Search

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro‐oncology experts convened to provide practical clinical guidance for the off‐label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low‐molecular‐weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT. There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants, specifically in brain tumor patients, but they are widely used for venous thromboembolism in this population. A group of neuro‐oncology experts convened to provide practical clinical guidance for the off‐label use of direct oral anticoagulants in treating venous thromboembolism in patients with brain tumors. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), poses a significant risk of morbidity and mortality in surgical patients, especially those undergoing head and neck cancer surgery with microvascular free flap reconstruction. These patients are at a heightened risk of VTE due to numerous patient and surgical risk factors. VTE chemoprophylaxis guidelines in these patients are limited due to a distinct paucity of research. This study aims to contribute to this scarcity of information, providing guidance for surgeons., Methods: This retrospective cohort study evaluated the efficacy and safety of subcutaneous unfractionated heparin administered every 8 h versus every 12 h for postoperative VTE prophylaxis in patients undergoing head and neck resections with immediate free flap reconstruction. Data was collected from hospital medical records between January 2010 to December 2021. Patient demographics, operative details, and outcomes, including incidence of VTE and bleeding complications, were analyzed., Results: Among 622 patients, those receiving heparin every 8 h (n = 393) demonstrated a significantly lower rate of VTE (0.8%) compared to 12-hourly group (n = 229; 3.9%) (p = 0.006). Additionally, there were no significant differences in the rates of postoperative hematoma between the two groups (9.4% versus 7.9% respectively, p = 0.510)., Conclusion: Our study suggests that an increased daily dose of unfractionated heparin every 8 h for VTE chemoprophylaxis is superior to a 12-hourly regimen with comparable bleeding profiles. Further multicentre, prospective studies are needed to validate these results and compare the efficacy and safety of unfractionated heparin with other agents such as low-molecular-weight heparin in this patient group., (© 2024 Wiley Periodicals LLC.)

Anticoagulation management in the surgical patient requires clinical expertise and careful attention. For patients already receiving anticoagulation for a defined indication (ie, stroke prevention for atrial fibrillation, treatment of venous thromboembolism (VTE), or presence of a mechanical heart valve), understanding how to manage these agents by weighing the risks of thromboembolic events and bleeding is paramount. Additionally, prevention of VTE in the surgical patient involves the identification of patient-specific and procedure-specific risk factors for both VTE and bleeding. With this information, as well as familiarity with the several antithrombotic options available, an appropriate prophylaxis strategy can be employed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hyponatraemia is a prevalent electrolyte disturbance observed in critically ill patients. The rapid correction of low plasma sodium levels by continuous renal replacement therapy (CRRT) carries the risk of developing osmotic demyelination syndrome (ODS), which can be prevented by implementing an individualized CRRT method., Aim: This study aims to introduce a CRRT protocol for the safe and gradual correction of severe hyponatraemia., Study Design: This retrospective case series study was conducted in an intensive care unit (ICU). All four patients with severe hyponatraemia (<125 mmol/L) and renal failure between October 1, 2022, and September 30, 2023, were treated by CRRT with sterile water and regional citrate anticoagulation (RCA). Data on patient demographics, laboratory biochemical parameters, urine outputs and CRRT-related adverse events were collected. Laboratory parameters and urine outputs were compared by paired t-tests before and after CRRT., Results: After CRRT, sodium levels were significantly increased (112.7 ± 6.7 vs. 141.9 ± 2.8 mmol/L, p = .005). Abnormal urine outputs, potassium, creatinine and bicarbonate were corrected (p for all <.05). Safe and gradual correction of hyponatraemia and internal environmental dysregulation was achieved in all patients without any complications related to CRRT, particularly ODS., Conclusion: It is a novel and simple strategy to correct severe hyponatraemia effectively while ensuring the safety of patients that can be easily implemented by experienced nurse staff., Relevance to Clinical Practice: The sterile water-based protocol for postfilter dilution is safe to correct severe hyponatraemia with RCA and can be easily performed by experienced critical care nurses according to the precalculated formula. CRRT-trained, experienced ICU nurses are competent to initiate and adjust sterile water infusion discretely to prevent overcorrection of hyponatraemia., (© 2024 The Author(s). Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Introduction: Vitamin-K antagonists (VKA) are considered the first-line anticoagulants for thrombotic antiphospholipid syndrome (TAPS), particularly with triple positivity or arterial events. However, thrombotic recurrence remains high despite anticoagulation and other clinical issues may arise. Long-term parenteral anticoagulants may therefore be considered, however little is known about the viability of fondaparinux in this setting., Materials and Methods: We describe the efficacy and safety of long-term fondaparinux for TAPS (>3-months duration) treated at a single centre in the UK. Clinical features and the outcomes of recurrence and bleeding were reviewed using electronic patient records., Results: 46 patients were identified with history of either venous or arterial TAPS and a total 175 patient-years using fondaparinux (median duration 2.7 years/patient (IQR 1.4-4.8)). 43 (93%) had VKA as first-line anticoagulation with a median duration of 6.5 years (IQR 4.0 - 9.8). All patients received fondaparinux as second-to fourth-line anticoagulation.Thrombosis recurrence occurred in 1 (1%) patient (0.6 events/100-patient years). Major, clinically relevant non-major (CRNM) or minor bleeding occurred in 2 (7%), 5 (10.9%) and 8 (17.4%) patients respectively. Major/CRNM bleeding rates were 1.1 and 2.9 events/100-patient-years. Age >65years was associated with bleeding ( p = .047) and concurrent antiplatelets were associated with major/CRNM bleeding ( p = .011). Logistic regression showed increasing age was associated with bleeding (OR = 1.097, p = .009)., Conclusions: We suggest that fondaparinux may be used for TAPS when VKA is not appropriate. Thrombotic recurrence was infrequent, and the number of major bleeding events appeared comparable to conventional therapies., 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.

Introduction: Surgery is often delayed in patients with proximal femoral fractures who receive oral anticoagulants, to avoid complications related to perioperative bleeding. However, surgery delay may increase the risk of postoperative mortality. Our primary goal was to understand whether anticoagulated patients benefit from early surgery in terms of survival and perioperative complications., Methods: This is a multicenter retrospective cohort study of 581,189 patients with proximal femoral fractures. About 2.0 % (n = 11,385) received direct oral anticoagulants (DOAC) and 1.5 % (n = 8,726) received warfarin. Surgery was performed within 48 h in 37.6 % of DOAC patients, 27.6 % of warfarin patients and in 41.9 % of nonanticoagulated patients. Survival analysis was applied to compare mortality rate, blood transfusions, systemic complications and surgical complications during hospitalization between the study groups., Results: Patients receiving anticoagulation were older and had more comorbidities than patients without anticoagulation. There were overall similar rates of mortality (0.8 %, 1.1 % and 1.2 %) and surgical complications (2.1 %, 2.1 % and 2.2 %) in non-anticoagulated, DOAC and warfarin patients. Blood transfusions and systemic complications were higher in all anticoagulated patients regardless of surgery timing. There were comparable rates of early surgery (41.9 %, 37.6 % and 27.6 %, respectively). When operated early, DOAC patients had more surgical complications (OR=1.24, p = 0.04). Warfarin patients operated early had higher mortality (OR=1.48, p = 0.08) and higher risk of blood transfusions (OR=1.24, p < 0.001)., Discussion: Age and comorbidities could explain higher rates of postoperative systemic complications in anticoagulated patients. Nevertheless, overall short-term mortality was similar between the groups. Early surgery was associated with higher rates of surgical complications in DOAC patients. When operated early, patients receiving warfarin were at an increased risk of mortality (p = 0.08) and perioperative blood transfusions., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Direct oral anticoagulants are the primary stroke prevention option in patients with atrial fibrillation. Anticoagulant use before stroke, however, might inhibit clinician comfort with thrombolysis if a stroke does occur. Resuming anticoagulants after ischemic stroke is also problematic for fear of hemorrhage. We describe extensive literature showing that thrombolysis is safe after stroke with direct anticoagulant use. Early reinstitution of direct anticoagulant treatment is associated with lower risk of embolic recurrence and lower hemorrhage risk. The use of direct anticoagulants before, during, and after thrombolysis appears to be safe and is likely to promote improved outcomes after ischemic stroke. ANN NEUROL 2024;96:871-886., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Direct oral anticoagulants (DOACs) have shown comparable efficacy and a superior safety profile in clinical trials for patients with venous thromboembolism (VTE). However, further study is needed to assess DOACs' effectiveness and safety compared to warfarin in a real-world context. Thus, this meta-analysis compares the effectiveness and safety of warfarin and DOACs in patients with VTE., Method: A systematic review of the literature using PubMed and EMBASE was conducted from inception until June 2024. We examined observational studies that compared safety and effectiveness between DOACs and warfarin when used in treating VTE and reported adjusted hazard ratios (HRs) and/or odds ratios (ORs) for recurrent VTE, major bleeding, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and death from any cause. We then estimated the pooled effect using the random-effects model for meta-analysis., Results: A total of 25 studies were included in the current meta-analysis. DOAC therapy was associated with significantly lower risks of recurrent VTE (HR 0.76, 95% confidence interval [CI] 0.69-0.85), major bleeding (HR 0.77, 95% CI 0.72-0.83), clinically relevant non-major bleeding (HR 0.82, 95% CI 0.77-0.88), and gastrointestinal bleeding (HR 0.75, 95% CI 0.68-0.83) compared to warfarin. However, no statistically significant difference was observed in all-cause mortality between the two groups (HR 0.96, 95% CI 0.83-1.10)., Conclusion: This meta-analysis found that DOACs are associated with a significant reduction in VTE recurrence in addition to the known favorable safety profile when compared to warfarin., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: In patients with atrial fibrillation (AF), the association between cancer and cardioembolic or bleeding risk during oral anticoagulant therapy still remains unclear., Purpose: We aimed to assess the impact of cancer present at baseline (CB) or diagnosed during follow-up (CFU) on bleeding events in patients treated with direct oral anticoagulants (DOACs) for non-valvular AF (NVAF) compared with patients without CB or CFU, respectively., Methods: All consecutive patients with NVAF treated with DOACs for stroke prevention were enrolled between January 2017 and March 2019. Primary outcomes were bleeding events or cardiovascular death, non-fatal stroke and non-fatal myocardial infarction, and the composite endpoint between patients with and without CB and between patients with and without CB., Results: The study population comprised 1170 patients who were followed for a mean time of 21.6 ± 9.5 months. Overall, 81 patients (6.9%) were affected by CB, while 81 (6.9%) were diagnosed with CFU. Patients with CFU were associated with a higher risk of bleeding events and major bleeding compared with patients without CFU. Such an association was not observed between the CB and no CB populations. In multivariate analysis adjusted for anemia, age, creatinine, CB and CFU, CFU but not CB remained an independent predictor of overall and major bleeding (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.8-3.89, p < 0.001; HR 3.02, 95% CI 1.6-3.81, p = 0.001, respectively)., Conclusion: During follow-up, newly diagnosed primitive or metastatic cancer in patients with NVAF taking DOACs is a strong predictor of major bleeding regardless of baseline hemorrhagic risk assessment. In contrast, such an association is not observed with malignancy at baseline. Appropriate diagnosis and treatment could therefore reduce the risk of cancer-related bleeding., (© 2024. The Author(s).)

Direct oral anticoagulants (DOACs) are the first-line anticoagulants for the secondary prevention of venous thromboembolism (VTE). However, patients with severe inherited thrombophilias represent a group in whom the efficiency and safety of DOACs is poorly studied. In this communication, we focus on the utility of DOACs in the secondary prevention of VTE in patients with severe thrombophilia. Current evidence is based only on cohort or single-center studies, and poor data are available on compliance of the patients in the studies. Analysis of the studies suggested that full-dose DOACs and vitamin K antagonists have a similar efficacy and bleeding risk in the secondary prevention of VTE in patients with thrombophilia, with a low hazard ratio for recurrent VTE calculated from cohort studies for DOAC vs warfarin, ranging from 0.3 to 0.75. We wish to highlight that treatment failure is greater in those with severe forms of protein S deficiency (below 20%) and possibly in antithrombin deficiency type II heparin-binding site homozygous Budapest 3. In summary, the current approach to using DOACs in patients with severe thrombophilia is dependent on clinical judgment and experience. Limited evidence suggests that for those with severe thrombophilias, full-dose DOACs have similar utility as vitamin K antagonists. We recommend caution in using low-dose DOACs due to lack of evidence. Ideally, large randomized multicenter studies are required to develop a reliable treatment algorithm., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. All rights reserved.)

Objective: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to maintain the circuit patency. However, the use of anticoagulation carries a risk of severe hemorrhage, necessitating rigorous monitoring. Activated clotting time (ACT) is a widely used monitoring tool; however, the evidence of its correlation with unfractionated heparin (UFH) infusion dose is limited. Here we aimed to analyze the correlation between ACT and UFH infusion during ECMO., Design: Systematic literature review and meta-analysis of correlation coefficients (Scopus and PubMed, up to July 13, 2024)., Prospero: CRD42023448888 SETTING: All retrospective and prospective studies PARTICIPANTS: Patients receiving ECMO support INTERVENTION: Anticoagulation monitoring during ECMO support MEASUREMENTS AND MAIN RESULTS: Nineteen studies were included in the analysis, and the meta-analysis encompassed 16 studies. The vast majority of studies (n = 15) found a weak correlation, and no study reported a strong correlation between ACT and UFH infusion dose. The meta-analysis (n = 12,625 samples) identified a weak correlation, with a pooled estimate of correlation coefficients of 0.132 (95% confidence interval 0.03-0.23). The most common adverse events were hemorrhage (pooled incidence, 45%) and thrombosis (30%), and 47% of the patients died during their hospital stay., Conclusions: Even though ACT is a widely used UFH monitoring tool in ECMO patients, our meta-analysis found a weak correlation between ACT and UFH infusion dose. New trials are needed to investigate the role of emerging tools and to clarify the most appropriate monitoring strategy for patients receiving ECMO support., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk., Methods: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years., Conclusion: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter., Trial Registration: ClinicalTrials.gov NCT05757869., Competing Interests: Disclosures SSJ reports consulting fees from Bristol Myers Squibb, ARTIS Ventures, and Broadview Ventures outside of the submitted work. KWM’s financial disclosures can be reviewed at http://med.stanford.edu/profiles/kenneth-mahaffey. KSP is a member of The Thrombosis Research Institute which has received institutional research grant support from Anthos Therapeutics and Bayer Pharmaceuticals. She has received honoraria from Element Science and Artivion, Inc. WS has received honoraria (>10K USD) from Daiichi Sankyo, Nippon Boehringer Ingelheim, and Pfizer Japan, and research grants (>50K USD) from Daiichi Sankyo and Nippon Boehringer Ingelheim. CTR reports Research Grants through Institution from: Athos, AstraZeneca, Daiichi Sankyo, Janssen and Novartis. Honoraria for scientific ad boards and consulting from: Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen and Pfizer. He is a member of The TIMI Study Group which has received institutional research grant support through Brigham and Women's Hospital from: Abbott, Abiomed, Inc, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis Pharmaceuticals, Inc, Janssen Research & Development, LLC, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Roche, Saghmos Therapeutics, Inc, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, Verve Therapeutics, Inc, Zora Biosciences. PRK reports consultancy from Anthos, J&J, BMS and Bayer. GS has received research grants from Amarin, AstraZeneca, and Sanofi; has participated in clinical trials, consulting, or speaking for Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Idorsia, Janssen, Novartis, Novo Nordisk, PhaseBio, Pfizer, and Sanofi; is a Senior Associate Editor at Circulation; and serves as the CMO for Bioquantis. RM reports institutional research payments from: Abbott, Affluent Medical, Alleviant Medical, Amgen, AstraZeneca, BAIM, Beth Israel Deaconess Medical Center, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CERC, Chiesi, Concept Medical, Daiichi Sankyo, Duke, Faraday, Idorsia, Janssen, MedAlliance, Medscape, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Pi-Cardia, Protembis, RM Global Bioaccess Fund Management, Sanofi; consultant to Affluent Medical, Boehringer Ingelheim, Chiesi USA, Cordis, Esperion Science/Innovative Biopharma, Gaffney Events, Educational Trust, Global Clinical Trial Partners, Ltd., IQVIA, Medscape/WebMD Global, NovoNordisk, PeerView Institute for Medical Education, TERUMO Europe N.V., Radcliffe and honoararia from AMA and ACC. SCJ has received research support from Jansen, BMS, and AstraZeneca. GJH reports personal honoraria outside the submitted work from the American Heart Association (Associate Editor, Circulation), Bristol Myers Squibb (Steering Committee, AXIOMATIC-SSP trial of milvexian [factor XIa inhibitor] for secondary stroke prevention) and Janssen (Co-chair, Executive Committee, Librexia Stroke trial of milvexian for secondary stroke prevention). RAH has received research grants/contracts from NHLBI (ISCHEMIA), Duke/PCORI (ADAPTABLE), Janssen (Factor Xia inhibitor), CSL (HDL), Baim Institute, UColorado, Harvard (BWH), and Merck; has served as a consultant/advisor for NHLBI (COVID/CONNECTS), Atropos Health, Bitterroot Bio, Bristol Myers Squibb, Bridge Bio, Chiesi, CSL Behring, Edwards Lifesciences Corp, Element Science, Foresight, Merck, and WebMD; and serves on the Board of Directors for AHA and Cytokinetics. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has Received research support from Novo Nordisk and Roche Diagnostics; has Served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Hanmi, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd., Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as Co-founder and nonexecutive director of Us2.ai. The remaining authors report no relevant disclosures or competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective:  We evaluated if venous thromboembolism (VTE) prophylaxis in the inpatient antepartum period was associated with wound hematomas, VTE occurrence, and other adverse outcomes., Study Design:  This study is a secondary analysis of a retrospective cohort of patients who delivered at University of Alabama at Birmingham (UAB). Patients receiving outpatient anticoagulation (AC) were excluded. We grouped patients into those who received inpatient antepartum prophylactic AC and those who did not. The primary outcome was wound hematomas from delivery to 6 weeks postpartum (PP). Secondary outcomes included VTE occurrence and select adverse outcomes, including other wound complications, unplanned procedures, mode of anesthesia, and intensive care unit (ICU) admission. Analyses were performed with no AC group as the reference. A sensitivity analysis excluding those who received inpatient PP AC was performed., Results:  Of 1,035 included patients, only 169 patients received inpatient prophylactic AC. They were older, had higher body mass indices, and more comorbidities. Patients receiving inpatient antepartum AC had higher wound hematomas (adjusted odds ratio [aOR] 23.81; 95% confidence interval [CI] 7.04-80.47). They had similar risk for developing VTE as the control group (aOR 2.68; 95% CI 0.19-37.49) but were more likely to have wound complications (aOR 2.36; 95% CI 1.24-4.47), maternal deaths ( p  < 0.05), and require PP ICU admission (aOR 13.38; 95% CI 4.79-37.35). When excluding those receiving any PP AC, there was no difference in bleeding complications between the two groups and VTE rates remained unchanged. Rates of maternal deaths and PP ICU admissions remained higher in those who received inpatient antepartum AC prophylaxis., Conclusion:  In this small cohort study, increased wound hematomas were found in those who received inpatient antepartum AC prophylaxis with no difference in VTE occurrence. While adverse events were increased in the inpatient AC group, this was mostly associated with PP AC prophylaxis. Larger studies should be conducted to describe the true benefits and risks of antepartum AC prophylaxis and determine efficacy of this widely used practice., Key Points: · Peripartum chemoprophylaxis is associated with increased wound hematomas.. · VTE is rare, despite its association with significant peripartum morbidity/mortality.. · Large studies are needed to guide practices that optimize the risk/benefit ratio of chemoprophylaxis.., Competing Interests: G.S. is an editor of the American Journal of Perinatology., (Thieme. All rights reserved.)

Extracorporeal membrane oxygenation (ECMO) support of critically ill pediatric patients is associated with increased risk of thromboembolic events, and unfractionated heparin is used commonly for anticoagulation. Given reports of acquired antithrombin (AT) deficiency in this patient population and associated concern for heparin resistance, AT activity measurement and off-label AT replacement have become common in pediatric ECMO centers despite limited optimal dosing regimens. We conducted a retrospective cohort study of pediatric ECMO patients (0 to <18 years) at a single academic center to characterize the pharmacokinetics (PK) of human plasma-derived AT. We demonstrated that a two-compartment turnover model appropriately described the PK of AT, and the parameter estimates for clearance, central volume, intercompartmental clearance, peripheral volume, and basal AT input under non-ECMO conditions were 0.338 dL/h/70 kg, 38.5 dL/70 kg, 1.16 dL/h/70 kg, 40.0 dL/70 kg, and 30.4 units/h/70 kg, respectively. Also, ECMO could reduce bioavailable AT by 50% resulting in 2-fold increase of clearance and volume of distribution. To prevent AT activity from falling below predetermined thresholds of 50% activity in neonates and 80% activity in older infants and children, we proposed potential replacement regimens for each age group, accompanied by therapeutic drug monitoring., (© 2024, The American College of Clinical Pharmacology.)

Introduction: Our retrospective study aimed at assessing safety of vascular closure devices (VCDs) used in a large single-centre Interventional Radiology (IR) department. Complication and deployment failure rates using collagen-based (Angio-seal) and suture-based (ProGlide) devices for common femoral artery haemostasis were compared., Materials and Methods: Data from VCDs deployed over a 6-year period were retrospectively analysed for patient age, procedure indication, puncture mode (antegrade/retrograde), sheath size, deployment failure and complications (haematoma, pseudoaneurysm formation, limb occlusion). Numerical and statistical analysis was undertaken., Results: Overall, 1321 common femoral artery punctures in 1217 patients were closed using VCDs. Failure rate using ProGlide was significantly higher when compared with Angio-seal ( P =<0.001) in sheath sizes ≤8 Fr. Heparin was not administered in embolisation procedures compared with angioplasty with or without stenting. Therefore, haematoma tended to occur more frequently following angioplasty without stenting ( P = 0.003) and angioplasty with stenting ( P = 0.001), when compared with embolisation. Deployment failure occurred more frequently when heparin was used during the procedure ( P = 0.005)., Conclusion: Although complications relating to sheath size are well established in the literature, there remains a paucity of data assessing the impact of procedure specific factors when comparing VCDs. Our study challenges that size is the sole determinant of VCD success and invites a more holistic view of VCD deployment strategies. This study advocates continued research into the nuances of other potential confounding variables to optimise patient outcomes., 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.

Purpose: To quantify baseline and longitudinal structural changes post-cessation in patients with pentosan polysulfate sodium retinopathy., Methods: This is a retrospective cohort study. Retinal thickness and volume of choroidal and hyperreflective retinal pigment epithelium excrescences were manually segmented from optical coherence tomography volume scans. Baseline measurements were compared against age-matched control subjects. Longitudinal measurements were performed on patients with follow-up data., Results: Twenty-four eyes of 13 patients were included. At baseline, the mean total retinal thickness was lower in the pentosan polysulfate sodium retinopathy cohort than in age- and sex-matched control subjects (269.1 µ m vs. 290.2 µ m, P = 0.006). The median (range) of follow-up was 18.6 (4.1-34.7) months, with the mean last follow-up of 35.2 months after cessation. During the follow-up period, the thickness of the retina decreased significantly by 11.3 µ m (CI: 16.8, 5.8) ( P < 0.001), with an annual mean decrease of 6.70 µ m. However, the mean hyperreflective retinal pigment epithelium excrescence volume did not change significantly ( P = 0.140) over the follow-up period., Conclusion: After pentosan polysulfate sodium discontinuation, although retinal pigment epithelium excrescence volume do not change significantly, there continues to be a progressive long-term thinning of the retina, which continues at a rate greater than that associated with normal aging. Consequently, long-term follow-up is suggested to monitor patients with pentosan polysulfate sodium retinopathy.

Background: Prophylactic dose of rivaroxaban is often used in treatment of isolated calf muscle vein thrombosis (ICMVT); nevertheless, its effect is less reported. This study aims to evaluate short-term outcomes in patients with ICMVT who received prophylactic dose of rivaroxaban or warfarin therapy., Methods: A retrospective analysis of 472 ICMVT patients who received 2 different treatment regimens was undertaken. Propensity score matching method was used to balance the confounding effect of baseline clinical data. Chi-squared test and logistic regression analysis were used to compare outcomes (venous thromboembolism events, bleeding events, complete clot resolution) according to the type of treatment regimens before and after propensity score matching. Univariate and multivariable analysis were used to investigate risk factors for incomplete clot resolution of ICMVT after propensity score matching., Results: 242 ICMVT patients received prophylactic dose of rivaroxaban (rivaroxaban group, RG), and 230 received warfarin (warfarin group, WG). After propensity score matching, 156 patients were included in each group; Venous thromboembolism (VTE) events occurred in 14 (9.0%) patients in the RG and 10 (6.4%) in the WG (P = 0.395); no major bleeding events occurred in each group, and clinically relevant nonmajor bleeding events occurred in 5 (3.2%) patients in the RG and 10 (6.4%) in the WG (P = 0.186); complete clot resolution at 3 months occurred in 80 (51.3%) patients in the RG and 100 (64.1%) in the WG (P = 0.022). Logistic regression analysis showed that there were no significant differences between RG and WG in VTE events (odds ratio 1.439, 95% confidence interval 0.619-3.347, P = 0.397) and clinically relevant nonmajor bleeding events (odds ratio 0.483, 95% confidence interval 0.161-1.449, P = 0.194); it revealed that complete clot resolution rate at 3 months was different in the 2 groups (odds ratio 0.589, 95% confidence interval 0.375-0.928, P = 0.022). Treatment regimens (prophylactic dose of rivaroxaban), thrombosis (maximum diameter >7 mm), and risk factors for VTE (nonsurgery risk factors, mainly referring to active malignancy) were risk factors for incomplete clot resolution of ICMVT (P < 0.05)., Conclusions: In this retrospective study with a short-term follow-up, ICMVT patients who received prophylactic dose of rivaroxaban had no significant differences in VTE and bleeding events compared to those who received warfarin therapy (the overall INR >2.0 for >50% of the time); but it was not conducive to complete clot resolution., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Treatment of isolated and non-obstructive atherosclerotic coronary artery ectasia (CAE) is still controversial., Aim: To assess the efficacy and safety of vitamin-K antagonist (VKA) versus dual antiplatelet (DAPT) therapy in management of patients with isolated and non-obstructive atherosclerotic CAE., Methods: We prospectively enrolled 79 patients diagnosed on elective coronary angiography to have either isolated CAE or non-obstructive atherosclerotic CAE. Patients were assigned in 1:1 pattern to receive either VKA (warfarin) or DAPT (aspirin plus clopidogrel). Patients were followed-up for nine-months. The primary endpoint was the cumulative events rate including acute coronary event, target vessel intervention, or cardiac death. Analysis of cumulative events at different time intervals, its individual components, and bleeding were considered secondary endpoints., Results: Cumulative events rate was 33%, with mortality rate of 2.5%. Both treatment groups showed comparable cumulative events during the nine-months follow-up duration. Nevertheless, Kaplan-Meier analysis beyond the first 3-months of follow-up showed significantly higher event-free survival among the VKA-group. Recurrent events (≥2) were significantly higher among the DAPT-group. Both groups showed no major bleeding events. Multivariable cox-regression analysis showed that presence of significant coronary tortuosity, use of DAPT in reference to VKA, and lower percent time in therapeutic range (%TTR) among those receiving VKA were significant independent predictors of clinical adverse events beyond the first 3-months of follow-up., Conclusion: Cumulative adverse events were comparable among both treatment groups for isolated non-obstructive CAE. However, adverse events were significantly more frequent in the DAPT-group beyond the first three months., Competing Interests: Declaration of competing interest No relationships that could be construed as a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Continuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children., Methods: The study involved children included in the EurAKId registry (NCT02960867), who underwent CKRT treatment. We analysed patient characteristics and CKRT parameters. The primary end point was mean circuit lifetime (MCL). Secondary end points were number of elective circuit changes and occurrence of dialysis-related complications., Results: The analysis was composed of 247 children who underwent 37,562 h of CKRT (median 78, IQR 37-165 h per patient). A total of 1357 circuits were utilised (3, IQR 2-6 per patient). MCL was longer in regional citrate anticoagulation (RCA), compared to heparin (HA) and no anticoagulation (NA) (42, IQR 32-58 h; 24, IQR 14-34 h; 18, IQR 12-24 h, respectively, p < 0.001). RCA was associated with longer MCL regardless of the patient's age or dialyser surface. In multivariate analysis, MCL correlated with dialyser surface area (beta = 0.14, p = 0.016), left internal jugular vein vascular access site (beta = -0.37, p = 0.027), and the use of HA (beta = -0.14, p = 0.038) or NA (beta = -0.37, p < 0.001) vs. RCA. RCA was associated with the highest ratio of elective circuit changes and the lowest incidence of complications., Conclusion: Anticoagulation modality, dialyser surface, and vascular access site influence MCL. RCA should be considered when choosing first-line anticoagulation for CKRT in children. Further efforts should focus on developing guidelines and clinical practice recommendations for paediatric CKRT., (© 2024. The Author(s).)

The clinical efficacy of tissue plasminogen activator (tPA) is limited by its lack of specific delivery, requiring large therapeutic doses that increase the risk of intracerebral hemorrhage, bleeding at the surgical site, and patient mortality after angioplasty. To address these limitations, this study aimed to develop a chitosan polysulfate (CsPs)-coated liposomal formulation for the sustained release of tPA. The CsPs-coated liposomes containing tPA (Liposome-tPA/CsPs) were fabricated using the thin-film hydration technique and their properties were compared to tPA-encapsulated nanoliposomes without a coating layer (Liposome-tPA). Liposome-tPA/CsPs showed a quasi-spherical morphology with a hydrodynamic diameter of 110 nm, while Liposome-tPA had a diameter of 80 nm. The thermal analysis showed that the degradation temperature and glass transition temperature (Tg) of Liposome-tPA/CsPs were higher than that of tPA alone, indicating improved temperature stability. The in vitro release study demonstrated a slow and sustained release of tPA from the Liposome-tPA/CsPs, with a concentration of 0.02 mg/ml at 1 h and 0.23 mg/ml at 180 h. The CsPs coating layer enhanced the antibacterial and antioxidant activity of the nanoliposomes. Liposome-tPA/CsPs exhibited higher cell viability compared to Liposome-tPA. It also achieved a higher percentage of thrombolysis, with complete clot dissolution observed after 3 h of treatment. These findings suggest that the Liposome-tPA/CsPs can be a promising approach to overcome the limitations associated with the systemic administration of tPA, potentially enhancing its clinical efficacy while reducing the risk of adverse events., 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. Published by Elsevier B.V.)

Background: Limited data exist on the safety and effectiveness of using direct oral anticoagulants (DOACs) in patients with atrial fibrillation aged 80 years or more with and without low bodyweight (LBW)., Objectives: We aimed to evaluate the safety and effectiveness of using DOACs in this population compared with warfarin., Methods: This retrospective active comparator new-user cohort study included veteran patients with atrial fibrillation who were newly initiated on either warfarin or DOACs between January 1, 2015, and January 1, 2021. The primary outcome was incidence of major bleeding and ischemic stroke. All outcomes were compared between treatment groups in 2 propensity score-matched cohorts of patients aged 80 years older with (AW) and without LBW (age-only cohort). Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs)., Results: Matched AW and age-only cohorts included 493 and 11 909 patients, respectively, in each of the DOAC and warfarin exposure groups. Greater than 90% were male, with a mean age of ∼87 years. The rate of major bleeding was lower in the DOAC group compared with warfarin in both the AW (aHR, 0.63; 95% CI, 0.46-0.87) and age-only cohorts (aHR, 0.58; 95% CI, 0.49-0.77). A significantly lower rate of ischemic stroke occurred in the DOAC group compared with warfarin in the AW cohort (aHR, 0.62; 95% CI, 0.45-0.84) and age-only cohort (aHR, 0.63; 95% CI, 0.58-0.68)., Conclusion: DOAC use was associated with lower risk of major bleeding and ischemic stroke compared with warfarin in patients aged 80 years or older with and without LBW., Competing Interests: Declaration of competing interests There are no competing interests to disclose. The results of this study do not represent the views of the federal government or the Veterans Health Administration., (Published by Elsevier Inc.)

Introduction: Individualized heparin and protamine management is increasingly used as a strategy to reduce coagulation activation and bleeding complications. While it is associated with increased heparin requirements during Cardiopulmonary Bypass (CPB), the impact on protamine administration remains controversial. We aim to investigate the effect of heparin level-guided monitoring on protamine dosing during cardiac surgery where low-anticoagulation protocols are implemented., Methods: This is a prospective, randomized, controlled trial. A total of 132 patients undergoing elective full-spectrum cardiac surgery with Minimal Invasive Extracorporeal Circulation (MiECC) were recruited. All patients were managed by the same anaesthetic, surgical and perfusion team. Patients were randomly allocated in two groups; the individualized heparin-protamine titration (IHPT) group and the conventional heparinization and reversal group by using ACT (cACT) with a 0.75:1, protamine: heparin ratio. Titration was accomplished with the Hepcon HMS Plus (Medtronic, Minneapolis, MN) system. The primary outcome of the study was the total protamine dose used. Secondary outcomes comprised of the total heparin dose, the percentage of patients achieving target ACT, 24-h transfusion requirements, postoperative bleeding, duration of mechanical ventilation, major morbidity and length of hospital stay. Patients in each group were divided in two subgroups according to the target ACT; those operated for coronary artery bypass grafting (CABG) using a target ACT >300 s and the rest (non-CABG) patients operated with a target ACT >400 s, respectively., Results: Protamine requirements were significantly reduced when IHPT was implemented; CABG (118 ± 24 mg vs 163 ± 61 mg; p < 0.001) and non-CABG cases (151 ± 46 mg vs 197 ± 45 mg; p < 0.001). Moreover, heparin requirements were significantly higher in the non-CABG subgroup managed with IHPT (34,539 ± 7658 IU vs 29,893 ± 9037 IU; p = 0.02). In overall, no significant differences were detected with respect to postoperative bleeding, transfusion of RBC or other blood products., Conclusions: Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery with MiECC implementing reduced anticoagulation strategy., Trial Registration: clinicaltrials.gov; NCT04215588., 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: Prevalence of bioprosthetic valve degeneration (BVD) is rising as the use of bioprosthetic aortic valves increases. Detecting early signs of BVD remains a challenge, with conventional imaging methods often failing to identify early deterioration stages. 18F-fuoride positron emission tomography (PET-CT) is an emerging technique that offers promising prospects to detect subclinical BVD. This study aimed to compare early PET parameters of fluoride uptake with echocardiographic hemodynamic parameters and compare outcomes according to anticoagulation in patients who received bioprosthetic valves., Methods: This is a sub-study of the ANTIPRO clinical trial, which involved patients undergoing surgical aortic valve replacement (SAVR) with a porcine bioprosthesis and randomized them into anticoagulated and non-anticoagulated groups. Hemodynamic changes were assessed by transthoracic echocardiography (TTE), while 18F-fluoride PET-CT quantified fluoride uptake and divided the patients in two groups: high-uptake and low-uptake. Mean and maximum gradients by TTE at three years were compared between the two uptake groups. Fluoride uptake was also compared between the anticoagulated and control groups., Results: We found no significant differences in transprosthetic gradients between high-uptake(21.4 ± 8.6 mmHg) and low-uptake(17.3 ± 11.2 mmHg.p = 0.244) PET-defined groups in this specific timeframe. Notably, anticoagulated patients exhibited significantly risk of higher fluoride uptake(OR = 4.34;95%CI:1.04-18.21.p = 0.045)., Conclusions: No association was found between fluoride uptake and hemodynamic evaluation. Anticoagulation was associated with higher fluoride uptake. These findings highlight the emerging role of PET-CT in studying bioprosthetic aortic valves and emphasize the need for extended follow-up to evaluate the impact of anticoagulation on valve degeneration., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation (AF) is associated with increased morbidity and mortality and exerts an increasingly significant burden on global healthcare resources, with its prevalence rising with an ageing population. Despite a substantial thromboembolic risk, particularly in the period immediately following diagnosis, oral anti-coagulation is frequently not initiated or is delayed. The aim of this study was to evaluate healthcare costs in people with AF, comparing those who were commenced on oral anti-coagulation in the immediate period following the index diagnosis date with those in whom initiation was late and those who never started anti-coagulation., Methods: This retrospective cost analysis used linked Scottish health data to identify adults newly diagnosed with AF between January 1st 2012 and April 30th 2019 with a baseline CHA 2 DS 2 -VASc score of ≥ 2. This AF population was sub-divided according to timing of the first prescription of oral anti-coagulant (OAC) during a 2-year follow-up period: never started (OAC never initiated), immediate OAC (OAC prescribed within 60 days of incident AF diagnosis), and delayed OAC (OAC prescribed more than 60 days after incident AF diagnosis). A two-part model was developed, adjusted for key covariates, including age, sex, and frailty, to estimate costs for inpatient admissions, outpatient care, prescriptions, and care home admissions, and overall costs., Results: Of an overall AF population of 54,385, 26,805 (49.3%) never commenced OAC, 7654 (14.1%) initiated an OAC late, and 19,926 (36.6%) were prescribed anti-coagulation immediately. The mean adjusted cost for the overall AF population was £7807 per person per year (unadjusted: £8491). Delayed OAC initiation was associated with the greatest adjusted estimated mean annual cost (unadjusted: £13,983; adjusted: £9763), compared to those that never started (unadjusted: £10,433; adjusted: £7981) and those that received an immediate OAC prescription (unadjusted: £3976; adjusted: £6621). Increasing frailty, mortality, and female sex were associated with greater healthcare costs., Conclusion: AF is associated with significant healthcare resource utilisation and costs, particularly in the context of delayed or non-initiation of anti-coagulation. Indeed, there exists substantial opportunity to improve the utilisation and prompt initiation in people newly diagnosed with AF in Scotland. Interventions to mitigate against the growing economic burden of AF should focus on reducing admissions to hospitals and care homes, which are the principal drivers of costs; prescriptions and outpatient appointments account for a relatively small proportion of overall costs for AF., (© 2024. The Author(s).)

The pediatric clinical development programs of the direct oral anticoagulants (DOACs) edoxaban, rivaroxaban, and dabigatran have recently been completed, with apixaban close to the finish line. One common pharmacokinetic (PK) characteristic of these four DOACs is that renal excretion contributes 27% or more in their elimination, resulting in age-dependent drug clearance in both pediatric and adult subjects. Several lessons have been learned from adult exposure matching and pediatric dose selection for DOACs. The main goal of this tutorial is to provide an informed perspective on pediatric dose selection for renally excreted drugs, using these four DOACs as case examples. This tutorial is organized into seven steps: (1) consideration of age-related differences in disease and response to treatment; (2) consideration of age-related differences in drug absorption, distribution, metabolism, and excretion; (3) selection of the reference adult population and exposure for pediatric exposure matching; (4) prediction of pediatric clearance and pediatric dose selection based on data from young adults; (5) conduct and design of efficient pediatric PK and pharmacodynamic (PD) studies that inform dose selection; (6) assessment of exposure matching and dose adjustment using population PK simulation; (7) evaluation of the need for dose adjustment in pediatric sub-populations., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Background: Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT., Methods: After institutional review board (IRB) approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. The demographic and clinical variables were collected as follows: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes., Results: 15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either noncardiac, nonvascular surgery, or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing), and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77 days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K ( ± 104.6 K) within an average of 2.3 days and 364K ( ± 273.9 K) within 30 days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30 days., Conclusions: Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The present research looked for ways to develop shielded nanoparticles (NPs)-drug transporters made of chitosan (CS) to enhance the bioavailability of edoxaban tosylate monohydrate (ETM) for oral administration by examining the correlation among design aspects and data from experiments using response surface methodology (RSM). ETM-loaded CS nanoparticles (ETM-CS-NPs) were developed using the ionic gelation of CS with tripolyphosphate (TPP). Utilising Zeta-sizer and scanning electron microscopy, the ETM-CS-NPs were evaluated for particle size (PS), zeta potential (ZP), surface morphology, polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Drug and polymer interactions in NPs were assessed using Fourier transform infra-red spectroscopy. The response surface approach and Design-Expert software optimised the ETM-CS-NPs. Using RSM, the effects of independent variables such as the amount of CS, the amount of TPP, and the amount of glacial acetic acid on PS, PDI and ZP were analysed. The optimal combination of PS (354.8 nm), PDI (0.509), ZP (43.7 + mV), % EE (70.3 ± 1.3) and % DL (9.1 ± 0.4) has been identified for the optimised ETM-CS-NPs. ETM-CS-NPs' anticoagulant activity was evaluated using activated partial thromboplastin time (aPTT), prothrombin time (PT) and thrombin time (TT) assays. In conclusion, a practical and consistent method has been established, and its application has been proven in vitro , indicating its utility for future studies of the biological distribution of ETM-CS-NPs in vivo for specific antithrombotic treatments.

Introduction: There are several types of surface treatments (coatings) aimed at improving the biocompatibility of cardiopulmonary bypass (CPB) circuit. Some coatings appear to require higher doses of heparin to maintain anticoagulation goals, and some of them might induce postoperative coagulopathy. In this study, we compared the amount of heparin required, postoperative bleeding, and inflammatory response according to three types of coatings., Method: We retrospectively included 300 consecutive adult patients who underwent cardiac surgery with CPB and received one of three coatings (Phisio®, Trillium®, and Xcoating™). Our primary objective was to compare, according to coating, the amount of heparin required to maintain an ACT > 400s during CPB. Our secondary objectives were to compare postoperative bleeding for 48 h and CRP rate., Results: Baseline characteristics were comparable between groups except for age and preoperative CRP. We did not find a significant difference between the 3 coatings regarding the amount of heparin reinjected. However, we found less postoperative bleeding with the Xcoating™ circuit compared to the Phisio® circuit (-149 mL [-289; -26.5]; p = 0.02) and a lower elevation of CRP with the Phisio® circuit (2.8 times higher than preoperative CRP) compared to Trillium® (4.9 times higher) and Xcoating™ (6.4 times higher); p < 10 -3 ., Conclusion: The choice of coating did not influence the amount of heparin required during CPB; however, the post-CPB inflammatory syndrome may be impacted by this choice., 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.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887-894., (© 2024 American Neurological Association.)

Elderly with multimorbidity are at higher risk of accumulating direct oral anticoagulants (DOAC). The presence of renal insufficiency, an extreme age or weight, a limited functional reserve, and a polypharmacy that may interact with DOAC, lead to an increased risk of bleeding. A medication review and an evaluation of DOAC exposure in this population could help identify this risk and better manage it. This evaluation is conducted in collaboration with coagulation experts through calibrated measurement of anti-Xa (rivarobaxan, apixaban and edoxaban), along with D-dimers measurement as a potential tool to assess thrombo-hemorrhagic risk. In the event of DOAC accumulation, experts could then propose personalized intervention, such as a dose reduction or a switch to another DOAC., Competing Interests: les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Aims/Background Femoral neck fractures in elderly patients carry a high risk of developing deep vein thrombosis (DVT) due to prolonged immobilization and surgical intervention. This study examines the effectiveness of combining intermittent pneumatic compression (IPC) with low-molecular-weight heparin (LMWH) for preventing DVT in elderly patients following femoral neck fracture surgery. Methods A total of 150 elderly patients with femoral neck fractures, admitted between January 2022 and January 2024, were retrospectively selected, and their clinical data were analyzed. Based on the treatment methods, the patients were divided into a control group (n = 71) and a study group (n = 79). The control group received LMWH treatment, while the study group received a combination of LMWH and IPC. The incidence of DVT, surgical outcomes, hip joint function, coagulation function indicators, hemodynamic indicators, and serum pro-inflammatory factors were compared between the two groups. Results The results showed that the incidence of DVT in the study group was lower than in the control group ( p = 0.017). There were no significant differences between the two groups in terms of intraoperative blood loss, postoperative drainage volume, or Harris scores ( p > 0.05). After the intervention, the study group demonstrated higher levels of average velocity (Va), peak blood flow velocity (Vp), and blood flow (BF) compared to the control group ( p < 0.05). Additionally, the activated partial thromboplastin time (APTT) and prothrombin time (PT) were longer, while the D-dimer (D-D) level was lower in the study group ( p < 0.05). The study group also exhibited lower levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) ( p < 0.05). Conclusion The results indicate that combining IPC with LMWH effectively reduces the incidence of postoperative DVT in elderly patients with femoral neck fractures, improves venous blood flow in the lower limbs, reduces vascular inflammation, and ensures safety.

Overview of: Rahman AA, Platt RW, Beradid S, et al. Concomitant use of selective serotonin reuptake inhibitors with oral anticoagulants and risk of major bleeding. JAMA Netw Open. 2024;7:e243208., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the past decades, there have been great advancements in the antithrombotic management of patients undergoing percutaneous interventions, but most of the available evidence derives from studies conducted in the setting of cardiac interventions. Antithrombotic treatment regimens used in patients undergoing percutaneous cardiac interventions, in particular coronary, are frequently extrapolated to patients undergoing noncardiac interventions. However, the differences in risk profile of the population treated and the types of interventions performed may translate into differences is the safety and efficacy associated with antithrombotic therapy. Noncardiac percutaneous interventions are commonly performed in patients at high bleeding risk, which may indeed impact outcomes, hence underscoring the importance of risk stratification to guide clinical decision-making processes. In this review, we appraise the available evidence on antithrombotic therapy in high-bleeding-risk patients undergoing noncardiac percutaneous interventions., Competing Interests: Funding Support and Author Disclosures Dr Andreotti has received speaker or consultancy fees from Amgen, Bayer, BMS/Pfizer, Daiichi-Sankyo, and Servier, outside the present work. Dr Capodanno has received personal honoraria from Novo Nordisk, Sanofi, and Terumo; payment her the institution from Meditronic, outside the present work. Dr Valgimigli has received personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals, Universität Basel/Department Klinische Forschung, Bristol Myers Squibb SA, Medscape, Biotronik, and Novartis, outside the submitted work; and grants from Terumo. Dr Mehran has received institutional research payments from Abbott, Abiomed, Affluent Medical, Alleviant Medical, Amgen, AM-Pharma, Applied Therapeutics, Arena, AstraZeneca, AtriCure Inc., Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Duke, Element Science, Faraday, Humacyte, Idorsia, I-Laser, Janssen, Magenta, MedAlliance, Medscape, Mediasphere, Medtelligence, Medtronic, MJH Healthcare, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Transverse Medical, Vivasure, and Zoll; has received personal fees from Affluent Medical, the Cardiovascular Research Foundation, Daiichi-Sankyo Brasil, E.R. Squibb & Sons, Esperion Science/Innovative Biopharma, Europa Group/Boston Scientific, Gaffney Events, Educational Trust, Ionis Pharmaceuticals, J-CalC, Novartis, Novo Nordisk, Vectura, VoxMedia, IQVIA, McVeigh Global, Overcome, Primer Healthcare of New Jersey, Radcliffe, SL Solutions, TARSUS Cardiology, and WebMD, outside the submitted work; owns equity (<1%) in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (via spouse); has received no fees for roles served with the American Medical Association (Scientific Advisory Board), Society for Cardiovascular Angiography and Interventions (Women in Innovations Committee Member); has served on the faculty of the Cardiovascular Research Foundation; and has received honoraria: JAMA Cardiology (Associate Editor), American College of Cardiology (Board of Trustees Member, Steering Committee Member Clinical Trials Research Program). Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura, outside the submitted work; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies., Design: Cross-sectional., Setting: European Medicines Association (EMA), US Food and Drug Administration (FDA), Health Canada and Australian Therapeutic Goods Administration (TGA)., Participants: Apixaban, dabigatran, edoxaban and rivaroxaban marketing authorisations., Outcome Measures: Concordance among regulatory agencies with respect to (1) premarket evidence used to establish efficacy and safety and (2) postmarket safety boxed warnings and postmarketing study requirements., Results: Apixaban, dabigatran and rivaroxaban were approved by each of the four regulatory agencies; edoxaban was only not approved by TGA. For premarket efficacy evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for three (75%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for four (100%) drugs and number of phase 2 trials for three (75%) drugs. For the premarket safety evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for two (50%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for three (75%) drugs and number of phase 2 trials for zero (0%) drugs. For postmarket safety information, FDA was the only agency that issued boxed warnings (for three (75%) drugs). Additionally, EMA and TGA required postmarketing studies (for four (100%) and two (50%) drugs, respectively), while FDA and Health Canada did not have any postmarketing requirements., Conclusions: There was a high degree of concordance in the phase 3 trial premarket evidence used to establish efficacy and safety of direct oral anticoagulant approvals across four major regulatory agencies, but discordance in the phase 2 trial premarket evidence used, as well as in postmarket safety boxed warnings and postmarketing study requirements. These discrepancies highlight opportunities for further harmonisation in the evaluation and regulation of medical products globally., Competing Interests: Competing interests: TZ have no potential competing interest to disclose. MM and JSR currently receive research support through Yale University from Arnold Ventures outside the submitted work. JSR reported receiving grants from the US Food and Drug Administration; Johnson and Johnson; Medical Device Innovation Consortium; Agency for Healthcare Research and Quality; National Heart, Lung, and Blood Institute and Arnold Ventures outside the submitted work. JSR is also an expert witness at the request of relator attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in September 2022., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report the case of a preterm infant presenting a thrombosis, discovered on ultrasound at 22 weeks of gestational age and confirmed at birth following additional examinations. We describe the anticoagulant treatment of this patient by intravenous enoxaparin, tinzaparin and rivaroxaban, from questioning to practice., Competing Interests: Competing interests: S P-L is an associate editor for EJHP., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

3D-printed dosage forms comprised of Carbopol and Eudragit were fabricated through semi-solid extrusion, combining Enoxaparin (Enox) and the permeation enhancer SNAC in a single-step process without subsequent post-processing. Inks were characterized using rheology and Fourier-transform infrared (FTIR) spectroscopy. The stability of Enox in the fabricated dosage forms was assessed by means of Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) analysis. In vitro release studies revealed the release of Enox in a sustained manner, whereas ex vivo experiments demonstrated the mucoadhesive properties of the 3D-printed dosage forms and their ability to enhance Enox permeability across intestinal mucosa. Cellular assays (CCK-8 assay) revealed a dose- and time-dependent response following incubation with the 3D-printed dosage forms. The encapsulation of SNAC in the 3D-printed dosage forms demonstrated their capacity to increase the transcellularly transport of macromolecule across Caco-2 monolayer in a reversible manner, as confirmed by Transepithelial Resistance (TEER) measurements., 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: The purpose of this study was to estimate the effect of remote nursing guidance based on WeChat platform for female patients receiving subcutaneous anticoagulation during the COVID-19 epidemic., Methods: Retrospective analysis of clinical data, including demographic data and anticoagulation complications, of 126 female patients who received subcutaneous anticoagulation therapy and received remote nursing guidance using WeChat platform in our hospital from January 2022 to December 2022. The Anti-Clot Treatment Scale (ACTS) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale were used to evaluate patients' satisfaction with anticoagulation and quality of life at the beginning of anticoagulation, half a month after anticoagulation, and after three months of anticoagulation., Results: In total, 126 patients were involved in this study, all of them were female, 115 cases were natural pregnancy, 11 cases were assisted reproduction. This study included seven cases of lower extremity deep vein thrombosis, 100 cases of hypercoagulable state, 10 cases of antiphospholipid syndrome, and eight cases of protein S deficiency, one case of hyperhomocysteinemia. During the follow-up period, four patients (3.17%) had subcutaneous injection complications, including three cases of subcutaneous hemorrhage and one case of liquid leakage. A total of 123 patients had completed the planned anticoagulation therapy or were receiving anticoagulation therapy as planned, and three patients did not receive anticoagulation therapy as planned (zero cases lost contact, two cases changed treatment units, and one case refused treatment). ACTS score (55.03 ± 1.73) and WHOQOL-BREF score (62.18 ± 3.17) after three months of anticoagulation, ACTS score (54.18 ± 1.20) and WHOQOL-BREF score (60.37 ± 2.25) after half a month of anticoagulation was significantly higher than the ACTS score (47.81 ± 1.69) and WHOQOL-BREF score (55.25 ± 1.85) at the beginning of anticoagulation, and the difference was statistically significant ( P value < 0.01)., Conclusions: During the COVID-19 pandemic, remote nursing instruction via the WeChat platform for female patients receiving subcutaneous anticoagulation can increase anticoagulation compliance, satisfaction, and quality of life., Competing Interests: The authors declare there are no competing interests., (©2024 Jiang et al.)

A female in her 60s was admitted via the emergency department following a respiratory collapse at home. She was profoundly hypoxic and hypertensive. For 1 week prior, she had been self-administering subcutaneous (SC) low molecular weight heparin (LMWH) for a small postoperative pulmonary embolism (PE) and reported worsening, self-resolving episodes of breathlessness 1 hour post-injection. Repeat imaging revealed a new small PE and blood tests showed a significant platelet drop. Her heparin-induced thrombocytopaenia (HIT) antibody test was positive. A diagnosis of HIT-associated anaphylactoid reaction was made. She was switched to a direct oral anticoagulant and fully recovered. This condition is well described, often presenting with profound respiratory compromise that can be misdiagnosed as 'massive PE'. A key differentiation is that there is often hypertension instead of hypotension. This case, however, is unusual as it was triggered by SC LMWH not intravenous heparin as previously described in the literature., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Extracorporeal line clotting during plasma exchange (PE) not only delays efficient treatment, but also cause great waste of nursing resources. There is a lack of comprehensive comparison of the efficacy and safety among different anticoagulation regimens in plasma exchange in literature., Methods: A systematic search was performed in EMBASE, MEDLINE via PubMed, Cochrane Central Library, and CNKI. Studies that had compared at least two anticoagulation regimens in PE were considered eligible. The anticoagulative efficacy outcome was assessed by the occurrence of extracorporeal circuit clotting. The safety outcome was assessed by the occurrence of bleeding events, post-treatment APTT values, and post-treatment platelets counts. The risk of bias was assessed by the AHRQ tool. Mean differences or standardized mean differences with 95% confidence intervals (CIs) of continuous variables and risk ratios (RRs) with 95% CIs of categorical variables were pooled using a random-effects or a fixed-effects model as appropriate., Results: In all, 7 studies with 1638 patients and 10951 sessions of PE treatment were included. Pooled results indicated the anticoagulative efficacy of UFH was better than that of saline flushing, yet did not differ with those of LMWH or RCA. Although the occurrence of bleeding events had no difference among different pairs of anticoagulation regimens, anticoagulation using UFH might lead to longer post-treatment APTT value and lower post-treatment platelet counts. Only one study was judged to have low risk of bias in each of the five domains in the AHRQ tool., Conclusions: The current anticoagulation regimens are generally effective and well tolerated in PE; however, the number of included studies was too limited to draw definitive conclusions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Venous thromboembolism (VTE) is a common complication in patients with brain tumors. The management of acute VTE is particularly challenging due to an elevated risk of intracranial hemorrhage (ICH). Risk of developing ICH on anticoagulation is influenced by a number of factors including tumor type, recent surgery, concomitant medications, platelet counts, and radiographic features. In patients with a heightened risk for ICH, the benefits of anticoagulation need to be balanced against a likelihood of developing major hemorrhagic complications. Management decisions include whether to administer anticoagulation, at what dose, placement of an inferior vena cava filter, monitoring for development of hemorrhage or progressive thrombus, and escalation of anticoagulant dose. This article discusses the complexities of treating acute VTE in patients with brain tumors and outlines treatment algorithms based on the presence or absence of ICH at the time of VTE diagnosis. Through case-based scenarios, we illustrate our approach to anticoagulation, emphasizing individualized risk assessments and evidence-based practices to optimize treatment outcomes while minimizing the risks of hemorrhagic events in patients with brain tumors., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Subdural haematomas (SDHs), acute or chronic, are common neurosurgical diagnoses. These problems can occur among patients requiring direct oral anticoagulation (DOAC) for atrial fibrillation. There are currently no guidelines regarding the optimal timing to resume anticoagulation for these patients after SDH. The objective of this study is to evaluate the feasibility of conducting a future large randomised controlled trial (RCT) evaluating the safety and efficacy of resuming DOACs early (ie, at 30 days) vs late (ie, at 3 months) for patients with atrial fibrillation following diagnosis of SDH., Methods and Analysis: This is a pilot, open-label, multicentre RCT that will enrol adults with newly diagnosed acute or chronic SDH with or without other intracranial bleeding who were receiving therapeutic anticoagulation with a DOAC as stroke prophylaxis for atrial fibrillation. Patients will be randomly allocated to resume a DOAC at standard dosing starting either days 30+7 or days 90±14. The primary outcomes for the pilot RCT are recruitment rate, protocol adherence and patient compliance with the randomly allocated interventions. Secondary outcomes are patient functional outcomes and safety and effectiveness outcomes, which will comprise key endpoints for the future planned RCT. This pilot RCT will provide important data to inform the feasibility of conducting a future, large RCT of early versus late resumption of DOACs for atrial fibrillation stroke prophylaxis in patients newly diagnosed with SDH. The future RCT will help inform management of a commonly encountered clinical dilemma with high associated morbidity and mortality., Ethics and Dissemination: This study has been approved by the research ethics board of record. It will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. Informed consent will be obtained from eligible patients or substitute decision-makers. Data from this study will inform the design of future, larger RCTs., Trial Registration Number: NCT05472766., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Warfarin dose requirements are highly variable because of clinical and genetic factors. Although genetic variants influencing warfarin dose have been identified in European and East Asian populations, more work is needed to identify African-specific genetic variants to help optimize warfarin dosing. We performed genome-wide association studies (GWASs) in 4 African cohorts from Uganda, South Africa, and Zimbabwe, totaling 989 warfarin-treated participants who reached stable dose and had international normalized ratios within therapeutic ranges. We also included 2 African American cohorts recruited by the International Warfarin Pharmacogenetics Consortium (n = 316) and the University of Alabama at Birmingham (n = 199). After the GWAS, we performed standard error-weighted meta-analyses and then conducted stepwise conditional analyses to account for known loci in chromosomes 10 and 16. The genome-wide significance threshold was set at P < 5 × 10-8. The meta-analysis, comprising 1504 participants, identified 242 significant SNPs across 3 genomic loci, with 99.6% of these located within known loci on chromosomes 10 (top SNP: rs58800757, P = 4.27 × 10-13) and 16 (top SNP: rs9925964, P = 9.97 × 10-16). Adjustment for the VKORC1 SNP -1639G>A revealed an additional locus on chromosome 2 (top SNPs rs116057875/rs115254730/rs115240773, P = 3.64 × 10-8), implicating the MALL gene, that could indirectly influence warfarin response through interactions with caveolin-1. In conclusion, we reaffirmed the importance of CYP2C9 and VKORC1 in influencing warfarin dose requirements, and identified a new locus (MALL), that still requires direct evidence of biological plausibility., (© 2024 by The American Society of Hematology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Various oral anticoagulants have been used for stroke prevention in older patients with atrial fibrillation (AF). However, the optimal anticoagulants for stroke prevention has not yet been developed. We performed a systematic review and network meta-analysis to determine the optimal instructions., Methods: We searched for randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Library without restriction for publication date or language at January 2024. Any RCTs that compared the effectiveness of a direct oral anticoagulant and a vitamin K antagonist (VKA) for stroke prevention in older patients with AF were included in this network meta-analysis. The Bayesian network meta-analysis used a random effects model and surface under the cumulative ranking curve analysis to rank results. All analyses were done using R software with gemtc package, with statistical significance set at P < .05., Results: We included 7 RCTs (79,003 patients) comparing 8 different instructions including Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, Edoxaban 60 mg, Rivaroxaban 15 mg, Rivaroxaban 20 mg, and VKA. Apixaban 5 mg, Dabigatran 110 mg, and Dabigatran 150 mg was more effective than the VKA for reducing stroke or systemic embolism risks, and the difference was statistically significant (P < .05). Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, and Edoxaban 60 mg was associated with a reduction of the intracranial hemorrhage rate than the VKA (P < .05). The surface under the cumulative ranking curve shows that Dabigatran 110 mg ranked first for reducing stroke or systemic embolism risks. Edoxaban 60 mg ranked first for major bleeding. Dabigatran 110 mg ranked first for intracranial hemorrhage. Apixaban 5 mg ranked first for all bleeding events., Conclusions: Direct oral anticoagulants were found to have lower rates of thromboembolic events compared to VKAs in older patients with AF. Apixaban 5 mg, Dabigatran 110 mg, Dabigatran 150 mg, Edoxaban 30 mg, and Edoxaban 60 mg were also associated with a reduction of intracranial hemorrhage than VKA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation. We investigated the impact of UFH dose during ECMO therapy at the coagulation-inflammation interface level, focusing on complement activation and changes in circulating large EV (lEV) subsets. In a post hoc analysis of a multicenter randomized controlled trial comparing two anticoagulation management algorithms, we examined lEV levels and complement activation in 23 veno-venous-ECMO patients stratified by UFH dose. Blood samples were collected at different time points and grouped into three phases of ECMO therapy: initiation (day 1), mid (days 3-4), and late (days 6-7). Immunoassays detected complement activation, and flow cytometry analyzed lEV populations with an emphasis on mitochondria-carrying subsets. Patients receiving <15 IU/kg/h UFH exhibited higher levels of the complement activation product C5a and soluble terminal complement complex (sC5b-9). Lower UFH doses were linked to increased endothelial-derived lEVs, while higher doses were associated with elevated RBC-derived and mitochondria-positive lEVs. Our findings suggest the potential theranostic relevance of EV detection at the coagulation-inflammation interface. Further research is needed to standardize EV detection methods and validate these findings in larger ECMO patient cohorts.

Venous thromboembolism (VTE) is a serious health condition and represents an important cause of morbidity and, in some cases, mortality due to the lack of effective treatment options. According to the Centers for Disease Control and Prevention, 3 out of 10 people with VTE will have recurrence of a clotting event within ten years, presenting a significant unmet medical need. For some VTE patients, symptoms can last longer and have a higher than average risk of serious complications; in contrast, others may experience complications arising from insufficient therapies. People with VTE are initially treated with anticoagulants to prevent conditions such as stroke and to reduce the recurrence of VTE. However, thrombolytic therapy is used for people with pulmonary embolism (PE) experiencing low blood pressure or in severe cases of DVT. New drugs are under development, with the aim to ensure they are safe and effective, and may provide an additional option for the treatment of VTE. In this review, we summarize all ongoing trials evaluating anticoagulant interventions in VTE listed in clinicaltrials.gov, clarifying their underlying mechanisms and evaluating whether they prevent the progression of DVT to PE and recurrence of thrombosis. Moreover, this review summarizes the available evidence that supports the use of antiplatelet therapy for VTE. Since thrombolytic agents would cause off-target effects, targeted drug delivery platforms are used to develop various therapeutics for thrombotic diseases. We discuss the recent advances achieved with thrombus-targeting nanocarriers as well as the major challenges associated with the use of nanoparticle-based therapeutics.

Background: In the BRIGHT-4 (Bivalirudin With Prolonged Full-Dose Infusion During Primary PCI Versus Heparin Trial-4), anticoagulation with bivalirudin plus a 2- to 4-hour high-dose infusion after percutaneous coronary intervention (PCI) reduced all-cause mortality and bleeding without increasing reinfarction or stent thrombosis compared with heparin alone in patients with ST-segment elevation myocardial infarction (STEMI). These findings require external validation., Objectives: This study sought to determine outcomes of bivalirudin vs heparin anticoagulation during PCI in STEMI., Methods: We performed an individual-patient-data meta-analysis of all large randomized trials of bivalirudin vs heparin in STEMI patients undergoing primary PCI performed before BRIGHT-4. The primary endpoint was all-cause mortality., Results: Six trials randomizing 15,254 patients were included. Pooled across all regimens of bivalirudin and glycoprotein IIb/IIIa inhibitor (GPI) use, bivalirudin reduced 30-day all-cause mortality (2.5% vs 2.9%; adjusted OR: 0.78; 95% CI: 0.62-0.99), cardiac mortality (adjusted OR: 0.69; 95% CI: 0.54-0.88), and major bleeding (adjusted OR: 0.53; 95% CI: 0.44-0.64) but increased reinfarction (adjusted OR: 1.30; 95% CI: 1.02-1.65) and stent thrombosis (adjusted OR: 1.43; 95% CI: 1.05-1.93) compared with heparin. In 4 trials in which 6,244 patients were randomized to bivalirudin plus a high-dose post-PCI infusion vs heparin without planned GPI use (the BRIGHT-4 regimens), 30-day all-cause mortality occurred in 1.8% vs 2.9% of patients, respectively (adjusted OR: 0.74; 95% CI: 0.48-1.12), and bivalirudin reduced cardiac mortality (adjusted OR: 0.62; 95% CI: 0.39-0.97) and major bleeding (adjusted OR: 0.49; 95% CI: 0.35-0.70), with similar rates of reinfarction (adjusted OR: 0.89; 95% CI: 0.58-1.38) and stent thrombosis (adjusted OR: 0.80; 95% CI: 0.41-1.57)., Conclusions: In STEMI patients undergoing primary PCI, bivalirudin with a 2- to 4-hour post-PCI high-dose infusion reduced cardiac mortality and major bleeding without an increase in ischemic events compared with heparin monotherapy with provisional GPI use, confirming the BRIGHT-4 results., Competing Interests: Funding Support and Author Disclosures The present study was supported by a research grant from The Medicines Company to the Cardiovascular Research Foundation. Dr Bikdeli is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and a Career Development Award from the American Heart Association and VIVA Physicians (#938814). Dr Stone has received speaker honoraria from Medtronic, Pulnovo, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Valgimigli has received grants from Terumo; and has received personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CorFlow, Idorsia Pharmaceuticals, Universität Basel Dept Klinische Forschung, Bristol Myers Squibb SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Erlinge has received honoraria for advisory boards from AstraZeneca, Bayer, Chiesi, and Sanofi; and has received speaker honoraria from Bayer, AZ, Novartis, and Chiesi. Dr Steg has received research grants from Amarin, AstraZeneca, Bayer, Sanofi, and Servier; and has received honoraria for clinical trials (serving on the steering committee, clinical endpoint committee, data and safety monitoring committee) from Amarin, AstraZeneca, Bayer, Bristol Myers Squibb, Idorsia, Novartis, PhaseBio, Pfizer, Sanofi, Servier, and The Medicines Company; has received fees for consulting or speaking from Amarin, Amgen, BMS, Novo Nordisk, and Regeneron; and is a Senior Associate Editor at Circulation. Dr James’s employer has received research grants from Novartis, Amgen, Janssen, Bayer, AstraZeneca, and Infraredex. Dr Mehran has received institutional research funding from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca, AtriCure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia, Janssen, Magenta, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, RM Global, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; holds equity in Applied Therapeutics, Elixir Medical, and Stel; has served on scientific advisory boards for the AMA, ACC (BOT member), and SCAI (Women in Innovations Committee member); has served as an associate editor of JAMA; is an unpaid member of the faculty of CRF; and her spouse has received personal fees from ControlRad. Dr Bikdeli has been a consulting expert, on behalf of the plaintiff, for litigation related to 2 brand models of IVC filters. 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: Most evidence for anticoagulation in aortic bioprosthesis is centered on embolic events, bleeding and re-intervention risk. The effect of anticoagulation on hemodynamics has not been previously assessed. Our hypothesis was that patients with anticoagulation (AC) early after aortic valve replacement (AVR) with porcine bioprosthesis have better hemodynamics at 3 years of follow-up., Methods: This is a follow-up evaluation of the ANTIPRO trial. All patients undergoing AVR with porcine bioprosthesis were consecutively recruited. The AC group received warfarin+aspirin and the non-AC(control) only aspirin. The primary outcome was mean gradient after 3 years of AVR and change in New York Heart Association (NYHA) class. Secondary outcomes were major and minor bleeding and embolic events., Results: Of 140 participants in the study, 71 were assigned to the AC group and 69 to the control group. Mean age of the overall population was 72.4(SD: 7.1) years. Global euroSCORE was 7.65(SD: 5.73). At 3 years the mean gradient was similar between both groups (19.4(SD: 9.6 mmHg) and 18.6(SD: 8.2 mmHg) in the control and AC group respectively, p = 0.7). No differences in functional class at 3 years were found among groups. No differences were found among groups in the secondary outcomes., Conclusions: The addition of 3 months of oral anticoagulation to anti-aggregation treatment did not affect bioprosthetic hemodynamics nor functional class at years after AVR., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Current guidelines recommend direct oral anticoagulants (DOACs) and warfarin for patients with atrial fibrillation (AF) who have a bioprosthetic valve (BPV). However, the data related to elderly patients (aged ≥80 years) with BPV replacement and AF are limited., Methods: This post-hoc subgroup analysis of a BPV-AF Registry enrolled 752 patients with BPV replacement and AF. The primary net outcome was a composite of cardiac death, stroke, systemic embolism, major bleeding, and cardiovascular events., Results: Among 752 patients, 429 (57%) patients were ≥ 80 and 323 (43%) were < 80 years old. The higher risk in patients aged ≥80 than <80 years was significant for the net outcome (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.31-3.17; P = 0.001). After adjustment for confounders, there was no statistically significant difference between warfarin (reference) and DOAC users in the risk of net outcomes (adjusted HR, 1.26; 95% CI, 0.71-2.24; P = 0.44), stroke and systemic embolism (adjusted HR, 2.01; 95% CI, 0.48-8.38; P = 0.34), and major bleeding (adjusted HR, 0.73; 95% CI, 0.11-4.98; P = 0.75) in patients aged ≥80 years old as well as those aged <80 years. Among 489 warfarin users, the cumulative incidence of net outcomes tended to be higher in patients aged ≥80 than <80 years (12.2% vs. 5.7% at 1 year, log-rank P = 0.002). Among 263 DOAC users, however, it was similar between patients aged ≥80 and < 80 years., Conclusions: The present study demonstrated that DOAC showed similar efficacy and safety compared with warfarin even in elderly patients aged ≥80 years with BPV replacement and AF., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Although anticoagulation remains the cornerstone treatment for patients with acute pulmonary embolism (PE), catheter-directed therapy (CDT) has generated great interest as an adjunctive option for those presenting with hemodynamic decompensation or high risk for deterioration and in whom systemic thrombolysis has failed or is contraindicated. However, randomized controlled data supporting the efficacy and safety of CDT in addition to antithrombotic therapy in patients with high-risk and intermediate- to high-risk PE compared with anticoagulation and systemic thrombolysis alone are lacking. This paucity of high-quality data hampers guideline recommendations regarding the optimal therapeutic approach in such patients with PE. The aim of the present paper is to critically appraise the current evidence for CDT in patients with high-risk and intermediate- to high-risk PE and to highlight major areas of innovation in the recent literature. In addition, the authors describe unmet clinical and research needs, potential strategies to resolve these knowledge gaps, and pathways for device selection., Competing Interests: Funding Support and Author Disclosures Dr Piazza has received research grants from Bristol Myers Squibb/Pfizer, Janssen, Alexion, Bayer, Amgen, Boston Scientific, Esperion, and 1R01HL164717-01; and is an adviser to Boston Scientific, Amgen, BCRI, PERC, NAMSA, Bristol Myers Squibb, Janssen, and Regeneron. Dr Sharp is a consultant to Medtronic, Boston Scientific, Philips, Penumbra, and Recor Medical; and has stock options with Althea Medical. 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.)

Rationale: Extracorporeal membrane oxygenation (ECMO) technology in the field of intense care for children in China has developed rapidly, and it has become a key strategy for the rescue treatment of critically ill children and an advanced extracorporeal life support system. Compared with adults and children, neonatal respiratory disease with ECMO support has the best prognosis, with an average survival rate of 74%. Bleeding and thrombotic events during ECMO are common, morbid, and potentially lethal. Therefore, how to balance the coagulation state is the key to ECMO management., Patient Concerns: A full-term male infant (2h 5min) was hospitalized for respiratory distress and cyanosis. With a history of premature rupture of membranes (>7 hours) and a birth weight of 3000 g, the patient had Apgar scores of 7, 8, and 9 at 1, 5, and 10 minutes, respectively., Diagnoses: This infant has the indication of extracorporeal membrane lung support. After full communication, venoarterial-ECMO was performed, and intravenous infusion of heparin was used for anticoagulation management., Interventions: We encountered an unreliable heparin monitoring in an infant on ECMO, which considered as heparin resistance. Subsequently, we switched the anticoagulant from heparin to bivalirudin and managed by using multiple laboratory tests including activated clotting time (ACT) and activated partial thromboplastin time. The phenomenon of inconsistent monitoring results occurred later. To help the clinic to adjust the anticoagulation dose accurately, we adopted additional tests such as thrombin-antithrombin complex (TAT) and fibrin/fibrinogen degradation products and applied comparison of thrombela stogram (TEG)-ACT with anticoagulated specimens and bedside non-anticoagulated ACT, then recommended clinicians to use activated partial thromboplastin time combined with TAT., Outcomes: In collaboration with other symptomatic supportive treatments, the ECMO flow was gradually reduced, the respiratory and circulatory functions were stable after reducing the flow rate, there was no bleeding tendency, and the ECMO was finally evacuated., Lessons: Due to the unique physiological characteristics of newborns, the hemostatic changes differ significantly from those in adults. Precise monitoring of anticoagulation becomes a critical and challenging task. Bivalirudin can be effectively used for anticoagulation management in neonatal ECMO; however, due to its unique characteristics, precise dose adjustment poses a challenge. Selecting the optimal laboratory monitoring indicators is crucial in this regard. In some cases, bedside ACT may not be the optimal anticoagulation monitoring parameter, and when necessary, comparative analysis can be conducted using anticoagulant-sample ACTs such as thrombela stogram-ACT. Traditional markers such as D-dimer/fibrinogen degradation products and newer indicators like TAT can reflect the activation of coagulation and assist in monitoring the anticoagulation effect, especially when there is conflicting information among the monitoring parameters., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)