Search Results (281)

Background/Objectives: Atrial fibrillation (AF) is the most significant modifying risk factor for the development of cardioembolic stroke, which is associated with worse outcomes and higher intrahospital mortality compared to other types of ischemic stroke. Antithrombotic medications are administered as prophylactic treatment in patients with a risk of stroke. The aim of this study was to determine outcome measures in patients with first-ever ischemic stroke and AF regarding prior antithrombotic therapy. Methods: We collected data on stroke risk factors, CHADS₂ score, and international normalized ratio (INR) value in the context of warfarin therapy, as well as data related to localization, stroke severity, and functional outcome at discharge. Results: A total of 754 subjects with first-ever ischemic stroke and AF were included in this cross-sectional study (122 on warfarin, 210 on acetylsalicylic acid, and 422 without prior antithrombotic therapy). The diagnosis of AF was previously unknown in 31% of the subjects. Stroke risk factors (arterial hypertension, hyperlipidemia, diabetes mellitus, and cardiomyopathy) were significantly lower in the group without prior antithrombotic therapy. The anticoagulant group was significantly younger (p = 0.001). Overall, 45.4% of subjects with a previously known AF event and a high risk of developing stroke received anticoagulant therapy. Participants on warfarin had a significantly better functional outcome than those on antiplatelet therapy or without prior antithrombotic therapy (median mRS 4 vs. 5 vs. 5; p = 0.025) and lower NIHSS scores, although the difference was not statistically significant (median 10 vs. 12 vs. 12; p = 0.09). There was no difference between stroke localization among groups (p = 0.116). Conclusions: Our study showed that, in our cohort, first-ever ischemic stroke due to AF was more common in women. Subjects on prior anticoagulant therapy had more favorable outcomes at discharge. Full article

Background: Venous thromboembolism (VTE) is conventionally treated with anticoagulant therapy. In contrast, the core treatment for peripheral artery disease (PAD) is antiplatelet therapy. VTE and PAD share common risk factors and may occur in the same patient. Nonetheless, there is little evidence of the best antithrombotic regimen to use when the two conditions coexist, especially in terms of the extended prevention of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and VTE recurrences. Methods: We conducted an online survey of members of the Italian Society of Angiology and Vascular Medicine (SIAPAV) to explore current prescribing habits for extended antithrombotic therapy in patients with PAD and unprovoked VTE. The survey included four clinical scenarios with variations in age, gender, bleeding risk, index VTE event, and severity of PAD. In all cases, patients had received anticoagulation for 6 months, and the key question was how to continue treatment beyond 6 months from the index VTE event. Results: A total of 174 clinicians participated to the survey. The most common choice was combining antiplatelet therapy with a direct oral anticoagulant (DOAC) at a low dose. Full-dose DOAC alone or antiplatelet therapy alone were less frequently chosen. Older age and high bleeding risk increased the preference for antiplatelet therapy alone. Conclusions: This survey highlights the marked variability in antithrombotic prescribing patterns among specialists in vascular medicine for patients with unprovoked VTE and concomitant PAD, reflecting the lack of evidence on optimal management in this specific setting. More research is needed to define the safest and most effective treatment strategies for patients with concurrent PAD and VTE. Full article

The elderly population in Japan was 29.3% in 2024, the highest in the world, making medical care for elderly patients an urgent social issue. There are challenges in providing care for elderly patients with head injury, since the buffering effect of the expansion of the subdural space due to brain atrophy masks the neurological symptoms caused by a hematoma, making detection difficult. However, brain damage can be detected with high sensitivity and specificity using blood D-dimer as a biomarker without the need for head computed tomography (CT). Also, about 30% of elderly patients with traumatic brain injury (TBI) are taking antithrombotic drugs, and the effects of these drugs on TBI may include an increase in intracranial hematomas and an increased risk of deterioration. Reversal therapy is used as a countermeasure to prevent hematoma expansion, but this requires the administration of a reversal agent early after injury and before hematoma expansion. In decompression surgery, the use of a mini-craniotomy with neuroendoscopic assistance under local anesthesia can reduce invasiveness, and this method significantly reduces intraoperative bleeding and operation times compared to a major craniotomy. These innovations have improved mortality for TBI in elderly patients, but there is still a need for improvements in functional outcomes. Full article

Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide’s potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection (“long-COVID”), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action. Full article

Background: The optimal antithrombotic therapy after transcatheter aortic valve replacement (TAVR) remains uncertain. Limited data exist comparing novel oral anticoagulants (NOACs) with standard antiplatelet therapy in this population. Methods: We conducted a retrospective analysis of 171 patients who underwent TAVR between January 2018 and August 2024. Patients were categorized according to the discharge antithrombotic regimen as follows: NOACs (n = 27, 16%), vitamin K antagonists (VKAs; n = 8, 5%), and antiplatelet therapy only (APT-only; aspirin and/or clopidogrel without oral anticoagulation; n = 136, 79%). Due to the small VKA sample size, the primary analysis compared NOACs with APT-only. VKA outcomes were reported descriptively without statistical comparisons. Results: Compared with APT-only, NOAC users had significantly higher 30-day mortality (33% vs. 12%, p = 0.017) and 1-year mortality (41% vs. 20%, p = 0.048). NOACs were associated with higher rates of major adverse cardiovascular events (MACCE) at 30 days (22% vs. 8%, p = 0.051) and 1 year (34% vs. 17%, p < 0.001). After inverse probability treatment weighting, NOACs showed increased odds of 30-day MACCE (OR 5.59, 95% CI 2.56–12.18, p < 0.001) and increased hazard of 1-year mortality (HR 2.22, 95% CI 1.22–4.03, p = 0.009). Conclusions: NOAC use was associated with inferior outcomes compared to antiplatelet therapy in post-TAVR patients, although residual confounding cannot be excluded. Given the limited sample size and retrospective design, these hypothesis-generating findings require validation in larger prospective studies before they can influence clinical practice. Full article

Background/Objectives: Despite progress in secondary prevention, people with chronic coronary syndrome (CCS) still face a residual risk of ischemic events. Antithrombotic therapy reduces this risk and helps stabilize chronic cardiovascular disease. Studies have shown that combining low-dose rivaroxaban with aspirin—an approach called dual-pathway inhibition (DPI)—can lower this risk and reduce major adverse cardiovascular events (MACEs). However, researchers have not yet gathered enough real-world data to confirm the efficacy and safety of this strategy. The DUTCH CCS registry aims to collect real-world data on how effective and safe low-dose rivaroxaban combined with aspirin is for patients with CCS in The Netherlands. The study aims to provide insights into the outcomes, benefits, and risks of DPI in a real-world setting, beyond the scope of controlled clinical trials. Methods: The DUTCH CCS registry operates as a national, multicenter, prospective observational study. It enrolls 1000 patients with CCS who receive rivaroxaban (2.5 mg twice daily) and aspirin (80 mg or 100 mg once daily). The study targets individuals at high ischemic risk due to coronary artery disease (CAD) and follows a single-arm design. Researchers will measure the primary efficacy endpoint by tracking MACEs, clinically driven coronary, peripheral, or carotid revascularization, and stent thrombosis over one year. They will assess the primary safety endpoint by recording major bleeding events at one year. The team will collect data at both 3-month and 1-year follow-ups. Conclusions: As an observational study, this registry is not designed to establish causality. However, it seeks to improve our understanding of how DPI performs in real-world secondary prevention for CCS patients. The results may help update treatment guidelines and inform clinical decisions in everyday practice. Full article

The current management of patients with acute coronary syndrome (ACS) and bleeding disorders, such as hemophilia, is supported by small retrospective studies or expert consensus documents. Moreover, people with hemophilia are less likely to receive invasive treatments like percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for ACS compared to those without hemophilia, which could affect their cardiovascular outcomes. A multidisciplinary team with an expert hematologist is essential to properly define the therapeutic strategy, which should balance both the thrombotic and bleeding risks. We report a clinical case that illustrates an alternative revascularization strategy for hemophilic patients presenting with ACS and with a pattern of diffuse coronary atherosclerotic disease (CAD), encompassing drug-coated balloons (DCBs) in combination with spot stenting. The proposed approach might avoid a full-length drug-eluting stent (DES) implantation and also allow a short dual antiplatelet therapy (DAPT) regimen that is desirable in patients at a very high bleeding risk (HBR) like hemophiliacs. Furthermore, we have provided a review of the available literature on this topic and a focus on the main recommendations for managing ACS, in response to the presented clinical case. Finally, this article aims to share information and develop more confidence in the current guidelines on the treatment of hemophiliacs who need myocardial revascularization. Full article

Background/Objectives: Large clinical trials have established the optimal antiplatelet strategy in the wide spectrum of coronary artery disease. However, data are scarce regarding MINOCA and the aim of our study is to present data from the current clinical practice. Methods: A total of 151 patients were included in this study after exclusion of 27 patients with myocarditis and other diagnoses. A cardiac magnetic resonance (CMR) performed at 123/151 patients demonstrated an ischemic pattern of late gadolinium enhancement (LGE) confirming the diagnosis of true acute myocardial infarction (AMI) in 42 cases (28%). Based on multimodality imaging and clinical judgement, Takotsubo syndrome (TTS) was diagnosed in 55 patients (36%), whereas CMR failed to reveal abnormal findings in 54 cases (36%), categorized as MINOCA of unknown origin. Results: Regarding antithrombotic prescriptions at discharge, 38% of patients received dual antiplatelet (DAPT) or dual antithrombotic therapy (DAT, 1 antiplatelet plus 1 anticoagulant), 49.7% received single antiplatelet (SAPT) or anticoagulant, and 12% received no antithrombotic treatment. Univariate analysis showed that the likelihood of prescribing DAPT or DAT was associated with left ventricular ejection fraction (LVEF) (r = 0.202, p = 0.013), atherosclerotic lesions on coronary angiography (r = 0.303, p < 0.001), prior use of anticoagulants (r = −0.258, p = 0.001), and marginally with the INTERTAK score (r = −0.198, p = 0.044). A multivariable model, adjusted for age, LVEF, ECG abnormalities, and history of anticoagulant use, confirmed the independent association between angiographic evidence of atherosclerosis and the decision for DAPT/DAT (OR: 0.334, 95% CI: 0.307–0.813, p < 0.001). However, the initial treatment decision did not seem to impact 2-year prognosis in our population. Conclusions: Our study results reveal that decision making in the antithrombotic strategy for MINOCA patients poses a challenge in clinical practice. More robust data are required for definite conclusions on the prognostic implications. Full article

Cardiovascular disease is the primary cause of mortality and morbidity in patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD) undergoing hemodialysis. This paper examines the challenges of managing acute coronary syndrome (ACS) in ESRD patients, focusing on the delicate balance between thrombotic and bleeding risks. The review explores the mechanisms underlying the increased thrombotic risk in ESRD, including elevated platelet aggregation, endothelial dysfunction, and alterations in coagulation factors. Paradoxically, ESRD patients also exhibit higher bleeding tendencies due to platelet dysfunction and other uremia-related factors. The efficacy and safety of various antiplatelet therapies, including aspirin and P2Y12 inhibitors, are evaluated in this population. While potent P2Y12 inhibitors such as ticagrelor and prasugrel have demonstrated potential in reducing ischemic events, they are associated with an increased bleeding risk. The optimal duration of anti-platelet therapy (DAPT) in ESRD patients remains controversial, with studies suggesting potential benefits of prolonged DAPT but also increased bleeding risk. This review underscores the necessity for further research and patient inclusion in clinical trials to establish evidence-based guidelines for tailoring antithrombotic therapy in this high-risk population. Full article

The optimal long-term antithrombotic treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains controversial. Current guidelines recommend a short initial period of triple antithrombotic therapy (e.g., 1 week), followed by dual therapy consisting of an oral anticoagulation agent and a single antiplatelet agent for 6 months in patients undergoing elective PCI and 12 months in patients with acute coronary syndromes. After this course of combination therapy, anticoagulation monotherapy is recommended. In daily practice, however, the optimal strategy for long-term antithrombotic therapy remains debated. A growing body of evidence supports the safety and efficacy of oral anticoagulation monotherapy, but its use in clinical practice remains inconsistent. This review aims to evaluate the available evidence on chronic antithrombotic regimens in patients with AF undergoing PCI, with a focus on key clinical considerations, such as the selection of optimal long-term therapy that balances ischemic and bleeding risks. It also highlights that, despite robust supporting evidence, significant gaps persist in real-world implementation. Full article

Interleukin-6 (IL-6) is a pleiotropic cytokine with critical roles in immune regulation, inflammation, and haematopoiesis. While its functions in host defence and tissue repair are well established, accumulating evidence suggests that IL-6 also can directly and indirectly modulate megakaryocyte and platelet biology. This review examines the mechanistic basis supporting IL-6-mediated platelet hyper-responsiveness, in addition to its effect on megakaryopoiesis and thrombopoiesis in thromboinflammatory disease states. We discuss how IL-6-mediated trans-signalling may sensitizes platelets to activation, and that this may be exclusive to glycoprotein VI (GPVI) stimulation due to Janus kinase (JAK)–signal transducer 2 crosstalk, in addition to other mechanisms that may contribute to priming platelets. We further highlight clinical evidence linking IL-6 to thrombotic complications in cardiovascular disease and infection (e.g., COVID-19 and sepsis). Given the emerging interest in IL-6-targeting therapies as anti-inflammatory and anti-thrombotic agents, a thorough understanding of how IL-6 can drive platelet responsiveness is crucial. Full article

Bleeding complications are a significant concern in the management of acute coronary syndromes (ACS). The evidence from clinical trials demonstrates the need for balancing efficacy in reducing ischemic events with safety concerns, as bleeding events adversely affect prognosis and mortality. Pharmacological agents like aspirin, P2Y12 inhibitors (e.g., prasugrel, ticagrelor), glycoprotein IIb/IIIa inhibitors, and heparins are fundamental to ACS treatment but carry varying bleeding risks depending on individual patient profile. Recent advancements in risk stratification tools have enabled tailored approaches to dual antiplatelet therapy (DAPT), optimizing its duration based on bleeding and thrombotic risks. Further Emerging therapies, including shortened DAPT protocols and P2Y12 inhibitor monotherapy, have shown promise in minimizing bleeding while maintaining clinical efficacy. The findings underscore the importance of personalized antithrombotic regimens in ACS management, emphasizing precise risk assessment to enhance outcomes and mitigate adverse events. This review examines the mechanisms, risk factors, and strategies to mitigate bleeding associated with anticoagulant and antiplatelet therapies in ACS. Full article

Current αIIbβ3 antagonists are potent antithrombotic agents, their clinical use is limited by the risk of life-threatening bleeding. Emerging evidence has highlighted key mechanistic differences between thrombosis and hemostasis, opening avenues for safer antithrombotic strategies. Targeting integrin αIIbβ3 outside-in signaling has been proposed to mitigate bleeding risk; however, the short half-life of peptide-based therapeutics remains a major challenge. In this study, we developed an optimized αIIbβ3 antagonist, KGDRR—a recombinant mutant protein derived from snake venom disintegrin, incorporating an Arg55 residue within the KGD loop—through systematic structure–activity relationship (SAR) analysis. Molecular docking revealed a critical cation–π interaction between Arg55 of KGDRR and Tyr122 of the β3 subunit, stabilizing integrin αIIbβ3 in an unliganded-closed conformation. Functionally, KGDRR selectively inhibited thrombus propagation by blocking ligand binding and downstream Gα13-mediated outside-in signaling while preserving initial thrombus core formation, which is a limitation of current αIIbβ3 inhibitors. Unlike conventional antagonists, KGDRR maintained αIIbβ3 in an unliganded-closed conformation without inducing the integrin activation and conformational change that lead to immune-mediated platelet clearance and thrombocytopenia. In animal models, KGDRR effectively suppressed thrombus growth without causing thrombocytopenia or prolonging bleeding time. Furthermore, intramuscular administration of KGDRR achieved a functional half-life 3.5 times longer than that of the clinically used antithrombotic eptifibatide at equivalent antithrombotic efficacy. In conclusion, KGDRR exhibits potent antithrombotic activity with a favorable safety profile and enhanced pharmacokinetic stability. These findings position KGDRR as a promising next generation αIIbβ3 antagonist with the potential to improve clinical outcomes in antithrombotic therapy. Full article

Multisystem inflammatory syndrome in children (MIS-C) is a rare, delayed hyperinflammatory response, which occurs 2–6 weeks after SARS-CoV-2 infection. Main symptoms include fever, involvement of at least two organ systems, elevated inflammatory markers and evidence of infection with or exposure to SARS-CoV-2. While the prognosis is generally favorable, complications—such as myocardial dysfunction, coronary aneurysms, and coagulation disorders—can lead to severe outcomes, including death. Immunomodulatory and antithrombotic therapies are key components of treatment. We report a clinical case of a 3-year-old boy who developed MIS-C, initially presenting with fever, multiorgan involvement, and confirmed SARS-CoV-2 infection, along with a coinfection caused by group A β-hemolytic Streptococcus (GAS) isolated from throat culture. On the ninth day of illness, thrombosis of the right subclavian vein was detected. Subsequent genetic testing for thrombophilia revealed that the patient was a heterozygous carrier of Factor V Leiden, Factor V HR2, and PAI-1 4G/5G polymorphisms. Thromboembolic events (TEs) are serious and potentially life-threatening complications of MIS-C. This case highlights the occurrence of TE in a 3-year-old boy, an age group younger than typically observed, emphasizing the need for heightened awareness, early detection, and prompt intervention. Additionally, it underscores the importance of careful monitoring of thrombotic risks in MIS-C patients, particularly those with underlying prothrombotic conditions, to prevent severe outcomes. Full article

Scolopendra subspinipes, commonly known as the Chinese red-headed centipede, has been utilized in traditional East Asian medicine for centuries to treat conditions such as chronic pain, inflammation, convulsions, and infections. Recent pharmacological investigations have uncovered a wide array of bioactive molecules—including peptides, alkaloids, and polysaccharide–protein complexes—from both venom and whole-body extracts. This review synthesizes findings from 45 in vitro, in vivo, and clinical studies investigating the pharmacological effects of venom-derived and whole-body-derived compounds from S. subspinipes across multiple domains, including analgesic, anti-inflammatory, antimicrobial, antifungal, antioxidant, antitumor, antithrombotic, anti-fibrotic, and neuroprotective activities, along with a brief scoping review of clinical practice guidelines. Key venom-derived compounds such as the peptide SsmTX-I, immunomodulatory antimicrobial peptide scolopendrasin IX, and antitumor peptide scolopentide exhibit strong mechanistic rationale and preclinical efficacy, positioning them as lead candidates for clinical development. Compounds derived from whole-body extracts, including alkaloids and polysaccharide–protein complexes, also demonstrate promising therapeutic potential. Mechanistic studies suggest these compounds operate via distinct pathways—such as ion-channel inhibition, NF-κB suppression, and apoptosis induction—offering potential advantages over existing therapies. However, current evidence remains primarily preclinical, and challenges such as extract variability, immunogenicity, and lack of standardized dosing must be addressed. Future research should prioritize isolation and structural optimization of key peptides, standardized formulation development, toxicological profiling, and early-phase human trials. The integration of traditional knowledge and modern pharmacological insights underscores the potential of venom- and whole-body-derived S. subspinipes agents to enrich the drug discovery, particularly for conditions with unmet therapeutic needs. Full article