Search Results (365)

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: Thrombosis in light chain amyloidosis (LCA) occurs in the context of multiple organ dysfunction and inflammation. Conventional coagulation tests (screening) may not sufficiently capture the procoagulant substrate in the inflammatory/therapeutic dynamics. Methods: A total of 61 consecutive patients with LCA were prospectively included in the study. Clinical data, including organ involvement, time of diagnosis, treatment phase, DOAC exposure and thrombosis history were systematically recorded and subjected to screening. Specialized hemostasis tests such as APTT/PT, fibrinogen, D-dimer, TEG and TGT were performed and conventional times were analyzed in the subgroup without DOAC. Results: The prevalence of documented thrombosis was 32.8%, and thrombosis status was associated with TEG positivity and more strongly with TGT positivity. Hypercoagulability was identified in 50.8% by TEG and 41.0% by TGT, regardless of whether APTT/PT were within the reference values. APTT/PT did not predict thrombosis recurrence (p > 0.05), which was predicted by TEG (p = 0.0027) and TGT (p = 0.0006). An inflammation/fibrin turnover panel (CRP, fibrinogen, D-dimer) predicted TEG positivity (p < 0.0001), but not TGT, and was correlated with assessment at diagnosis, daratumumab-based therapy, and cardiac involvement. Conclusions: Global tests (TEG/TGT) promptly correlate with thrombosis recurrence in our cohort and provide crucial information in addition to clotting times for thrombotic phenotyping. Inflammation can influence TEG, so the decision to recommend the tests and the timing of their performance should be adapted to the clinical, biological, and therapeutic context. Full article

Patients with atrial fibrillation (AF) who are not candidates for long-term anticoagulation present a complex therapeutic dilemma due to competing risks of cardioembolic stroke and intracerebral hemorrhage (ICH). This challenge is particularly pronounced in neurologically vulnerable individuals, including those with prior ICH, cerebral amyloid angiopathy (CAA), or neuroimaging markers of cerebral small vessel disease (SVD). Left atrial appendage occlusion (LAAO) has emerged as an alternative stroke prevention strategy for patients with contraindications to anticoagulation; however, optimal patient selection and post-procedural antithrombotic management remain uncertain, largely because existing bleeding risk scores inadequately capture ICH risk. Most hemorrhagic risk scores were designed to estimate systemic bleeding and demonstrate limited ability to predict ICH, as they do not incorporate hemorrhage etiology or neuroimaging features. Importantly, ICH recurrence risk varies substantially by subtype, with the highest risk observed in CAA-related hemorrhage, the lowest in hypertensive SVD, and intermediate risk in mixed or secondary etiologies. These distinctions have direct implications for anticoagulation decisions and consideration of LAAO. Finally, we synthesize contemporary evidence on ICH risk stratification, neuroimaging biomarkers, and antithrombotic strategies following LAAO. We propose a multidisciplinary, evidence-based decision-making framework integrating clinical risk scores, neuroimaging findings, and hemorrhage phenotype to support individualized stroke prevention strategies in high-risk patients with AF. Full article

Background: Thrombocytopenia is traditionally perceived as a bleeding-predominant condition; however, growing evidence indicates that many thrombocytopenic states are paradoxically associated with an increased risk of venous and arterial thrombosis. This dual hemostatic derangement poses major therapeutic challenges when anticoagulant or antiplatelet therapy is indicated, particularly in complex settings such as cancer-associated thrombosis, immune thrombocytopenia, and advanced liver disease. Methods: We conducted a narrative review of the literature published between January 2021 and May 2025 using PubMed and guideline repositories. Search terms included thrombocytopenia, anticoagulation, antiplatelet therapy, cancer-associated thrombosis, immune thrombocytopenia, and cirrhosis. International guidelines from ASH, ISTH, ASCO, EHA, ESC, and AHA were prioritized. Evidence was synthesized to define platelet-based safety thresholds and disease-specific management strategies. Results/Discussion: Thrombocytopenia does not uniformly confer protection against thrombosis. Platelet activation, endothelial dysfunction, inflammatory signaling, impaired fibrinolysis, and procoagulant microparticles contribute to a prothrombotic milieu despite reduced platelet counts. Most guidelines support full-dose anticoagulation at platelet counts ≥ 50 × 10⁹/L, with dose modification between 25 and 50 × 10⁹/L and treatment interruption below 25 × 10⁹/L, depending on thrombotic risk. Antiplatelet therapy requires stricter individualization, particularly regarding dual antiplatelet therapy. Conclusions: Management of antithrombotic therapy in thrombocytopenic patients requires a dynamic, individualized approach balancing ischemic and bleeding risks. Pragmatic algorithms may guide clinical decision-making while prospective data remain limited. Full article

Objectives: To examine the prescribing of non-vitamin K-dependent oral anticoagulants (DOACs) among multidose drug dispensing (MDD) users aged ≥65 years, and to describe associated drug–drug interactions (DDIs), concomitant use of fall-risk increasing drugs (FRIDs) and anticholinergic drugs (AC). Methods: Cross-sectional analysis of anonymized MDD medication lists from 87,519 patients in 2018. DDIs were identified using The Norwegian Medical Products Agency interaction tool, FRIDs were defined using the Swedish National Board of Health and Welfare list, and the CRIDECO Anticholinergic Load Scale assessed anticholinergic burden. Results: Among the 13,215 patients aged 65 and older the mean number of prescribed medications was 10.3. At least one DDI involving the prescribed DOACs was present in 26.8% of patients, whereas severe DDIs were rare (0.2%). Almost all (96.7%) used at least one FRID, and nearly half (46.8%) had an anticholinergic score ≥ 3. Conclusions: DOACs are frequently prescribed together with medications that increase the risk of falls and bleeding. These findings highlight the need for individualized risk–benefit evaluations and deprescribing or substituting high impact FRIDS and ACs when clinically appropriate. Full article

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is increasingly recognized as a risk factor for cognitive decline and dementia, independent of clinically apparent stroke. This narrative review synthesizes current evidence on pathophysiological mechanisms linking AF to cognitive decline, including cerebral hypoperfusion, silent cerebral infarction, microembolism, systemic inflammation, and shared vascular risk factors. A structured literature search was conducted in PubMed and ScienceDirect from January 2000 to October 2025, with evidence quality assessed using adapted Newcastle–Ottawa Scale criteria. Observational evidence suggests that oral anticoagulation, particularly with direct oral anticoagulants (DOACs), may be associated with reduced dementia risk compared to no treatment or vitamin K antagonists. However, most intervention studies were not designed with cognitive endpoints as primary outcomes, limiting causal inference. Current evidence supports comprehensive AF management, including guideline-directed anticoagulation, appropriate rhythm or rate control, and aggressive modification of shared risk factors. Atrial fibrillation is consistently associated with increased risk of cognitive decline and dementia through multiple interrelated mechanisms; however, randomized trials with cognitive endpoints are needed to establish causality. Full article

Background and Clinical Significance: Non-bacterial thrombotic endocarditis (NBTE), historically termed marantic endocarditis, is a severe manifestation of cancer-associated hypercoagulability characterized by sterile valvular vegetations and a high risk of systemic embolization. While direct oral anticoagulants (DOACs) have become the standard of care for cancer-associated venous thromboembolism (CAT), their efficacy in preventing high-shear arterial thrombosis in NBTE has been contested. Emerging data suggest that DOACs may fail to halt vegetation growth in active malignancy, necessitating a reversion to heparin-based therapies. Case Presentation: A 47-year-old female with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) presented with progressive dyspnea and digital ischemia despite strict adherence to therapeutic anticoagulation with rivaroxaban for a prior pulmonary embolism. Echocardiography showed large vegetations on all three cusps of the aortic valve, confirming NBTE. Computed tomography revealed extensive tumor progression. The therapeutic strategy involved an immediate switch from rivaroxaban to therapeutic low-molecular-weight heparin (LMWH) and the initiation of dual targeted therapy with selpercatinib and tepotinib. Serial transesophageal echocardiography documented regression within two weeks and eventual complete resolution of the valvular vegetations after eight weeks, occurring in tandem with a rapid radiological response of the tumor. Conclusions: Upon diagnosis of NBTE, a rapid oncologic work-up is warranted, as ongoing tumor progression is highly likely. This case questions the appropriateness of direct oral anticoagulants in patients with NBTE and active, progressive malignancy. Full article

A significant clinical challenge is represented by the use of anticoagulants in patients with chronic liver diseases—such as metabolic steatohepatitis (MASH), metabolic associated steatotic liver disease (MASLD), and liver cirrhosis (LC). There is a well-established association between alcohol-related LC and atrial fibrillation (AF). These individuals often require anticoagulation, but treatment must carefully balance the heightened risks of both thrombosis and bleeding. Direct oral anticoagulants (DOACs) are recognized as effective and safe alternatives to warfarin, offering superior stroke prevention and a more favorable safety profile regarding major bleeding. They are generally considered safe for use in patients with LC classified as Child–Pugh A and B—excluding rivaroxaban—but are contraindicated in those with Child–Pugh C cirrhosis. DOACs also offer practical advantages, including convenience of administration, fewer drug interactions, and a high level of safety and efficacy. Comprehensive randomized controlled trials with well-defined cirrhosis stages and standardized anticoagulation protocols are essential to guide clinical decision-making. Until then, a multidisciplinary, individualized approach remains critical in managing patients with both AF and LC. The present review aims to explore the complex interplay between alcohol-related LC and the therapeutic use of direct oral anticoagulants (DOACs), particularly in the presence of cardiovascular risk factors such as atrial fibrillation, and the associated thrombotic complications. Full article

Percutaneous left atrial appendage occlusion (LAAO), patent foramen ovale (PFO) closure, and atrial septal defect (ASD) closure rely on temporary antithrombotic therapy to prevent device-related thrombus during endothelialization, yet optimal regimens remain uncertain and vary widely across clinical practice. This review synthesizes contemporary evidence on postprocedural antithrombotic strategies, comparing efficacy and safety data and identifying key gaps in knowledge. After LAAO, therapeutic approaches range from short-term anticoagulation with vitamin K antagonists or direct oral anticoagulants to dual or single antiplatelet therapy in patients with high bleeding risk; observational data increasingly support DOAC-based regimens, although device-related thrombus remains a significant concern, and follow-up imaging protocols are inconsistent. Following PFO and ASD closure, antiplatelet-only regimens—typically brief dual antiplatelet therapy followed by aspirin—are widely used, with evidence suggesting that simplified or abbreviated strategies may be sufficient in selected patients. Despite extensive clinical experience, high-quality comparative trials are limited, and optimal therapy, duration, and surveillance remain debated. Standardized imaging definitions, randomized studies, and individualized risk-based frameworks are needed to optimize antithrombotic care after atrial structural interventions. Full article

Background: Atrial fibrillation (AF) is consistently associated with cognitive impairment and dementia through mechanisms that extend beyond classical cardioembolic stroke. However, the relative contribution of these pathways and the effectiveness of available therapeutic strategies for preserving cognition remain uncertain, as most data come from observational studies with a substantial risk of bias. Objectives: This review narratively synthesizes contemporary evidence on epidemiology, pathophysiological mechanisms, therapeutic strategies—including anticoagulation, rhythm control, and comprehensive risk-factor management—and the role of digital health technologies in the relationship between AF and cognitive decline. Methods: We performed a narrative, PRISMA-informed scoping review of observational cohorts, mechanistic studies, randomized clinical trials, systematic reviews, and meta-analyses published up to January 2026, identified through structured searches in MEDLINE/PubMed and complementary sources. Studies were selected if they examined (i) associations between AF and cognitive impairment or dementia, (ii) mechanistic pathways linking AF to brain injury, (iii) therapeutic interventions with cognitive or brain imaging outcomes, or (iv) digital health technologies applied to AF management. Heterogeneity in study design and outcome assessment precluded meta-analysis; therefore, we provide a qualitative synthesis, explicitly distinguishing observational evidence from randomized data and discussing key sources of confounding. Risk of bias was evaluated using validated tools: ROBINS-I for non-randomized studies, RoB 2.0 for RCTs, Newcastle–Ottawa Scale for observational cohorts, and AMSTAR-2 for systematic reviews. Results: Large population-based cohorts and meta-analyses indicate that AF is associated with a 1.4–2.2-fold higher risk of cognitive impairment or incident dementia, even after adjustment for shared vascular risk factors and exclusion of patients with prior stroke; nevertheless, residual confounding and selection bias cannot be excluded. Silent cerebral infarcts are detected in roughly one-quarter to two-fifths of AF patients without clinical stroke and are themselves associated with cognitive deficits, suggesting that subclinical embolism represents one important, but not exclusive, pathway. Additional mechanisms include chronic cerebral hypoperfusion, neuroinflammation, small vessel disease, and structural brain atrophy, all of which are incompletely disentangled from comorbidities. Observational data suggest that oral anticoagulation, particularly with direct oral anticoagulants (DOACs), is associated with lower rates of dementia compared with no anticoagulation or warfarin, but randomized trials such as BRAIN-AF and GIRAF have not demonstrated a clear cognitive benefit, underlining the low-to-moderate certainty of this evidence. Rhythm-control interventions, especially catheter ablation, are associated with lower dementia incidence in registry studies, yet strong selection effects and short follow-up limit causal inference. Digital health tools and ABC-pathway mobile applications improve cardiovascular outcomes and adherence, although cognitive endpoints remain largely unexplored. Conclusions: AF should be conceptualized as a neurovascular condition with important implications for brain health, rather than a purely cardiac rhythm disorder confined to stroke prevention. A comprehensive heart–brain management strategy that combines optimal anticoagulation, individualized rhythm control, aggressive vascular risk factor modification, routine cognitive screening in older or high-risk patients, and judicious use of digital health technologies may offer the best opportunity for preserving cognition, although rigorous trials with cognitive endpoints are still needed to establish causality. Full article

Venous thromboembolism (VTE) remains a major cause of morbidity and mortality globally. The incidence of VTE continues to increase over time, contributed to by demographic shifts and emerging risk factors, such as novel cancer treatments and exposure to gender-affirming hormonal therapies. While the introduction of direct oral anticoagulants (DOACs) revolutionized VTE management, increasing complexity in select patient cohorts has driven the need for alternative treatment strategies, including pharmacological and interventional approaches. Concurrently, contemporary patient populations have exposed limitations in existing risk assessment models, highlighting the need for revision and consideration of novel biomarkers. In this review, we provide an overview of the changing VTE landscape, highlighting emerging risk factors, advances in treatment, and the utility of current risk stratification tools and novel biomarkers in guiding care. Full article

Cancer-associated venous thromboembolism (CA-VTE) is a significant complication in oncology, contributing to morbidity, mortality, and increased healthcare utilization. Due to multiple patient- and disease-related factors, patients with cancer are at a markedly elevated risk for VTE, particularly within the first 6 months of diagnosis. The aim of this review is to provide an overview of current challenges and unmet needs in CA-VTE prediction, prevention and management. While the Khorana score remains the most widely used risk stratification tool, its limited sensitivity has prompted the development of more refined models such as PROTECHT, CONKO, ONKOTEV, Vienna-CATS, and COMPASS-CAT. These models incorporate additional clinical variables including cancer subtype, systemic therapies, comorbidities, and emerging biomarkers. However important gaps remain, particularly in addressing bleeding risk, underrepresented racial/ethnic groups, and adapting to novel cancer therapeutics. Recent clinical trials (AVERT, CASSINI) have supported the use of direct oral anticoagulants (DOACs) for primary and secondary prophylaxis in select high-risk populations. However, anticoagulation strategies in complex populations, including those with thrombocytopenia, brain tumors, or concurrent antiplatelet therapy, remain areas of active investigation. Future directions include the integration of genomics, proteomics, and machine learning into risk modeling to enable precision medicine approaches. Ongoing clinical trials are testing the promise of safer prophylactic and therapeutic strategies. Personalized risk assessment and treatment of CA-VTE remain essential to improving patient outcomes in oncology. By consolidating existing evidence and identifying key unmet needs, this review seeks to guide more personalized and effective management of CA-VTE. Full article

Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical management of ACHD and concomitant genetically determined syndromes enrolled in a prospective HF-focused registry. Methods: The PATHFINDER-CHD Registry is a German-based (est. 2022) multicenter observational registry. This web-based platform consecutively tracks ACHD patients across the heart failure spectrum, including those with current or prior HF, as well as those at high structural or functional risk. HF stage was classified using a modified ACC/AHA scheme adapted for CHD; functional capacity was graded according to the Perloff classification. Baseline demographics, CHD anatomy, prior surgical/interventional treatment, cardiac and extracardiac comorbidities, and medication were collected from medical records. Results: Among 1987 enrolled ACHD, 107 (5.4%) had a genetic syndrome (n = 65, 60.7% women; mean age 33.5 ± 9.4 years; range 18–68). Most common syndromes were trisomy 21 (n = 49; 45.8%) and 22q11.2 deletion (n = 27; 25.2%); 31 patients (30.0) had rarer syndromes. Predominant CHD diagnoses were atrioventricular septal defect (n = 42, 39.3%), tetralogy of Fallot (n = 19, 17.8%), and pulmonary atresia with ventricular septal defect (n = 7, 6.5%). A systemic left ventricle was present in 102 (95.3%); 40 (37.4%) had primarily cyanotic CHD, and 7 (6.5%) an Eisenmenger physiology. Most patients (n = 71; 66.4%) had undergone definite surgical repair; 25 patients (23.3%) had at least one catheter intervention, including transcatheter valve implantation in 17 cases (15.9%). HF stage was mainly B (n = 30, 28.0%) or C (n = 75, 70.1%). Perloff functional class I/II was present in 97 (90.7%). Leading cardiac comorbidities included intrinsic aortopathy (n = 49, 45.8%), pulmonary arterial hypertension (n = 12, 11.2%), and arrhythmias (n = 10, 9.3%). Frequent extracardiac comorbidities were thyroid dysfunction (n = 34, 31.8%), kidney disease (n = 16, 15.0%), hyperuricemia (n = 13, 12.1%), and depression (n = 15, 14.0%). Pharmacotherapy was used in 66 patients (61.7%). Beta-blockers (n = 25, 23.4%) were common, while ACEi/ARB (n = 9, 8.4%), diuretics (n = 10, 9.3%), MRAs (n = 8, 7.5%), and SGLT2 inhibitors (n = 3; 2.8%) were infrequently prescribed; no patient received ARNI or digitalis. For targeted treatment of pulmonary arterial hypertension, phosphodiesterase-5 inhibitors (n = 7, 6.5%), endothelin receptor antagonists (n = 6, 5.6%), or prostacyclin analogues (n = 1, 0.9%) were used. As oral anticoagulants, vitamin K antagonists or direct oral anticoagulants (DOACs) were prescribed in 17 cases (15.9%). Forty-one patients (38.3%) received thyroid hormone replacement. Conclusions: Syndromic ACHD constitute a small but clinically high-risk subgroup within an HF-oriented registry, marked by complex CHD, substantial cardio–extracardiac multimorbidity (notably aortopathy, PAH, thyroid disease, renal dysfunction, depression), and low utilization of contemporary HF therapies. These data support specialized, interdisciplinary, longitudinal care pathways and prospective studies addressing outcomes and evidence-based HF management in syndromic ACHD. Full article

Background and Clinical Significance: Left ventricular thrombus formation after acute coronary syndrome represents a severe complication. Comprehensive echocardiographic assessment of the entire ventricle is essential, as regional wall motion abnormalities predispose to thrombus development. Although vitamin K antagonists have traditionally been the cornerstone of therapy, the convenience of direct oral anticoagulants has made them increasingly popular. However, the paucity of prospective data raises concerns regarding their general interchangeability. Case Presentation: We present a case of a basal left ventricular thrombus that rapidly progressed in size despite triple antithrombotic therapy including Apixaban. Conclusions: Following ACS, regional LV dysfunction predisposes to LVT formation—even in patients with only mild to moderate systolic impairment or non-apical akinesia. Although rare, LVT may also develop in basal and mid-ventricular segments. Anticoagulant selection should remain individualized, and short-term follow-up imaging is necessary to monitor therapeutic response. Full article

Background and objectives: Research into clinicians’ and pharmacists’ experiences and perspectives on direct oral anticoagulant (DOAC) use in Saudi Arabia and the broader Middle Eastern area is limited. Therefore, we aimed to evaluate the perspectives and experiences of physicians and pharmacists practicing in Saudi Arabia who prescribe DOACs and dispense DOAC therapy, respectively. Methods: A cross-sectional study was undertaken utilizing an online survey instrument. We collected data via Google Forms. Between June and July 2024, the study questionnaire was distributed to community pharmacists, general practitioners [GPs], cardiologists, residents in internal medicine, and hospital pharmacists (primary and secondary healthcare professionals) working in Saudi Arabia. Results: Comprising 146 doctors and 167 pharmacists, 313 total healthcare professionals participated in the study. Of the weekly DOAC prescriptions, cardiologists had the most at 35%; internal medicine residents came next at 16.3% and general practitioners at 17.5%. Among pharmacists, 16.7% of community pharmacists and 23.9% of hospital pharmacists dispensed DOACs weekly. The most often prescribed and dispensed medications were rivaroxaban, edoxaban, and apixaban. Across all categories, Lexicomp was the most often used tool. Most physicians (98%) said they lowered the DOAC dose when necessary. Especially in dosing, preoperative care, patient education, and medication interaction identification, internal medicine residents and hospital pharmacists expressed more confidence in managing DOACs. In these domains, community pharmacists expressed less trust. Conclusions: This study revealed that most participants preferred newer oral anticoagulants over warfarin and demonstrated a fairly good level of self-perceived knowledge regarding various aspects of the clinical use of DOACs. The study findings highlight the importance of focused training initiatives to standardize the use of DOACs, boost trust among community pharmacists and GPs, and ensure safe and effective patient care. Full article