s bureaus from Janssen, Terumo, Gettinge, and GE Healthcare; consulting fees from Medtronic and Medicure; and reports having equity in Frond Medical. The other authors report no conflicts.

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: 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.)

Background: Patients with cardiogenic shock or end-stage heart failure can be maintained on mechanical circulatory support (MCS) devices. Once a patient undergoes placement of a device, obtaining and maintaining therapeutic anticoagulation is vital. Guidelines recommend the use of institutional protocols to assist in dosing and titration of anticoagulants., Objective: The purpose of this study was to characterize the use of bivalirudin before and after the implementation of a standardized titration protocol in patients with MCS., Methods: A retrospective review of patients who received bivalirudin for MCS (VA ECMO [veno-arterial extracorporeal membrane oxygenation], Impella, or LVAD [left ventricular assist device]) before and after the implementation of the titration protocol into the electronic health record (EHR) was conducted. The primary outcome was to compare the proportion of therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included number of subtherapeutic and supratherapeutic aPTTs, incidence of bleeding and clotting events, bivalirudin titrations per day, and percentage of patients with therapeutic aPTT level., Results: A total of 100 patients were included (precohort = 67; postcohort = 33). The proportion of therapeutic aPTTs was significantly higher in the postcohort than that in the precohort (62% vs 48%; P < 0.001). The postcohort had 0% of patients failing to achieve therapeutic aPTT levels. The number of titrations per day was significantly lower in the postcohort, with 1.20 titrations per day versus 1.93 in the precohort ( P < 0.001)., Conclusions: Implementation of the bivalirudin titration nomograms within the EHR significantly increased the number of therapeutic aPTTs, reduced the number of patients who never achieved a therapeutic aPTT, and reduced the required number of titrations per day., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

The history of anticoagulation has evolved considerably, from non-specific drugs to molecules that directly target specific coagulation factors, such as direct oral anticoagulants (DOACs). Since last decade, DOACs are widely used in clinical practice because of their ease to use with favorable pharmacological profile and not requiring monitoring. New therapeutics targeting the contact phase of coagulation are currently under development, and could make it possible to prevent thrombotic risk without altering hemostasis, thereby reducing the risk of bleeding. Factor XII, being at the crossroads between hemostasis and inflammation, appears to be an interesting target that could limit thrombo-inflammation without increasing bleeding risk. The aim of this article is to summarize the main information concerning FXII inhibitors and to review the results of various clinical trials available to date, focusing on applications beyond hemostasis, such as in the management of hereditary angioedema., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Differences in the efficacy and safety between the preclose and postclose suture-mediated vascular closure systems for femoral vein access have not been adequately studied., Objectives: This study aimed to evaluate the efficacy and safety of these 2 suturing techniques in femoral vein access., Methods: Patients subjected to elective catheter ablation via the femoral vein using a sheath of 8- to 13-F inner diameter (n = 282) were randomized to the preclose or postclose groups for the single-suture technique using ProGlide/ProStyle (Abbott Vascular). Duplex ultrasound was performed on days 1 and 90 after the procedure to evaluate vascular complications. The primary efficacy endpoint was rebleeding requiring recompression, and the primary safety endpoint was any major complication occurring within 90 days. The secondary efficacy endpoints included time to hemostasis and time to ambulation, and the secondary safety endpoint was any minor complication occurring within 90 days., Results: The preclose group demonstrated a significantly lower rebleeding rate (5 of 141 [3.5%] vs 15 of 141 [10.6%]; P = 0.03) and shorter time to hemostasis (254.0 ± 120.4 seconds vs 299.8 ± 208.2 seconds; P = 0.02) compared with the postclose group. Five patients in each group were lost to follow-up at 90 days. Incidence of major complications were similar in both groups (1 of 136 [0.7%]; P = 1.00), whereas minor complications were observed in 18 of 136 (13.2%) and 21 of 136 (15.4%) patients in the preclose and postclose groups, respectively, without a significant difference (P = 0.73)., Conclusions: In femoral vein access using the single-suture technique with ProGlide/ProStyle, the preclose technique presented a higher hemostasis rate than the postclose technique, without compromising safety., Competing Interests: Funding Support and Author Disclosures The 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: 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.)

Background: Transfemoral access is often used when large-bore guide catheters are required for percutaneous coronary intervention (PCI) of complex coronary lesions, especially when large-bore transradial access is contraindicated. Whether the risk of access site complications for these procedures may be reduced by ultrasound-guided puncture is unclear., Aims: We aimed to show the superiority of ultrasound-guided femoral puncture compared to fluoroscopy-guided access in large-bore complex PCI with regard to access site-related Bleeding Academic Research Consortium 2, 3 or 5 bleeding and/or vascular complications requiring intervention during hospitalisation., Methods: The ULTRACOLOR Trial is an international, multicentre, randomised controlled trial investigating whether ultrasound-guided large-bore femoral access reduces clinically relevant access site complications compared to fluoroscopy-guided large-bore femoral access in PCI of complex coronary lesions., Results: A total of 544 patients undergoing complex PCI mandating large-bore (≥7 Fr) transfemoral access were randomised at 10 European centres (median age 71; 76% male). Of these patients, 68% required PCI of a chronic total occlusion. The primary endpoint was met in 18.9% of PCI with fluoroscopy-guided access and 15.7% of PCI with ultrasound-guided access (p=0.32). First-pass puncture success was 92% for ultrasound-guided access versus 85% for fluoroscopy-guided access (p=0.02). The median time in the catheterisation laboratory was 102 minutes versus 105 minutes (p=0.43), and the major adverse cardiovascular event rate at 1 month was 4.1% for fluoroscopy-guided access and 2.6% for ultrasound-guided access (p=0.32)., Conclusions: As compared to fluoroscopy-guided access, the routine use of ultrasound-guided access for large-bore transfemoral complex PCI did not significantly reduce clinically relevant bleeding or vascular access site complications. A significantly higher first-pass puncture success rate was demonstrated for ultrasound-guided access., Clinicaltrials: gov identifier: NCT04837404.

Objective: Coronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery., Methods: This was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias., Results: A total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events., Conclusions: Postoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice., (© 2024. The Author(s).)

Abstract: Neuraxial blockade procedures are essential for anesthesia and pain management but pose risks in patients with uncertain coagulation profiles. Traditional coagulation tests often fail to predict bleeding risks associated with neuraxial blockade. Thromboelastography (TEG) offers real-time insights into coagulation status, potentially improving safety outcomes. In this case series, six patients underwent neuraxial blockade guided by TEG analysis. An individualized anesthetic plan was formulated based on TEG findings to mitigate bleeding risks while ensuring pain management. Tailoring anesthetic techniques to real-time TEG data improved safety outcomes with minimized bleeding complications and satisfactory pain control. In conclusion, neuraxial blockade guided by TEG enhances safety in patients with uncertain coagulation profiles. Further studies are needed to validate benefits in broader clinical settings., (Copyright © 2024 Copyright: © 2024 Journal of Postgraduate Medicine.)

Objectives: To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference., Data Sources: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021., Study Selection: Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs)., Data Extraction: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form., Measurements and Main Results: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented., Conclusions: Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies., Competing Interests: The Executive Committee (Drs. Alexander, Muszynski, Bembea, Cheifetz, Steiner, and Barbaro) served as arbitrators for conflict of interest management. Dr. Alexander’s institution received funding from Novartis (Prospective Trial to Assess the Angiotensin Receptor Blocker NeprilysinInhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatmentof Pediatric HF [PANORAMA-HF]). Dr. Ryerson received an honorarium from the Instrumentation Laboratory for consultation work. Dr. Ryerson disclosed the off-label product use of antifibrinolytic agents (epsilon-aminocaproic acid and tranexamic acid) and topical hemostatic agents. Drs. Alexander and Muszynski’s institutions received funding from the National Institutes of Health (NIH) and received support for article research from the NIH. Dr. Alexander’s institution received funding from the Extracorporeal Life Support Organization and Novartis. Dr. Steiner’s institution received funding from the Department of Defense; she received funding from Octapharma and Medtronic; she disclosed she was on the Data Safety and Monitoring Board for the Pumps for Kids, Infants and Neonates (PumpKIN) Trial; she disclosed the off-label product use of rFVIIa, Kcentra, antithrombin, tranexamic acid, and Amicar. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

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.)

Background: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a potentially life-saving intervention to treat noncompressible torso hemorrhage. Traditionally, REBOA use has been limited to surgeons. However, emergency physicians are often the first point-of-contact and are well-versed in obtaining rapid vascular access and damage control resuscitation, making them ideal candidates for REBOA training., Study Objectives: To fill this gap, we designed and evaluated a REBOA training curriculum for emergency medicine (EM) residents., Methods: Participants enrolled in an accredited 4-year EM residency program (N = 11) completed a 12-hour REBOA training course. Day 1 included lectures, case studies, and hands-on training using REBOA task trainers and perfused cadavers. Day 2 included additional practice and competency evaluations. Assessments included a 25-item written knowledge exam, decision-making on case studies, REBOA placement success, and time-to-placement. Participants returned at 4 months to assess long-term retention. Data were analyzed using t-tests and nonparametric statistics at p < 0.05., Results: Scores on a 25-item multiple choice test significantly increased from pre-training (65% ± 5%) to post-training (92% ± 1%), p < 0.001. On Day 2, participants scored 100% on correct recognition of REBOA indications and scored 100% on correct physical placement of REBOA. Exit surveys indicated increased preparedness, confidence, and support for incorporating this course into EM training. Most importantly, REBOA knowledge, correct recognition of REBOA indications, and correct REBOA placement skills were retained by the majority of participants at 4 months., Conclusion: This course effectively teaches EM residents the requisite skills for REBOA competence and proper placement. This study could be replicated at other facilities with larger, more diverse samples, aiming to expand the use of REBOA in emergency physicians and reducing preventable deaths in trauma., 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., (Published by Elsevier Inc.)

Introduction: Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8-1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8-1 enrolment since emicizumab was an investigational therapy at the time of trial initiation., Aim: Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec., Methods: To estimate bleeding risk at weekly intervals following valoctocogene roxaparvovec infusion, a published emicizumab pharmacokinetic model was used to simulate emicizumab concentrations and merged with FVIII activity time-course data for participants in GENEr8-1. The analysis investigated three approved emicizumab dosing regimens for two transition scenarios that varied whether the last dose of emicizumab was administered on the same day or 4 weeks after valoctocogene roxaparvovec infusion., Results: Simulations demonstrated administering the last emicizumab dose the day of valoctocogene roxaparvovec infusion and 4 weeks after offered similar levels of haemostatic control, and bleeding risk was similar for all emicizumab dosing regimens. An algorithm was developed to provide guidance for discontinuation of emicizumab. Theoretical cases based on GENEr8-1 participants are presented to illustrate how decisions may vary among individuals., Conclusion: Pharmacokinetic simulations demonstrated no clinically meaningful difference in bleeding risk caused by decaying emicizumab levels and rising gene therapy-derived endogenous FVIII for all examined emicizumab doses and dosing regimens. Therefore, multiple approaches can safely transition individuals from emicizumab prophylaxis to valoctocogene roxaparvovec., (© 2024 BioMarin Pharmaceutical Inc and The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38 kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery., (© 2024 Wiley‐VCH GmbH.)

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a tool for hemorrhage control. We describe a case where the REBOA Catheter needed to be removed prior to hemorrhage control. The patient is a 40-year-old man that presented following motor vehicle collision. A REBOA Catheter was placed via the right common femoral artery (CFA). CT scan demonstrated extravasation from the left inferior epigastric artery. The Interventional Radiology (IR) team would only be able to perform angioembolization via contralateral access where the REBOA Catheter was in place. Prior to removing the REBOA Catheter on the right, left CFA access was obtained in the event a new catheter needed to be deployed. Ultimately, IR performed angioembolization without a second REBOA Catheter. In gaining contralateral access prior to removing the REBOA Catheter, this case provides a strategy for expeditious replacement of REBOA Catheters in situations where the catheter interferes with hemorrhage control procedures., 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.

Hemostatic materials play a crucial role in trauma medicine. However, existing materials have poor hemostatic efficacy and a tendency to adhere to the wound surface, limiting their clinical effectiveness. Herein, a drug-loaded, superhydrophilic/superhydrophobic laminated material (DSLM), consisting of a superhydrophobic inner layer with a micropore array, a superhydrophilic chitosan-based sponge layer loaded with hemostatic/antimicrobial drugs, and a superhydrophobic outer layer, was developed. Furthermore, the DSLM allows unidirectional flow of blood and exudates from the wound bed through the superhydrophobic inner layer while facilitating efficient drug delivery. In addition, it possesses excellent biocompatibility and antiadhesion properties, as confirmed by in vivo and in vitro experiments. Compared with traditional hemostatic materials, the DSLM remarkably increased the survival time by over threefold in the acute femoral transaction wound bleeding model, and simultaneously prevented secondary wound damage by reducing peeling force to one-eighth incomparison to pristine gauze. The DSLM holds promise as a versatile clinical biomaterial for prehospital acute trauma treatment, with its simple structure facilitating manufacturing and expanding applications in biomedicine., 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: Venous thromboembolism (VTE) continues to be a major cause of morbidity in trauma. It is unclear whether the type of hemorrhage control procedure (i.e., splenectomy versus angioembolization) is associated with an increased risk of VTE. We hypothesize that hemodynamically stable patients undergoing angioembolization for blunt high-grade splenic injuries have lower rates of VTE compared to those undergoing splenectomy., Methods: The American College of Surgeons Trauma Quality Program dataset from 2017 to 2019 was queried to identify all patients with American Association for the Surgery of Trauma grade 3-5 blunt splenic injuries. Outcomes including VTE rates were compared between those who were managed with splenectomy versus angioembolization. Propensity score matching (1:1) was performed adjusting for age, sex, initial vital signs, Injury Severity Score, and splenic injury grade., Results: The analysis included 4698 matched patients (splenectomy [n = 2349] and angioembolization [n = 2349]). The median (interquartile range) age was 41 (27-58) years and 69% were male. Patients were well matched between groups. Angioembolization was associated with significantly lower VTE than splenectomy (2.2% versus 3.4%, P = 0.010) despite less use of VTE chemoprophylaxis (70% versus 80%, P < 0.001), as well as a relative delay in initiation of chemoprophylaxis (44 h versus 33 h, P < 0.001). Hospital and intensive care unit length of stay and mortality were also significantly lower in the angioembolization group., Conclusions: Angioembolization is associated with a significantly lower incidence of VTE than splenectomy. Thus, angioembolization should be considered for initial management of hemodynamically stable patients with high-grade blunt splenic injuries in whom laparotomy is not otherwise indicated., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To assess the safety and effectiveness of turoctocog alfa in previously treated patients (PTPs) and previously untreated patients (PUPs) with haemophilia A in a real-world setting in Japan., Methods: This multicentre, non-interventional, post-marketing study recruited patients with haemophilia A who initiated treatment with turoctocog alfa from 18 sites (08/2014-12/2018). The primary endpoint was adverse events (AEs) during the 2-year study period., Results: The safety and effectiveness analysis set included 39 patients. In total, 13 (33.3%) patients reported ≥1 AE; incidence rate was 60.4 events/100 patient-years of exposure (PYE). Treatment was withdrawn in two cases: pruritus in a PTP and factor VIII inhibitor development in a PUP. Inhibitor development occurred in 2.6% of all patients, with an incidence rate of 3.8 events/100 PYE. The rate of inhibitor development was 0%, 25% and 20% in PTPs, PUPs and PUPs with severe type, respectively. The haemostatic success rate was 91.4% for 383 bleeding episodes and 85.7% for 14 surgeries. The negative binomial annualised bleeding rate for the prophylaxis regimen was 6.19 episodes/year (95% CI, 3.69-10.38). The mean (SD) total consumption of turoctocog alfa ( n  = 34; excluding FVIII inhibitors) was 5,382.6 (7,180.1) IU/kg/year/patient; consumption was 4,133.1 (1,452.4) IU/kg/year/patient for prophylaxis., Discussion: The effectiveness and safety profiles were comparable to those observed in other turoctocog alfa trials; effectiveness analysis and consumption were not affected by treatment regimens., Conclusion: Long-term use of turoctocog alfa therapy in clinical practice posed no newly identified safety issues and was effective for prophylaxis and treatment of bleeds in patients with haemophilia A in Japan.

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.)

Acute hemorrhage is a major cause of death in many emergency cases. Although many hemostatic materials have been studied in recent years, it is still necessary to develop new hemostatic materials with remarkable efficiency, biosafety, convenient preparation, low cost, and good biodegradability. In this work, novel chitosan (CS)/β-glycerophosphate (β-GP) composite porous microsphere with a uniform size of 210.00 ± 2.14 μm was fabricated through water-in-water (W/W) emulsion via microencapsulation, which can avoid the use of toxic crosslink chemicals and organic solvents to achieve facile and efficient preparation of microspheres. β-GP could promote the formation of microspheres by enhancing the hydrogen-bonding interaction between CS chains, which contributed to the macro-porous structure. Owing to their large pore size (6.0 μm) and high specific surface area (37.8 m 2 /g), the CS/β-GP microspheres could absorb water quickly and adsorb protein, red blood cells, and platelets through electrostatic forces to promote blood coagulation. Furthermore, the CS/β-GP microspheres achieved a significantly shortened hemostatic time (45 s) and reduced blood loss (0.03 g) in a rat liver injury model. Rat tail amputation test also showed a satisfactory hemostatic effect. Overall, the green and porous CS/β-GP microspheres can be used as a facile and topical rapid hemostatic material., 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.)

Purpose: Prophylactic platelet transfusions (PT) aim to reduce bleeding. We assessed whether restrictive PT compared to prophylactic strategy could apply in ICU., Material and Methods: We conducted a retrospective monocentric study including patients >18 yo with haematological malignancy admitted to the ICU with thrombocytopenia <20 G/L between 2018 and 2021. Patients were classified in 2 groups according transfusion strategy applied during the first 3 days: prophylactic or restrictive transfusion., Results: 180 patients were included, 87 and 93 in the restrictive and prophylactic groups respectively. After propensity-score analysis, 2 groups of 54 matched patients were analyzed. Restrictive strategy led to a significant reduction in PT with incidence rate for 100-ICU-patients-days of 34.9 and 49.9, incidence rate ratio = 0.699 [0.5-0.9], p = 0.006, representing a 31% decrease. Decreased PT persisted until day 28 with platelet concentrates transfusions-free days at day 28 of 21 [13-25] and 16.5 [10.2-21] in the 2 groups (p = 0.04). Restrictive strategy did not result in higher grade ≥ 2 bleeding. Transfusion efficiency was low with similar number of days with platelet <10 or < 20 G/L regardless of strategy. Platelet transfusion strategy was not associated with 28-day mortality. Platelet nadir <5G/L was associated with day-28 mortality with HR = 1.882 [1.011-3.055], p = 0.046., Conclusion: A restrictive PT strategy appears feasible in the ICU., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

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.)

There remains no optimal anticoagulation protocol for continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in pediatric patients with elevated D-dimer levels. We aimed to assess the effects of different anticoagulation strategies on the risk of CRRT filter clotting in these patients. Pediatric patients undergoing CRRT were retrospectively grouped based on pre-CRRT D-dimer levels and anticoagulant: D-RCA group (normal D-dimer, RCA only, n = 22), D+ RCA group (elevated D-dimer, RCA only, n = 50), and D+ RCA+ systemic heparin anticoagulation (SHA) group (elevated D-dimer, RCA combined with SHA, n = 55). The risk of filter clotting and incidence of bleeding were compared among the groups. Among the groups, the D+ RCA+ SHA group had the longest filter lifespan; further, the incidence of bleeding was not increased by concurrent use of low-dose heparin for anticoagulation. Moreover, concurrent heparin anticoagulation was associated with a decreased risk of filter clotting. Contrastingly, high pre-CRRT hemoglobin and D-dimer levels and post-filter ionized calcium level > 0.4 mmol/L were associated with an increased risk of filter clotting. RCA combined with low-dose heparin anticoagulation could reduce the risk of filter clotting and prolong filter lifespan without increasing the risk of bleeding in patients with elevated D-dimer levels undergoing CRRT., (© 2024. The Author(s).)

Regional anesthesia has a strong role in minimizing post-operative pain, decreasing narcotic use and PONV, and, therefore, speeding discharge times. However, as with any procedure, regional anesthesia has both benefits and risks. It is important to identify the complications and contraindications related to regional anesthesia, which patient populations are at highest risk, and how to mitigate those risks to the greatest extent possible. Overall, significant complications secondary to regional anesthesia remain low. While a variety of different regional anesthesia techniques exist, complications tend to fall within 4 broad categories: block failure, bleeding/hematoma, neurological injury, and local anesthetic toxicity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Anticoagulation is the first-line approach in the prevention and treatment of pulmonary embolism. In some instances, however, anticoagulation fails, or cannot be administered due to a high risk of bleeding. Inferior vena cava filters are metal alloy devices that mechanically trap emboli from the deep leg veins halting their transit to the pulmonary circulation, thus providing a mechanical alternative to anticoagulation in such conditions. The Greenfield filter was developed in 1973 and was later perfected to a model that could be inserted percutaneously. Since then, this model has been the reference standard. The current class I indication for this device includes absolute contraindication to anticoagulants in the presence of acute thromboembolism and recurrent thromboembolism despite adequate therapy. Additional indications have been more recently proposed, due to the development of removable filters and of progressively less invasive techniques. Although the use of inferior vena cava filters has solid theoretical advantages, clinical efficacy and adverse event profile are still unclear. This review analyzes the most important studies related to such devices, open issues, and current guideline recommendations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Grant FOR READINGS/SPEECHES AT CONFERENCES: Chiesi, GSK, Firma, Guidotti, Sanofi, Astrazeneca. Project with drug development: Chiesi and Astrazeneca. Project without drug development: GSK., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control. Therefore, the comparative effectiveness of valoctocogene roxaparvovec vs FVIII prophylaxis was evaluated using propensity scoring (PS)., Methods: This post hoc analysis compared 112 participants from GENEr8-1 (treated cohort) to 73 participants in 270-902 who did not enroll in GENEr8-1 (control cohort). The primary analysis used standardized mortality ratio weighting to re-weight baseline characteristics of the control cohort to better match the treated cohort. Mean annualized bleeding rates (ABR) for treated and all bleeds were compared between cohorts along with the proportion of participants with zero bleeds (treated and all bleeds). Sensitivity and scenario analyses were also conducted., Results: PS adjustments reduced differences in baseline characteristics between cohorts. Mean treated (4.40 vs 0.85; P < 0.001) and all (5.01 vs 1.54; P < 0.001) ABR were significantly lower, and the proportions of participants with zero treated bleeds (82.1% vs 32.9%; P < 0.001) and all bleeds (58.0% vs 28.5%; P < 0.001) were significantly higher in GENEr8-1., Conclusions: PS-adjusted analyses were consistent with prior intra-individual comparisons. Compared with participants receiving prophylactic FVIII, the participants receiving valoctocogene roxaparvovec experienced lower ABR, and a higher proportion had zero bleeds., Trail Registration: ClinicalTrials.gov identifier, NCT03370913., (© 2024. The Author(s).)

Study Objective: To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function., Design: Systematic review and meta-analysis of randomized controlled trials., Setting: We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023., Patients: Patients undergoing non-obstetric surgery., Interventions: Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid., Measurement: We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function., Main Results: We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m 2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m 2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min., Conclusions: The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown., Competing Interests: Declaration of competing interest No author reported any competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: An increasing number of interventional procedures require large-sheath technology (>12F) with a favorable outcome with endovascular rather than open surgical access. However, vascular complications are a limitation for the management of these patients. This trial aimed to determine the effectiveness and safety of the Cross-Seal suture-mediated vascular closure device in obtaining hemostasis at the target limb access site following interventional procedures using 8F to 18F procedural sheaths., Methods: The Cross-Seal IDE trial (Investigational Device Exemption) was a prospective, single-arm, multicenter study in subjects undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheaths. The primary efficacy end point was time to hemostasis at the target limb access site. The primary safety end point was freedom from major complications of the target limb access site within 30 days post procedure., Results: A total of 147 subjects were enrolled between August 9, 2019, and March 12, 2020. Transcatheter aortic valve replacement was performed in 53.7% (79/147) and percutaneous endovascular abdominal/thoracic aortic aneurysm repair in 46.3% (68/147) of subjects. The mean sheath ID was 15.5±1.8 mm. The primary effectiveness end point of time to hemostasis was 0.4±1.4 minutes. An adjunctive intervention was required in 9.2% (13/142) of subjects, of which 2.1% (3/142) were surgical and 5.6% (8/142) endovascular. Technical success was achieved in 92.3% (131/142) of subjects. Freedom from major complications of the target limb access site was 94.3% (83/88)., Conclusions: In selected patients undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheath, Cross-Seal suture-mediated vascular closure device achieved favorable effectiveness and safety in the closure of the large-bore arteriotomy., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03756558., Competing Interests: Disclosures Dr Krishnan has served as a consultant to Abbott and Medtronic. Dr Nazif reports consulting fees or honoraria from Terumo Medical, Boston Scientific, Medtronic, Edwards Lifesciences, Teleflex, Opsens Medical, Encompass Technologies, and Columbia University Irving Medical Center. The other authors report no conflicts.