Search Results (365)

Background: Bleeding is the most important complication of percutaneous liver biopsy. However, there are many unknowns regarding the management of antithrombotic agents in percutaneous liver biopsy. We investigated whether percutaneous liver biopsy could be performed safely by withdrawal of antithrombotic agents in accordance with the criteria of gastroenterological endoscopy guidelines. Methods: A retrospective study was conducted on patients who underwent percutaneous liver biopsy. Antithrombotic agents were discontinued in accordance with the withdrawal criteria in the Japan Gastroenterological Endoscopy Society guidelines for gastroenterological endoscopy. Results: A total of 630 cases were enrolled, including 64 cases receiving antithrombotic therapy. Bleeding complications occurred in 6.7% of cases with antithrombotic therapy and 2.1% of patients without antithrombotic therapy, with no significant difference between the two groups (p = 0.069). Major bleeding requiring surgical intervention or transarterial embolization was not observed in cases with antithrombotic therapy. Only one case (1.6%) developed thromboembolism after withdrawal of antithrombotic agents. Even after propensity score matching, there was no significant difference in the bleeding complication rates between the cases with and without antithrombotic therapy in either tumor biopsy (p = 0.599) and non-tumor biopsy (p = 0.440). Univariate and multivariate analysis revealed that low platelet count (≤10 × 10⁴/μL) was a significant risk factor for bleeding complications (OR = 1.07, 95%CI 1.01–1.15, p = 0.034), whereas antithrombotic therapy was not a significant factor (OR = 2.7, 95%CI 0.79–9.22, p = 0.114). Conclusions: This study suggests that percutaneous liver biopsy may be performed safely in cases receiving antithrombotic therapy by discontinuation of antithrombotic agents in accordance with the withdrawal criteria of Japan Gastroenterological Endoscopy Society guidelines for gastroenterological endoscopy. Full article

Aspirin has been the default backbone of antiplatelet therapy after percutaneous coronary intervention (PCI) for over two decades, anchored by landmark trials that established 12-month dual antiplatelet therapy (DAPT) as the standard of care. Three developments have prompted reassessment of this paradigm: the markedly lower thrombotic risk of contemporary drug-eluting stents, the greater potency and consistency of potent P2Y₁₂ inhibitors (ticagrelor, prasugrel), and increasing recognition that major bleeding independently worsens outcomes after PCI. Recent randomised trials have systematically tested aspirin withdrawal at varying time points. Immediate aspirin-free strategies (NEO-MINDSET, STOPDAPT-3) demonstrated an early signal of excess ischaemic events in the ACS component of enrolled populations, suggesting that aspirin remains important during the earliest post-PCI period in ACS. One-month strategies (T-PASS, ULTIMATE-DAPT, TARGET-FIRST) and three-month strategies (TWILIGHT, TICO, DUAL-ACS) showed that transition to P2Y₁₂ monotherapy after an initial DAPT period significantly reduces bleeding without increasing ischaemic events in selected populations. Beyond one year, long-term randomised trials including the HOST-EXAM 10-year follow-up (Lancet 2026) and the STOPDAPT-2 5-year landmark analysis (Circ Cardiovasc Interv 2026), together with study-level meta-analyses (PANTHER) and recent individual patient data meta-analyses, provide converging evidence that clopidogrel monotherapy outperforms aspirin for chronic secondary prevention without excess bleeding. The choice of P2Y₁₂ agent is critical: clopidogrel monotherapy in ACS during the first post-procedural year carries excess thrombotic risk owing to CYP2C19 pharmacogenomic variability, whereas ticagrelor and prasugrel provide more reliable protection. This review synthesises the mechanistic rationale, trial evidence across all time points, special clinical contexts (oral anticoagulation, coronary artery bypass grafting, high bleeding risk), guideline evolution, and methodological considerations, providing a practical framework for individualising post-PCI antiplatelet therapy. Full article

Cerebral venous thrombosis (CVT) is a rare but potentially life-threatening subtype of stroke, characterized by thrombus formation within the dural venous sinuses and cerebral veins. Recent advances have deepened our understanding of CVT pathophysiology, highlighting a multifactorial process that encompasses thrombus initiation, subsequent thrombus propagation, venous hypertension with blood–brain barrier disruption, and secondary parenchymal brain injury. Comprehensive clinical assessment, including diagnosis and differential diagnosis, disease severity scores, imaging-based metrics, and prognostic scoring systems, enables accurate evaluation and risk stratification. Emerging therapeutic strategies, including direct oral anticoagulants, corticosteroids for selected patients, natural-origin agents, immunomodulatory therapy, endovascular treatment, optic nerve sheath fenestration, and neuromodulation, provide novel and alternative options for the management of CVT. This review provides a comprehensive overview of CVT pathophysiology, clinical assessment tools, and novel therapeutic strategies to guide clinical decision-making and inform future research. Full article

Background/Objectives: Atrial fibrillation (AF) is highly prevalent among older adults and is associated with increased thromboembolic risk. Although anticoagulant therapy (AC) is strongly recommended, its use in elderly and multimorbid patients remains suboptimal. This study aimed to describe long-term trends in AC prescribing patterns among hospitalized older patients with AF. Methods: We conducted a retrospective observational analysis using data from the Italian REPOSI registry, including patients aged ≥65 years hospitalized with AF between 2010 and 2023. AC at admission and discharge was analyzed, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and antiplatelet agents. Temporal trends, admission-to-discharge treatment changes, and patient characteristics associated with therapy modification were assessed descriptively. Results: The study included 2061 AF patients, characterized by multimorbidity and high thromboembolic risk. A marked shift from VKAs to DOACs was observed over time. However, a substantial proportion of cases remained without AC or received only antiplatelet therapy at both admission and discharge, with untreated individuals being generally older and more clinically complex. DOAC use increased steadily but showed a slight decline at discharge after 2020. Clinical variables available in the registry only partially explained AC changes during hospitalization. Conclusions: Despite increasing adoption of DOACs, AC underuse remains frequent among elderly hospitalized patients with AF. These real-world data highlight persistent challenges in AC management in complex older adults and underscore the need for more comprehensive clinical information and data-driven tools to support individualized therapeutic decision-making. Full article

Background: The clinical outcomes of patients with intracranial haemorrhage (ICH) whilst using direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) are uncertain. This study aimed to assess outcomes and management in patients receiving DOACs compared with those receiving VKAs. Methods: In this retrospective study, patients hospitalised during the period from 1 January 2017 to 31 December 2023 for traumatic and non-traumatic ICH and using oral anticoagulants (OACs) were included. The primary outcomes were mortality and functional outcomes, as measured by the modified Rankin Scale (mRS) during admission and 90-day follow-up. ICH management and complications were studied and compared between the two OAC groups. Results: A total of 171 eligible patients were included, comprising 24 patients on DOACs and 147 patients on VKAs. Patients receiving DOACs were older (79.1 vs. 66.8, p < 0.001) and had a higher proportion of traumatic ICH (75.0% vs. 46.3%, p = 0.009) than those receiving VKAs. In-hospital and 90-day outcomes were not statistically different between the two groups, with an adjusted odds ratio (aOR) of 1.30 (0.39–4.36) for in-hospital mortality, p = 0.67, and an aOR of 0.89 (0.33–2.41) for mRS 0–2 at 90 days, p = 0.83. In total, 81.3% of patients received at least one reversal agent; fresh frozen plasma was commonly used in the VKA group (78.9% vs. 33.3%, p < 0.001), whereas prothrombin complex concentrate was significantly prescribed in patients with DOAC-associated ICH (29.2% vs. 3.4%, p < 0.001). Conclusions: Patients with DOAC-associated ICH had comparable in-hospital and long-term clinical outcomes to those with VKA use. Full article

Patient Blood Management (PBM) has evolved from a transfusion-centered practice to a structured, patient-focused perioperative strategy aimed at improving surgical outcomes while preserving blood resources. In the operating room, where bleeding risk is anticipated and modifiable, PBM requires proactive intervention rather than reactive transfusion. This review synthesizes current evidence on perioperative blood conservation strategies specifically relevant to surgeons and anesthesiologists. Preoperative optimization begins with systematic identification and correction of anemia, most commonly iron deficiency, using appropriately timed oral or intravenous iron therapy and, in selected cases, erythropoiesis-stimulating agents. Careful management of anticoagulant and antiplatelet therapies, early recognition of acquired or inherited coagulopathies, and protocol-driven reversal strategies further reduce perioperative hemorrhagic risk. Intraoperatively, blood conservation depends on meticulous surgical technique, respect for anatomical planes, minimally invasive approaches, and the judicious use of advanced energy devices and topical hemostatic agents. Pharmacologic interventions—particularly tranexamic acid administered with appropriate timing and dosing—have demonstrated consistent reductions in blood loss and transfusion requirements across multiple surgical disciplines. Goal-directed coagulation management guided by viscoelastic testing allows targeted correction of specific hemostatic deficits while minimizing unnecessary blood product exposure. Acute normovolemic hemodilution and intraoperative cell salvage provide additional benefit in selected high-blood-loss procedures. Collectively, these multimodal strategies shift perioperative care from product-driven transfusion toward physiology-based blood conservation. When embedded within institutional protocols and supported by multidisciplinary collaboration, perioperative PBM reduces transfusion exposure, decreases morbidity, shortens hospital stay, and promotes sustainable stewardship of blood resources without compromising patient safety. Full article

Thromboembolic disorders remain a primary cause of mortality globally, with their burden expected to increase due to an aging population. While various antithrombotic agents exist, many patients still rely on traditional gold-standard drugs like heparin, warfarin, and aspirin, which present significant drawbacks. These include the need for injections, frequent monitoring, dietary restrictions, drug interactions, bleeding complications, or other adverse reactions such as thrombocytopenia. In contrast, direct oral anticoagulants offer advantages over warfarin, including fewer interactions and less need for continuous monitoring. However, even with newer drugs, patients face risks of major bleeding events. Current research focuses on novel antithrombotic agents with superior efficacy and enhanced safety compared to existing treatments. Researchers are exploring specific clinical niches, such as factor XI/XII inhibitors for cancer patients, to facilitate evaluation against standard treatments. The development of new antiplatelet drugs, like subcutaneous zalunfiban and selatogrel for pre-hospital therapy of myocardial infarction, and specific reversal agents, such as bentracimab for ticagrelor, exemplify this trend. Future research will likely focus on addressing the unmet needs of specific patient groups. This narrative review aimed to describe the current antithrombotic treatment and the most promising advances in the pharmacological management of thrombosis. Full article

Background: Direct oral anticoagulants (DOACs) have transformed antithrombotic therapy but carry significant bleeding risks requiring prompt reversal. Recent regulatory changes have altered the reversal landscape, notably with the withdrawal of andexanet alfa from the U.S. market. Anticoagulation stewardship programs (ASPs) are essential for navigating this evolving environment and optimizing safe use of anticoagulants. Methods: This narrative review synthesizes evidence from landmark clinical trials (RE-VERSE AD, ANNEXA-4, ANNEXA-I), contemporary guidelines, emerging literature on reversal agents, and critical regulatory updates including the 2025 U.S Food and Drug Administration (FDA) withdrawal of andexanet alfa. Results: Idarucizumab remains the only FDA-approved specific antidote for dabigatran. Following the withdrawal of andexanet alfa, prothrombin complex concentrates (PCCs), both 4-factor and activated are now the primary reversal options for Factor Xa inhibitors, with recent evidence demonstrating comparable hemostatic efficacy. Ciraparantag, a universal reversal agent, is currently in Phase III development. Effective ASPs must now adapt protocols to the post-andexanet era while ensuring timely access to alternative reversal strategies. Conclusions: The reversal landscape has undergone a fundamental transformation with the loss of andexanet alfa. Success in DOAC-associated bleeding management now depends on optimizing PCC-based strategies, integrating systematic stewardship approaches, and preparing for emerging universal antidotes. Institutions must urgently update algorithms, ensure PCC availability, and monitor outcomes in this new therapeutic environment. Full article

Background: Unfractionated heparin (UFH) remains the standard anticoagulant for extracorporeal membrane oxygenation (ECMO), despite complications, such as heparin resistance, heparin-induced thrombocytopenia, bleeding and variable pharmacokinetics. This has prompted the search for alternative and novel anticoagulation strategies, including pharmacologic agents, circuit modifications, and monitoring approaches. This scoping review aimed to map the breadth and characteristics of evidence on ECMO anticoagulation strategies beyond UFH. Methods: A comprehensive search of peer-reviewed and gray literature was conducted across PubMed, Cochrane, Clinical Trials, WHO Trials Registry, and conference abstracts through manual searches in key journals. Clinical, pre-clinical, and gray literature studies evaluating pharmacologic agents, anticoagulation-free or heparin-sparing, biocompatible circuits, and monitoring innovations were included. Data were charted and synthesized descriptively to identify trends, gaps, and emerging directions. Results: A total of 269 records were included. Evidence was highly heterogeneous among study designs, populations, ECMO modalities, and outcome definitions. Most clinical studies were retrospective cohorts and adult-centered, with limited multicenter randomized controlled trials and underrepresentation of neonatal and pediatric populations. Direct thrombin inhibitors were frequently studied and clinically implemented alternatives to UFH. Other agents, including nafamostat mesylate, prostaglandin E1, and factor pathway inhibitors remain early in clinical investigation. Anticoagulation-free strategies and biocompatible circuit technologies were mostly supported through pre-clinical and single-center studies. Monitoring and modeling innovations, like TEG, ROTEM, real-time imaging, and machine learning, are quickly emerging. Conclusions: ECMO anticoagulation is transitioning from UFH reliance toward diversified and personalized strategies. Future research should prioritize multicenter randomized controlled trials, standardize protocols, expand to neonatal and pediatric investigation, and integrate strategies. Full article

Platelet-rich plasma (PRP) is widely used in orthopedics and sports medicine as an autologous product; however, substantial heterogeneity in manufacture and incomplete reporting of preparation parameters limits reproducibility and inter-study comparability.: We performed a PRISMA-guided methodological review of studies describing PRP preparation, subsequently focusing on orthopedic applications. MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, Web of Science, and Google Scholar were searched. 7330 records were retrieved; following merging and de-duplication, more than 2500 unique records were screened. The inclusion criteria for our study required studies on PRP that focused on orthopedic use of this preparation and studies that reported a defined methodology for PRP, reported in the abstract or in the manuscript. Extracted variables covered collection and anticoagulation, centrifugation strategy, cellular composition, activation/lysis, processing environment, storage, and time-to-use. Twenty-three orthopedic studies met the inclusion criteria. Whole blood draw volume and anticoagulant were reported in 15/23 studies each; centrifugation parameters (relative centrifugal force/RPM and duration) in 12/23; and PRP phenotype (e.g., leukocyte-poor vs. leukocyte-rich) in 15/23. Platelet metrics (baseline and/or final platelet count/concentration) were reported in 6/23. Sterility/environmental controls were mentioned in 17/23, whereas storage conditions and time-to-use were described in only 3/23. An explicit exogenous activation agent was reported on 1/23. Orthopedic PRP studies frequently omit critical manufacturing and handling descriptors—particularly platelet dose, leukocyte/lymphocyte handling, temperature control, storage/freezing conditions, and time-to-administration—impairing reproducibility and dose comparability. We propose a pragmatic, standardized protocol for preparation of leucocyte/lymphocyte-depleted PRP for orthopedic use (PRP only, without gelification), together with a minimum set of data and parameters to be evaluated. In our opinion these parameters should be included in future studies in order to standardize the production process. The quality of PRP itself could be impacted by such standardization, and the ability to objectively evaluate the results of studies could be enhanced by facilitating the comparison of data emerging from the literature. Full article

Background: There is growing interest in plant-derived compounds for managing vascular diseases. Veratramine (VRT), a steroidal alkaloid isolated from plants of the Veratrum genus, exhibits diverse biological effects such as antihypertensive, analgesic, and antitumor activities, yet its influence on hemostasis and thrombus formation has not been characterized. This investigation sought to determine whether VRT exerts anticoagulant effects using integrated in vitro and murine models. Methods: VRT’s anticoagulant profile was comprehensively evaluated using integrated biochemical, cellular, and murine models, including clotting time assays (aPTT/PT), chromogenic enzymatic assays, fibrin polymerization analysis, platelet aggregometry, and endothelial modulation of PAI-1/t-PA under inflammatory conditions. Results: VRT treatment significantly prolonged both intrinsic and extrinsic coagulation times, directly inhibited enzymatic activities of thrombin and FXa, and attenuated their generation by endothelial cells. Additionally, VRT interfered with fibrin clot formation and diminished agonist-induced platelet aggregation. Ex vivo coagulation analyses confirmed its anticoagulant action, while endothelial studies revealed a reduced PAI-1/t-PA ratio following VRT exposure. Conclusions: These data establish VRT as possessing novel direct dual inhibition of thrombin and FXa alongside suppression of fibrin polymerization, platelet reactivity, and PAI-1 expression—positioning it as a promising multifunctional anticoagulant agent. While preclinical murine models preclude direct clinical translation absent pharmacokinetic data, these findings warrant further mechanistic and translational investigation. Full article

This review presents an innovative and timely exploration of how cytoprotection can serve as a cohesive therapeutic approach by which to address the hemorrhage–thrombosis paradox. Presenting counteraction of both hemorrhage and thrombosis as phase-dependent outcomes of vascular dysregulation, the manuscript synthesizes conceptual, experimental, and clinical evidence into a unified systems-level model focused on the stable gastric pentadecapeptide BPC 157, which acts as a cytoprotective mediator. In rodents, BPC 157 can simultaneously counteract hemorrhage and thrombosis without directly affecting the coagulation cascade (aggregometry, thromboelastometry). This cytoprotective framework (decreased hemorrhage, decreased thrombosis) stands with presentation of both hemorrhage and thrombosis in the wound, arrhythmias, and Virchow triad, and resolution of these disturbances. As proof of the concept (full cytoprotective effect), a vasoprotective cytoprotective mediator capable of bidirectional regulation, BPC 157, is effective for wound healing, arrhythmia control, and normalization of Virchow’s triad (i.e., following major injuries, occlusion/occlusion-like syndromes). As a comparison from a cytoprotective (partial vs. full) standpoint, conventional agents—anticoagulants, antiplatelet drugs, and fibrinolytics—provide only partial protection by targeting isolated components of hemostasis. Beta blockers, calcium channel blockers, prostaglandins, NO modulators, ACE inhibitors, and statins each exert broader cytoprotective effects; however, these actions remain incomplete and context-dependent, typically unidirectional, dose-limited, or are achieved at the expense of opposing pathological risks. Contrarily, for BPC 157, decreased hemorrhage (including both anticoagulants and antiplatelet agents), decreased thrombosis, effective wound healing, arrhythmia control, and normalization of Virchow’s triad involve preservation of endothelial integrity, normalization of microcirculation, modulation of the NO system, stabilization of hemostatic balance, and recruitment of adaptive collateral pathways. Nevertheless, reliance on preclinical models necessitates further clinical validation. Full article

Perioperative management of antithrombotic therapy in oral surgery represents an evolving paradigm. This critical review evaluates the contemporary scientific evidence that challenges the conventional practice of routinely discontinuing anticoagulants and/or antiplatelet agents to prevent postoperative bleeding. The traditional strategy carries an unacceptable risk of iatrogenic, sometimes severe, thromboembolic events. The aim of this systematic narrative review is to synthesize the current evidence (2015–2025) and to outline a new, patient-centered clinical framework that dynamically balances thromboembolic and hemorrhagic risks. Materials and methods: A systematic search of major databases (PubMed/MEDLINE, Scopus, Web of Science) identified relevant studies, structured according to the PICO framework. The search strategy prioritized high-level evidence, including clinical guidelines, systematic reviews, meta-analyses, randomized controlled trials, and prospective cohort studies published between January 2015 and November 2025. Results: The results reinforce an emerging consensus: the basis of safe management is the rigorous application of advanced local hemostasis techniques (e.g., prioritizing resorbable materials, sutures, topical hemostatic agents, and antifibrinolytics) and the use of perioperative decision-making algorithms. These measures allow, in most routine dental surgical procedures, the safe continuation of antithrombotic therapy, thus minimizing the thromboembolic risk without significantly increasing the risk of clinically significant bleeding. In the future, research should focus on optimizing materials science (novel biomaterials and controlled-release systems) and on standardizing and validating protocols in specific populations (e.g., patients on combination therapy or at extreme cardiovascular risk). This review argues that the adoption of this evidence-based model, with local hemostasis as a critical pillar, is essential for modern, ethical, and safe dental practice. Full article

Background/Objectives: Traumatic brain injury in elderly patients is a significant public health concern, particularly for those on antithrombotic therapy. A clearer understanding of how different antithrombotic agents affect the likelihood of intracranial hemorrhage in elderly patients with TBI is needed to guide clinical management. Therefore, the objective of this study was to assess the effect of preinjury antithrombotic agents on the incidence of intracranial hemorrhage in elderly patients with traumatic brain injury. Methods: The design was a retrospective cohort study set in a regional Australian hospital emergency department. The study evaluated elderly patients (≥65 years) with head injury cases identified from the integrated electronic medical record using SNOMED codes. Data on patient demographics, antithrombotic use, computed tomography imaging, and outcomes were collected. Results: A total of 152 elderly TBI patients were included in the study. Of these patients, 90.1% had falls leading to TBI. Among the patients, 30.3% were on antiplatelet agents, 23% were on direct oral anticoagulants, 7.2% were on vitamin K antagonists, and 39.5% were not on any antithrombotic agents. Intracranial hemorrhage was found in 26.5% of patients, with both direct oral anticoagulants (aOR 4.87, 95% CI 1.42–16.67, p < 0.01) and vitamin K antagonists (aOR 4.95, 95% CI 1.04–23.55, p < 0.04) demonstrating statistically significant associations with increased odds of ICH. Conclusions: Both vitamin K antagonists and direct oral anticoagulants were associated with a higher odds of intracranial hemorrhage in elderly patients with TBI, while antiplatelet therapy did not show this effect. Full article

The bioactive compounds that are produced by leeches combine traditional and modern treatment since the saliva of the animal contains proteins and peptides with anticoagulant, anti-inflammatory, antimicrobial, antioxidant, and regenerative properties. In this review, their biochemical profile, mechanisms and clinical uses are considered with a special focus on the fact that they are utilized to combine traditional practices with the modern developments in biomedical approaches. Proteomic and transcriptomic research has recently found more than 100 bioactive molecules, such as hirudin, calin, eglins, bdellins and destabilase, which are related to the blood-feeding process and therapeutic processes. These compounds control blood clotting, control inflammatory mediators, block microbes and enhance wound healing and the development of new blood vessels. In clinical practice, leech therapy is common in the reconstruction and microsurgical practice to reduce venous congestion and enhance graft success. They are also shown to be useful in wound healing, cardiovascular health, musculoskeletal conditions and regenerative medicine, as well as emerging drug delivery systems of recombinant proteins and nanocarriers. Some of the challenges involve biological variation, infection or bleeding risks and stringent regulations on purity and standardization. Biotechnology has improved through other developments such as recombinant protein production, high-throughput omics, and nanotechnology, which will help resolve these problems, making them safe and scalable for clinical use. Altogether, leech bioactives are the prime examples of the sophisticated pharmacology of nature, which have the potential of being used as therapeutic agents in the future. The recent approach and incorporation in personalized medicine and bioengineering models reflect the leech’s capacity to address complicated illness and unmet healthcare requirements to reassert its significance in preventive medicine and recent biomedicine. Full article