Antiplatelet agents, particularly P2Y12 receptor inhibitors, are critical medicines in the prevention and treatment of thrombotic diseases in the clinic. However, their long-term use introduces a significant risk of bleeding in patients with cardiovascular diseases. Whether the bleeding is caused by the drug itself or due to surgical procedures or trauma, the need to rapidly reverse the effects of antiplatelet agents in the circulation is essential; however, no such agents are currently available. To address this need, here we describe a strategy that uses cell-membrane-wrapped nanoparticles (CM-NPs) for the rapid reversal of P2Y12 inhibitors. CM-NPs are fabricated with membranes derived from 293T cells genetically engineered to overexpress the P2Y12 receptor. Our findings support the potential of CM-NPs as a strategy for managing bleeding complications associated with P2Y12 receptor inhibitors, offering an approach to improve the safety in the use of these drugs in clinical settings.

UNASSIGNED: Small reference vessel diameters (RVDs) are a predictor of ischemic events after coronary stenting. Among patients at high bleeding risk (HBR) precluding long-term dual antiplatelet therapy (DAPT), those with small vessel disease (SVD) constitute an especially high-risk subgroup. Here, we evaluated the results of a durable-polymer, coronary zotarolimus-eluting stent (ZES) for the treatment of patients with SVD at HBR with 1-month DAPT.
UNASSIGNED: In the prospective, multicenter Onyx ONE (One-Month DAPT) Clear study, 1506 patients at HBR treated with a ZES that discontinued DAPT at 30 days were included. The clinical outcomes of patients undergoing treatment of lesions with an RVD of ≤2.5 mm (SVD group, as determined by the angiographic core laboratory) were compared with patients without SVD. The primary end point was the composite of cardiac death or myocardial infarction between 1 and 12 months.
UNASSIGNED: Small vessel diameter treatment was performed in 489 (32.5%) patients. Patients with SVD were more likely to be women, have undergone a previous percutaneous intervention, and have multivessel coronary artery disease than patients without SVD. There were no significant differences in lesion, device, or procedural success between the groups. The Kaplan-Meier rate estimate of the primary end point was 8.5% and 6.8% in patients with SVD and those without SVD, respectively (P = .425). No significant differences were found in any secondary end point. The Kaplan-Meier rate of stent thrombosis was 0.6% and 0.8% in patients with SVD and those without SVD, respectively (P = .50).
UNASSIGNED: Among patients at HBR treated with a ZES and 1-month DAPT, those with SVD had favorable 12-month ischemic and bleeding outcomes, which were comparable with those of patients with larger caliber vessels.

Background/Objectives: The need to determine the safest duration of dual antiplatelet therapy duration after elective angioplasty to reduce bleeding events without an adverse effect on major adverse cardiovascular events (MACE) remains a challenge. Methods: In this investigator-initiated, single-centre cohort study, we identified all patients who underwent PCI for de novo coronary disease for stable angina between January 2015 and November 2019. We compared 1-month and 12-month durations of dual antiplatelet therapy (DAPT) to determine if there was any difference in the primary outcome of major bleeding. The secondary outcome was a patient-oriented composite endpoint of all-cause mortality; any myocardial infarction, stroke, or revascularisation; and the individual components of this composite endpoint. Data were analysed using Cox regression models and cumulative hazard plots. Results: A total of 1025 patients were analysed, of which 340 received 1 month of DAPT and 685 received 12 months of DAPT. There was no difference in major bleeding between the two groups (2.6% vs. 2.5% respectively). On univariable cox regression analysis, no characteristics were predictors of major bleeding. A proportion of 99.7% of patients in the 1-month DAPT arm were treated with a DCB strategy, whilst 93% in the 12-month DAPT group were treated with a DES. There was no difference between the two groups with regards to the composite patient-oriented MACE (11% vs. 12%, respectively) or any individual component of this. These results were unchanged after propensity score matched analysis. Conclusions: A 1-month duration of DAPT, for which 99.7% of patients were treated with a DCB strategy, appears safe and effective when compared with a 12-month duration of DAPT with no difference in major bleeding or MACE.

Several studies in literature have shown that 90% of emboli related to non-valvular atrial fibrillation originate from left atrial appendage. Percutaneous closure or surgical exclusion of left atrial appendage in patients with high bleeding and high cardioembolic risk is currently a well established procedure in literature, clinical practice and guidelines. Knowledge of different techniques of left atrial appendage closure is necessary to individualize the procedure according to the patient anatomy and pre-procedural imaging evaluations. In this review the authors will evaluate different left atrial appendage closure systems and the different pre and intra procedural imaging methods.

Cancer-associated thrombosis (CAT) is a devastating complication of cancer that can significantly impact a patient\'s health and life. The incidence of CAT is approximately 20%, and 1 in 5 cancer patients will develop CAT annually. Indeed, CAT can promote pulmonary embolism and deep vein thrombosis, leading to increased morbidity and mortality that dramatically impact survival. CAT can also provoke delay or discontinuation of anticancer treatment, which may result in a lack of treatment efficacy and high costs for patients, institutions, and society. Current guidelines advocate direct oral anticoagulants (DOACs) as the first-line anticoagulant option in CAT. Compared to low-molecular-weight-heparins (LMWHs), DOACs are advantageous in that they typically have an oral route of administration, do not require laboratory monitoring, and have a more predictable anticoagulant effect. However, in patients with thrombocytopenia, renal failure, or those receiving anticancer regimens with potential for drug-drug interactions, LMWH is still the mainstay of care. The main limitation of current anticoagulant agents is related to bleeding risk (BR), both for DOACs and LMWHs. Specifically, DOACs have been associated with high BR in gastrointestinal and genitourinary cancers. In this challenging scenario, abelacimab, an anti-factor XI agent, could represent a viable option in the management of CAT due to its \"hemostasis sparing\" effect. The safe profile of abelacimab could be useful in patients with active malignancy and CAT, as long-term anticoagulant therapy is often required. Two ongoing international phase III trials (Aster and Magnolia) compare abelacimab with the standard of care (i.e., apixaban in patients with CAT and dalteparin in those with CAT and high BR, respectively). Abelacimab is a new and attractive anticoagulant for the management of CAT, especially in the insidious and critical scenario of active cancer patients with venous thromboembolism and high BR. The aim of this narrative review is to discuss the updated evidence on the performance of DOACs and LMWHs in the treatment of CAT and to focus on the potential role of abelacimab in CAT and its promising associated clinical trials.

BACKGROUND: A percutaneous kidney biopsy (PKB) allows nephrologists to make informed decisions for treating various kidney diseases; however, the risk of bleeding complications should be considered, given the vascularity of the kidney. Many studies have reported risk factors for bleeding events after a PKB. However, while urinary N-acetyl-β-D-glucosaminidase (NAG) is a useful biomarker of kidney disease severity, little is known about whether or not urinary NAG is related to the bleeding risk.
METHODS: Medical records of patients who underwent a PKB at the National Defense Medical College Hospital between October 2018 and October 2023 were retrospectively studied. Hemoglobin (Hb) loss ≥ 1 g/dL was defined as a bleeding event.
RESULTS: Of the 213 patients, 110 (51.6%) were men, and the median age was 56 years old (interquartile range 40-71). The most frequent diagnosis on a PKB was IgA nephropathy (N = 72; 34.0%). Fifty-four patients (25.3%) experienced Hb loss ≥ 1 g/dL after a PKB, and urinary NAG/Cr levels before the biopsy were able to predict a bleeding event, with an area under the receiver operating characteristic curve of 0.65 (p = 0.005). Using the optimal cutoff value of 35 U/gCr, urinary NAG/Cr was found to be an independent risk factor by multiple logistic regression analysis (odds ratio 3.21, 95% confidence interval 1.42-7.27, p = 0.005). Even after adjusting for previously-reported risk factors, the elevated urinary NAG/Cr ratio remained a statistically significant variable. Compared with the pathological findings, only the severity of multilayered elastic laminae of the small muscular artery was associated with both urinary NAG/Cr levels (p = 0.008) and bleeding events (p = 0.03).
CONCLUSIONS: Urinary NAG successfully predicted not only the severity of kidney disorders but also bleeding events after a PKB. Arteriosclerosis in the kidneys may be the mechanism underlying these increased bleeding events.

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

BACKGROUND: Patients undergoing left atrial appendage occlusion (LAAO) are at increased risk for bleeding or thromboembolic events. Concurrently, biomarkers are of growing importance in risk stratification for atrial fibrillation patients. We aimed to evaluate the association of hematological markers and clinical characteristics with the occurrence of thromboembolic and bleeding events following LAAO.
METHODS: Seven implanting centers retrospectively gathered data on hematological markers (i.e., platelet count [PC], mean platelet volume [MPV], and fibrinogen) prior to LAAO. Prespecified thromboembolic and major bleeding outcomes were collected and the association with pre-procedural hematological markers and clinical characteristics was evaluated using Cox regression analysis.
RESULTS: In total, 1,315 patients were included (74 ± 9 years, 36% female, CHA2DS2-VASc 4.3 ± 1.5, HAS-BLED 3.3 ± 1.1). Over a total follow-up duration of 2,682 patient years, 77 thromboembolic events and 107 major bleeding events occurred after LAAO. Baseline PC was the only biomarker showing a signal for a relation to thromboembolic events (HR 1.18, 95% CI: 1.00-1.39) per 50*109 increment, p = 0.056). Thrombotic event rates, including device-related thrombus, increased within higher PC quartiles. Thromboembolism was associated with age (HR 1.05, 95% CI: 1.00-1.10, per year increase) and prior thromboembolism (HR 2.08, 95% CI: 1.07-4.03), but with none of the biomarkers in multivariate analysis. No association of any of the hematological markers with major bleeding was observed. Major bleeding following LAAO was associated with prior major bleeding (HR 5.27, 95% CI: 2.71-10.22), renal disease (HR 1.93, 95% CI: 1.17-3.18), and discharge on dual antiplatelet therapy (DAPT) (HR 1.71, 95% CI: 1.05-2.77).
CONCLUSIONS: Most thrombotic events occurred in the highest PC quartile, but no association of any of the hematological markers with thromboembolism or major bleeding was observed in our analysis. In multivariate analysis, older age and prior thromboembolism were associated with thromboembolism. Prior major bleeding, renal disease and discharge on DAPT were multivariate predictors of major bleeding after LAAO.

Heart failure is hemodynamically characterized as congestion and/or end-organ hypoperfusion, and is associated with increased morbidity and mortality. Underlying pathophysiology, such as neuro-hormonal activation, exacerbates heart failure and leads to functional deterioration of other organs. We have been conducting clinical research to study the pathophysiology of heart failure and discover prognostic factors. In this review article, we report the results and implications of our clinical research on heart failure.

BACKGROUND: The age of patients requiring surgery for spinal metastasis, primarily those over 65, has risen due to improved cancer treatments. Surgical intervention targets acute neurological deficits and instability. Anticoagulants are increasingly used, especially in the elderly, but pose challenges in managing bleeding complications. The study examines the correlation between preoperative anticoagulant/antiplatelet use and bleeding risks in spinal metastasis surgery, which is crucial for optimizing patient outcomes.
METHODS: In a retrospective study at our department from 2010 to 2023, spinal tumor surgery patients were analyzed. Data included demographics, neurological status, surgical procedure, preoperative anticoagulant/antiplatelet use, intra-/postoperative coagulation management, and the incidence of rebleeding. Coagulation management involved blood loss assessment, coagulation factor administration, and fluid balance monitoring post-surgery. Lab parameters were documented at admission, preop, postop, and discharge.
RESULTS: A cohort of 290 patients underwent surgical treatment for spinal metastases, predominantly males (63.8%, n = 185) with a median age of 65 years. Preoperatively, 24.1% (n = 70) were on oral anticoagulants or antiplatelet therapy. Within 30 days, a rebleeding rate of 4.5% (n = 9) occurred, unrelated to preoperative anticoagulation status (p > 0.05). A correlation was found between preoperative neurologic deficits (p = 0.004) and rebleeding risk and the number of levels treated surgically, with fewer levels associated with a higher incidence of postoperative bleeding (p < 0.01).
CONCLUSIONS: Surgical intervention for spinal metastatic cancer appears to be safe regardless of the patient\'s preoperative anticoagulation status. However, it remains imperative to customize preoperative planning and preparation for each patient, emphasizing meticulous risk-benefit analysis and optimizing perioperative care.