Search Results (358)

Pulmonary embolism (PE) is one of the most serious complications of antiphospholipid syndrome (APS), a systemic autoimmune disorder defined by thrombotic events and persistent antiphospholipid antibodies (aPLA). PE occurs in 11–20% of patients and may constitute the initial clinical manifestation. Young and middle-aged women are most frequently affected, and triple-positive aPLA profiles markedly increase the risk of recurrence and long-term morbidity, including chronic thromboembolic pulmonary hypertension (CTEPH). This review article summarizes current evidence on the epidemiology, pathophysiology, diagnostic approach, and management of PE in APS. Key mechanisms include anti-β2-glycoprotein I-mediated endothelial and platelet activation, complement engagement, and neutrophil extracellular trap formation, resulting in immunothrombosis. Diagnostic pathways follow standard PE algorithms; however, chronically elevated D-dimer levels and lupus anticoagulant-related aPTT prolongation require careful interpretation and consideration. Long-term vitamin K antagonist therapy remains the standard of care, whereas direct oral anticoagulants are not recommended in high-risk APS. Future directions include improved risk stratification through detailed aPLA profiling and the use of emerging biomarkers, early screening for CTEPH, and the development of targeted therapies such as complement inhibition and anti-NETosis strategies. Full article

Background/Objectives: Hemorrhagic complications are among the most common adverse events of anticoagulant therapy in patients with atrial fibrillation (AF). Non-vitamin K antagonist oral anticoagulants (DOACs) are known to be more effective than vitamin K antagonists (VKAs) in preventing thromboembolism. The aim was to identify clinical factors associated with hemorrhagic events in AF patients treated with DOACs and to develop a simple, clinically applicable bleeding risk score. Methods: Data were derived from the multicenter CRAFT trial (NCT02987062). We conducted a retrospective analysis of hospital records of 1435 AF patients (median age: 67 years; 44.8% female) treated with dabigatran or rivaroxaban. The main study endpoints were the occurrence of a bleeding episode, thromboembolic episode, or all-cause death during a mean four-year follow-up (1531 [1062–2140] days). Results: The rates of bleeding episodes, thromboembolic episodes, and all-cause death were 17.4%, 13.5%, and 23.9%, respectively. Nine factors were identified as predictors of bleeding complications: male sex, history of major bleeding, history of cancer, COPD, CRT, rivaroxaban therapy, statin therapy, age, and absence of heart failure. Based on these, the CRAFT bleeding score was developed to predict the risk of hemorrhagic events in individual patients. Conclusions: The CRAFT bleeding score may be implemented in AF patients as an additional tool for evaluating DOACs safety prior to initiating anticoagulant therapy, and for guiding closer monitoring of high-risk individuals to minimize bleeding complications. Full article

Background/Objectives: Unusual-site venous thrombosis (USVT) lacks robust evidence guiding anticoagulant selection between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). This study aimed to evaluate recanalization, recurrence, and major bleeding outcomes in real-world USVT patients and to replicate these findings through a validated digital twin model with Monte Carlo simulation. Methods: We conducted a retrospective study of 90 USVT patients (72% VKAs, 28% DOACs). A conditional generative adversarial network was used to generate digital twins matched on age, sex, thrombosis site, and malignancy. Logistic regression was applied to estimate treatment-specific outcome probabilities for recanalization, recurrence, and major bleeding. A nested stochastic simulation framework simulated 500 iterations across clinical scenarios, including increased DOAC use, cancer prevalence, cerebral vein thrombosis proportion, and optimized VKA control. Results: The mean age was 67.5 years, and 54.4% were female. 61.1% of splanchnic vein thrombosis, 36.7% of upper extremity deep vein thrombosis, and 2.2% of cerebral vein thrombosis were included. In the real cohort, complete recanalization occurred in 40.0% of patients with DOACs and 36.0% with VKAs. Recurrence was 8.0% with DOACs and 7.7% with VKAs, and major bleeding occurred in 8.0% and 10.8% of cases, respectively. All-cause mortality was 20% in DOAC-treated patients and 60% in those receiving VKAs. Digital Twin-based predictions replicated these results (recanalization 40.3% versus 38.0%; recurrence 10.9% versus 8.6%; bleeding 7.6% versus 9.1%). Simulated scenarios preserved the directionality effect, with the most significant differences observed in high-cerebral vein thrombosis and cancer-enriched patients. Conclusions: DOACs showed comparable efficacy and slightly lower bleeding risk than VKAs in USVT. Digital twin and Monte Carlo modeling provided robust, reproducible simulations of treatment effects under varying clinical conditions. Separating empirical and simulation-based findings, the digital twin supported the internal consistency of real-world observations and demonstrated the potential of in silico modeling as a complementary tool in rare thrombotic diseases. Full article

Background: Anticoagulation in patients with advanced chronic kidney disease (CKD) and atrial fibrillation (AF) remains challenging due to the concurrent risks of thrombosis and bleeding driven by endothelial dysfunction, uremic inflammation, and impaired hemostasis. Evidence comparing vitamin K antagonists (VKAs) with direct oral anticoagulants (NOACs) in this high-risk population, particularly in dialysis, is still limited. Methods: We conducted a single-center, retrospective observational study including 93 patients with CKD stages 4–5 and AF treated between January 2021 and February 2025. Fifty patients received apixaban (2.5–5 mg twice daily), and forty-three received acenocoumarol with a target INR of 2.0–3.0. Thirty-eight patients (41%) were on maintenance hemodialysis. Demographics, comorbidities, and risk scores (CHA₂DS₂-VASc and HAS-BLED) were analyzed. Bleeding events were classified per ISTH criteria. Statistical comparisons used t-tests and χ² tests, with p < 0.05 considered significant. Results: The mean age was 67.8 ± 9.1 years, and 51.6% were male. Major bleeding occurred in 9.7%, minor in 15.8%, and overdose-related bleeding in 10.0% of patients. The overall bleeding rate was significantly lower in the apixaban group (16.0%) than in the acenocoumarol group (53.5%; p = 0.01). No thromboembolic events were observed in either group. Dialysis patients had higher bleeding rates overall (13.2% vs. 7.4%), mainly among those on VKAs. The HAS-BLED score moderately correlated with bleeding incidence (r = 0.43, p < 0.01). Conclusions: Apixaban provided comparable thromboembolic protection with significantly fewer bleeding events than acenocoumarol, including in patients on dialysis. These findings support apixaban as a safer and more practical anticoagulant option in advanced CKD, consistent with its limited renal clearance and reduced influence on the inflammation–coagulation axis. Further multicenter prospective studies are warranted to validate these real-world results. Full article

Pocket hematoma is a common complication following cardiac implantable electronic device (CIED) implantation, traditionally perceived as a manageable local issue. Accumulating evidence, however, indicates that clinically significant pocket hematoma (CSH) is strongly associated with increased infection rates, elevated healthcare costs, and heightened mortality. Key risk factors include advanced age, low body mass index (BMI), chronic kidney disease, complex procedures (device upgrades/replacements) and periprocedural antithrombotic management, particularly uninterrupted dual antiplatelet therapy (DAPT) and heparin/low-molecular-weight heparin (LMWH) bridging strategies, which significantly elevate bleeding risk compared to continued vitamin K antagonist (VKA) therapy or direct oral anticoagulant (DOAC) protocols. Novel compression devices and topical hemostatic agents show promise for prevention, while standardized definitions and risk stratification tools are urgently needed. This review synthesizes current evidence on multifactorial pathogenesis, adverse outcomes, and evolving preventive strategies for pocket hematoma, emphasizing its underappreciated clinical significance and the critical need for optimized periprocedural management in high-risk patients. Full article

Background/Objectives: While direct oral anticoagulants (DOACs) are widely used, robust evidence for low-energy trauma is scarce. Studies have shown similar or better outcomes of traumatic brain injury (TBI) under DOAC therapy compared to vitamin K antagonists, but there is limited data on the differences among DOAC types. Methods: We performed a retrospective study of TBI patients with pre-injury DOACs who presented to our level 1 trauma unit and received cranial computed tomography. Only low-energy trauma mechanisms were included. Results: We included 643 patients with an average age of 82 years. As per the Glasgow Coma Scale, 637 patients (99.1%) had a mild TBI and 34 patients (5.3%) had intracranial hematomas. No delayed intracranial bleeding occurred during in-hospital observation. Rivaroxaban was the most frequent DOAC (278, 43.2%), followed by apixaban (221, 34.4%), dabigatran (84, 13.1%), and edoxaban (60, 9.3%). Neurosurgical interventions were performed in three cases (0.5%). The head injury-related in-hospital mortality was 0.9% (six patients). Fisher’s Exact Test and regression analysis did not demonstrate statistically significant differences among the DOAC types regarding occurrence of intracranial bleeding, surgical interventions, or mortality. Conclusions: We found no statistically significant differences between DOACs regarding complications of TBI after low-energy trauma. This study shows an overall low risk of complications after low-energy trauma in a predominantly geriatric population with TBI and DOAC therapy. Full article

Background: Head trauma is one of the most common causes of morbidity and mortality in emergency departments. It is essential to understand the factors leading to intracranial hemorrhage (IH) in order to improve outcomes and reduce healthcare costs. The aim of this study was to evaluate the factors associated with IH in patients presenting to the emergency department with head trauma. Methods: This prospective observational study was conducted between 27 February 2019 and 27 February 2020 at the emergency department of Eskisehir Osmangazi University. Patients aged ≥18 years with head trauma were included. Data were collected from medical records, with follow-up information obtained via telephone or hospital revisits. Analyses were performed using the chi-squared test in IBM SPSS Statistics (version 21), with p < 0.05 being considered significant. Results: Of the 556 patients, 59.7% were male, and 40.3% were female, with an average age of 45.9 years (SD 21.5). Intracranial hemorrhage (IH) was more prevalent in patients aged over 60 years, with comorbidities, taking medication (especially anticoagulants and non-vitamin K antagonist oral anticoagulants [NOACs]), with altered consciousness, pathological neurological findings or experiencing non-minor trauma. Prolonged activated partial thromboplastin time and new or increased hemorrhage on follow-up CT scans were associated with IH. Conclusions: Advanced age, comorbidities, and anticoagulant use were key factors associated with intracranial hemorrhage (IH) in patients with head trauma. Further studies should assess predictors of mortality and outcomes. Full article

Background: This study aimed to evaluate the efficacy and safety of off-label use of non-vitamin K antagonist oral anticoagulants (NOACs) compared with antiplatelet therapy (APT) in patients with AF-related acute ischemic stroke (AIS) and a glomerular filtration rate (GFR) below 15 mL/min/1.73 m². Methods: We used a multicenter prospective stroke registry to identify patients with AF-related AIS and GFR < 15 mL/min/1.73 m² who were treated with either APT alone or NOAC alone at discharge. Primary outcomes were ischemic stroke recurrence, major bleeding, and all-cause mortality within one year. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Results: Among 311 eligible patients, 135 (43.4%) received APT and 176 (56.6%) received low-dose NOACs. Compared to APT, NOAC use was associated with a significantly lower risk of ischemic stroke recurrence (aHR 0.54, 95% CI 0.29–0.99) but higher risks of major bleeding (aHR 3.25, 95% CI 1.84–5.73) and all-cause mortality (aHR 2.65, 95% CI 1.60–4.38). The most common causes of death were non-vascular events such as sepsis and respiratory failure. Conclusions: In patients with AF-related stroke and ultra-low GFR, off-label use of NOACs may offer a benefit in stroke prevention but is associated with increased risks of bleeding and mortality. These findings suggest the need for individualized treatment strategies and careful monitoring when prescribing NOACs in this vulnerable population. Full article

Background: The management of acute ischemic stroke (AIS) in anticoagulated patients presents a clinical challenge, as concerns about safety and efficacy often limit access to recanalization therapies. Despite the widespread use of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), their impact on functional recovery and mortality following intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) remains uncertain. Therefore, this study investigates the association between prior anticoagulation and 90-day outcomes in AIS patients undergoing reperfusion therapy. Methods: We conducted a retrospective cohort analysis using our institutional stroke registry, including AIS patients admitted to the Department of Neurology at our university between February 2023 and 2025. Anticoagulated patients were 1:1 propensity score-matched with non-anticoagulated controls (n = 126 per group) using Mahalanobis distance matching with a caliper, adjusting for age, sex, hypertension, diabetes, stroke severity (National Institutes of Health Stroke Scale [NIHSS] at admission and 72 h), and pre-stroke functional status (pre-morbid modified Rankin Scale [pre-mRS]). Primary endpoints at 90 days were functional independence (modified Rankin Scale [mRS] ≤ 2), mRS-shift, and mortality (mRS = 6). Predictors of outcome were assessed using multivariable logistic regression and generalized additive models (GAMs). Subgroup analyses evaluated the effects of anticoagulation type and treatment modality. Results: Among 866 AIS patients (DOAC n = 100, VKA n = 48, non-anticoagulated n = 718), 426 (49.2%) underwent reperfusion therapy (IVT n = 195, MT n = 163, IVT + MT n = 68). Before matching, anticoagulated patients were less likely to achieve functional independence (34.5% vs. 52.1%, odds ratio [OR] = 0.48, 95% confidence interval [CI] [0.33–0.70], p < 0.001), had a greater mRS-shift (2.53 vs. 1.79, p < 0.001), and higher mortality (30.4% vs. 14.5%, OR = 2.58, 95% CI [1.72–3.88], p < 0.001). However, after matching, these differences were no longer statistically significant. NIHSS, 72hNIHSS, and pre-mRS were the strongest independent predictors of outcome (p < 0.001), while anticoagulation status had no significant effect. Conclusions: Recanalization therapy was not associated with worse functional outcomes in selected anticoagulated AIS patients. These findings suggest that prior anticoagulation alone should not preclude reperfusion therapy in otherwise eligible patients, and underscore the importance of individualized, evidence-based decision-making in acute stroke care. Full article

The prevalence of atrial fibrillation (AF) is increasing and often coexists with frailty. The management of anticoagulation therapy in frail older adults with AF is especially challenging due to the high risk of bleeding complications. The aim of this narrative review is to provide a comprehensive overview of current evidence about the management of anticoagulation in frail older adults with non-valvular AF. First, frailty itself should not be considered a contraindication. A comprehensive geriatric assessment is recommended to identify and potentially address conditions that may increase the risk of bleeding, such as inappropriately prescribed medications or malnutrition. Overall, the net clinical benefit remains in favour of oral anticoagulation in frail older adults, even if it decreases with increasing frailty severity. Direct Oral Anticoagulants (DOACs) show a better effectiveness and safety profile compared with Vitamin K antagonists (VKAs) in this population. Among DOACs, apixaban seems to be the safest. Also, edoxaban at a very low dosage (15 mg/day) could be an effective therapy in patients for whom the standard anticoagulation is contraindicated. Moreover, switching from VKAs to DOACs in frail older adults is a complex decision and should be personalized according to the stability of the ongoing anticoagulant therapy, the bleeding risk profile, and the severity of frailty. Finally, although further studies are required to confirm their effectiveness, factor XIa inhibitors are emerging as new promising alternative therapies because they have been associated with a lower bleeding risk compared with DOACs. Full article

Background/Objectives: Vitamin D deficiency is highly prevalent worldwide and is associated with multiple comorbidities and pharmacological treatments that may interfere with its metabolism. Evidence on the effect of supplementation across different drug user groups remains limited. Methods: A prospective study was conducted across community pharmacies over twelve months. Baseline socio-demographic, serum 25(OH)D concentration, quality of life (QoL), lifestyle habits, and medication use were collected. Participants received vitamin D supplementation for 12 months. Changes in vitamin D status and QoL were analyzed according to medication use. Logistic regression identified predictors of achieving adequate serum vitamin D levels (>30 ng/mL). Statistical significance was set at p < 0.05. Results: At baseline, 87.2% of 210 participants had insufficient or deficient vitamin D levels. After supplementation, mean serum vitamin D increased significantly from 21.3 ± 8.2 to 32.1 ± 12.6 ng/mL (p < 0.001), and QoL scores improved from 68.6 ± 18.7 to 77.8 ± 18.5 (p < 0.001). Dietary intake of vitamin D–rich foods and outdoor activity also increased. Supplementation improved vitamin D status among users of benzodiazepines, proton pump inhibitors, beta-blockers, statins, levothyroxine, metformin, and angiotensin-converting enzyme inhibitors, but not among corticosteroid, nonsteroidal anti-inflammatory drugs, or vitamin K antagonist. Multivariate analysis confirmed adherence as a strongest predictor of vitamin D adequacy (OR = 15.31, 95% CI = 2.90–80.75), while corticosteroid therapy, diabetes, and hypercholesterolemia were negatively associated. Conclusions: Vitamin D supplementation effectively corrected deficiency and improved QoL, but its efficacy varied according to comorbidities and medication use. Personalized supplementation strategies, emphasizing adherence and considering pharmacological profiles, may optimize outcomes. Further studies should explore mechanistic drug–nutrient interactions and long-term clinical implications. Full article

Introduction: Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder associated with both venous and arterial thrombosis, most notably ischemic stroke. Patients face a high risk of recurrence, and yet optimal strategies for secondary prevention remain uncertain. Methods: We conducted a narrative review of the literature on secondary prevention of ischemic stroke in APS. We performed a comprehensive literature search of PubMed for English-language articles on secondary stroke prevention in APS. Studies were included if they were original human research (e.g., randomized trials, cohort, or case–control studies) or relevant reviews addressing APS-related stroke prevention. Results: Vitamin K antagonists (VKAs) remain the standard of care for high-risk patients with arterial events. Several randomized controlled trials demonstrated higher recurrence rates, particularly of stroke, among APS patients treated with direct oral anticoagulants (DOACs). The optimal target INR remains debated; pooled analyses suggest no clear advantage of high-intensity anticoagulation (INR 3–4) over standard-intensity (INR 2–3), but individualized adjustment is warranted in select cases. In patients with recurrence despite adequate anticoagulation, adding an antiplatelet agent may be beneficial, although supporting evidence is limited. Adjunctive statin therapy shows promise in reducing endothelial dysfunction and prothrombotic markers, with observational data suggesting a possible protective effect, although randomized evidence is lacking. In addition, patent foramen ovale (PFO) closure has been proposed in selected APS patients with paradoxical embolisms, particularly when combined with anticoagulation. Non-pharmacological strategies, including structured lifestyle modification and rigorous vascular risk-factor management, are strongly recommended, as traditional cardiovascular risk factors synergistically increase recurrence risk. Conclusions: Secondary prevention of ischemic stroke in APS requires an individualized approach. VKAs remain first-line, with consideration of antiplatelet add-on, statins, lifestyle interventions, and PFO closure in appropriate settings. Future well-designed clinical trials are needed to refine INR targets, validate combination strategies, and clarify the role of adjunctive therapies in this complex patient population. Full article

Left ventricular thrombus (LVT) remains a clinically significant complication following acute myocardial infarction (MI). Although its incidence has declined in the era of primary percutaneous coronary interventions (PCIs), the best treatment remains unclear. For decades, vitamin K antagonists (VKAs) such as warfarin have been the mainstay of therapy, supported by guidelines recommendations. However, the limitations of warfarin, including a narrow therapeutic range, the need for frequent monitoring, and food/drug interactions, have spurred interest in direct oral anticoagulants (DOACs). This review summarizes the available evidence on anticoagulation strategies for LVT after MI, focusing on observational studies and recent randomized controlled trials. A total of 12 studies were included in this review: 9 retrospective cohorts and 3 randomized controlled trials. Patient populations ranged from small single-center cohorts to large multicenter registries. DOACs, compared with warfarin, were associated with a higher rate of thrombus resolution, a lower rate of stroke and systemic embolism, and a similar mortality. The usage of DOACs marginally reduced the rate of major bleeding compared with warfarin. The current evidence indicates that DOACs may offer comparable efficacy and potentially improved safety relative to warfarin, although most randomized trials remain small and underpowered for definitive conclusions. Larger, adequately powered studies are still required before DOACs can be routinely considered equivalent alternatives. The RIVAWAR randomized trial provides the strongest evidence to date regarding the use of DOACs in LVT after MI, but further large-scale randomized studies are required to establish definitive guidance. Until then, anticoagulation therapy including DOACs should be individualized, balancing the thromboembolic risk, bleeding risk, and practical considerations of anticoagulant use. Full article

Background/Objectives: Pulmonary embolism (PE) remains a leading cause of morbidity and mortality, with outcomes influenced by patient demographics, comorbidities, and anticoagulation strategy. While vitamin K antagonists (VKA) have been standard therapy, direct oral anticoagulants (DOACs) are increasingly adopted, yet real-world data in cancer-associated and non-cancer populations are limited. This study aimed to compare demographics, clinical features, therapeutic strategies, and outcomes between oncologic patients with acute PE (experimental group) and non-cancer patients with PE (control group). Methods: We performed a multicentric retrospective cohort study of adults admitted with acute PE between January 2019 and December 2021. The cohort comprised 120 non-cancer and 106 cancer patients. Standard management was low-molecular-weight heparin with transition to (VKA) or (DOAC), when not contraindicated. Data on demographics, comorbidities, and laboratory biomarkers (including NT-proBNP, threshold 600 pg/mL) were analyzed. Primary outcomes were early (≤30 days) and late (31–365 days) all-cause mortality. Secondary outcomes included PE recurrence and bleeding events. Results: Among 226 PE patients (non-oncological n = 120; oncological n = 106), the cancer group was older (69.2 ± 12.6 vs. 62.6 ± 17.3 years; p = 0.001) with similar ECG findings and hemodynamic stability at presentation. NT-proBNP > 600 pg/mL was more frequent in cancer (37.7% vs. 23.3%; p = 0.018), whereas D-dimer > 5 mg/L was more common in non-cancer (74.2% vs. 55.7%; p = 0.003). DOAC use was lower in cancer patients (40.6% vs. 65.0%; p < 0.001). Early mortality was comparable (17.9% vs. 13.3%; p = 0.341), but late mortality was higher in the cancer patient subgroup (38.7% vs. 3.3%; p < 0.001). In multivariable analysis, belonging to the cancer subgroup was associated with NT-proBNP ≥ 600 (OR 2.08, 95% CI 1.08–4.01; p = 0.029) and older age (OR 1.025 per year, 95% CI 1.005–1.045; p = 0.016), and inversely associated with D-dimer > 5 mg/L (OR 0.35, 95% CI 0.19–0.64; p < 0.001). Conclusions: Prompt anticoagulation was associated with lower early mortality, while differences in late mortality appeared to be largely confounded by age and cancer status. NT-proBNP may serve as a useful risk-stratification biomarker, but confirmation in larger, prospective studies is required. Full article

Background: Hepatocellular carcinoma (HCC) frequently develops in patients with chronic hepatitis B and C. Early detection is critical, but current methods, including ultrasound and AFP, have suboptimal accuracy. Objectives: This study aimed to evaluate the predictive performance of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) testing, alone and in combination, for HCC development. Methods: A retrospective cohort study at a single university center included 242 CHB and 181 CHC patients. Data on demographics, clinical status, laboratory parameters, and imaging were collected, with fibrosis and steatosis assessed by FibroScan^®. Serum AFP and PIVKA-II were measured, but measurements of PIVKA-II in patients receiving vitamin K antagonists were excluded from the analysis. HCC diagnosis and staging followed clinical guidelines. Cox regression and ROC analyses identified independent predictors and evaluated biomarker accuracy for HCC detection. Results: HCC incidence was comparable between cohorts (5.0% in CHB vs. 5.5% in CHC). Both AFP and PIVKA-II independently predicted HCC development in multivariate models adjusted for age and sex. The combined biomarker score (AFP × PIVKA-II) showed superior predictive accuracy with hazard ratios of 1.38 (CHB) and 1.36 (CHC). ROC analyses demonstrated high discriminative ability for PIVKA-II (AUC ~0.81) and AFP (AUC ~0.83) in both cohorts. Additional independent predictors were chronic alcohol abuse, cirrhosis, and higher liver stiffness measurements. Specific viral factors such as HBeAg positivity and HCV subgenotype 1b were also associated with increased HCC risk. Conclusions: AFP and PIVKA-II are independent, valuable biomarkers for HCC risk in chronic hepatitis B and C. Combined use improves early detection, aiding timely treatment. These results support adding PIVKA-II to AFP in surveillance, but larger studies are needed to confirm the findings and refine cut-off values. Full article