Search Results (442)

Objectives: To evaluate the association between antidepressant use and the risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism (PE), through a systematic review and meta-analysis of observational studies. Methods: A comprehensive literature search was conducted in Medline, Embase^®, and Web of Science^® up to December 2024. Eighteen studies (cohort, case-control, and nested case-control designs) meeting inclusion criteria were analyzed. Study quality was assessed using the Newcastle–Ottawa Scale. Pooled relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses were performed based on recency of antidepressant use, VTE onset type (first vs. recurrent), and VTE subtype (PE). Results: Antidepressant use was associated with a significantly increased risk of VTE (RR = 1.22; 95% CI: 1.12–1.32; p < 0.001). Subgroup analyses revealed a stronger association for recent use (within 90 days), first-onset VTE, recurrent VTE, and PE. Heterogeneity was high (I² = 87.92%), but sensitivity analysis confirmed result robustness. No publication bias was detected. Conclusions: This meta-analysis indicates a modest but statistically significant increase in the risk of VTE associated with antidepressant use, particularly among recent users, individuals experiencing either first-time or recurrent VTE, and those with PE-type events. These findings highlight the importance of individualized VTE risk assessment when initiating antidepressant therapy. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease characterized by chronic inflammation, vascular remodeling, and immune dysregulation. COVID-19, caused by SARS-CoV-2, shares several systemic immunohematologic disturbances with IPF, including cytokine storms, endothelial injury, and prothrombotic states. Unlike general comparisons of viral infections and chronic lung disease, this review offers a focused analysis of the shared hematologic and immunologic mechanisms between COVID-19 and IPF. Our aim is to better understand how SARS-CoV-2 infection may worsen disease progression in IPF and identify converging pathophysiological pathways that may inform clinical management. We conducted a narrative synthesis of the peer-reviewed literature from PubMed, Scopus, and Web of Science, focusing on clinical, experimental, and pathological studies addressing immune and coagulation abnormalities in both COVID-19 and IPF. Both diseases exhibit significant overlap in inflammatory and fibrotic signaling, particularly via the TGF-β, IL-6, and TNF-α pathways. COVID-19 amplifies coagulation disturbances and endothelial dysfunction already present in IPF, promoting microvascular thrombosis and acute exacerbations. Myeloid cell overactivation, impaired lymphocyte responses, and fibroblast proliferation are central to this shared pathophysiology. These synergistic mechanisms may accelerate fibrosis and increase mortality risk in IPF patients infected with SARS-CoV-2. This review proposes an integrative framework for understanding the hematologic and immunologic convergence of COVID-19 and IPF. Such insights are essential for refining therapeutic targets, improving prognostic stratification, and guiding early interventions in this high-risk population. Full article

Despite the prevalence of fucosylated IgG in plasma, specific IgGs with low core fucosylation sporadically emerge in response to virus infections and blood cell alloantigens. This low fucosylation of IgG is implicated in the pathogenesis of SARS-CoV-2 and dengue infections. In COVID-19, the presence of IgGs with low core fucosylation (afucosylated IgGs) targeting spike protein predicts disease progression to a severe form and actively mediates this progression. This study reveals that SARS-CoV-2 infection of megakaryocytes promotes the generation of pathogenic afucosylated anti-spike IgGs, leading to outcomes, such as pulmonary vascular thrombosis, acute lung injury, and mortality in FcγRIIa-transgenic mice. Platelets from mice injected with virus-infected human megakaryocytes express significant activation biomarkers, indicating a direct link between the immune response and platelet activation. Mice injected with virus-infected human megakaryocytes demonstrate an elevated rate of thrombus formation induced by FeCl₃ (4%) and a reduction in bleeding time, emphasizing the intricate interplay of viral infection, immune response, and hemostatic complications. Treatment with inhibitors targeting FcγRIIa, serotonin, or complement anaphylatoxins of mice injected with spike-expressing MKs successfully prevents observed platelet activation, thrombus formation, and bleeding abnormalities, offering potential therapeutic strategies for managing severe outcomes associated with afucosylated IgGs in COVID-19 and related disorders. Full article

Background: The optimal anticoagulation strategy for obese patients with superficial vein thrombosis (SVT) remains unclear. This study evaluates the impact of obesity on anticoagulation patterns and clinical outcomes in patients with lower limb SVT. Methods: We conducted a prospective observational study including consecutive patients with SVT in a tertiary hospital from 2014 to 2024. Patients with SVT ≥ 5 cm in length and ≥3 cm from the saphenofemoral junction were included. Obese (BMI ≥ 30) and non-obese (BMI < 30) patients were compared. Patients were followed for one year. Outcomes were assessed at 90 and 365 days. The primary outcomes were venous thromboembolism (VTE) recurrence (SVT, deep vein thrombosis [DVT], or pulmonary embolism [PE]). The secondary outcomes were major bleeding and all-cause mortality. Results: Of 136 patients, 58 (42.6%) were obese. Both groups had similar baseline characteristics, except for younger age and higher smoking prevalence in obese patients. Most patients received anticoagulation (91.9%), primarily a prophylactic dose of low molecular weight heparin or a prophylactic dose of fondaparinux. No significant differences were found in VTE recurrence at 90 or 365 days (p = 0.505), and no major bleeding events occurred. Female sex was associated with a higher risk of VTE recurrence (OR 4.33, 95% CI 1.17–15.98, p = 0.028), but obesity did not influence outcomes. Conclusions: Obesity was not associated with increased VTE recurrence in patients with lower limb SVT. No major bleeding events were observed. These findings suggest that standard anticoagulation regimens may be appropriate for obese patients with SVT, but further studies are needed to confirm these results. Full article

Pulmonary embolism (PE) is an under-recognised yet serious complication in patients with acute ischaemic stroke (AIS), contributing significantly to morbidity and mortality. The interplay of traditional risk factors—such as immobility, endothelial dysfunction, and hypercoagulability—with AIS-specific conditions, including atrial fibrillation, malignancy, and reperfusion therapies, complicates both diagnosis and management. Despite available prophylactic strategies, including low-molecular-weight heparin and intermittent pneumatic compression, their use remains limited by bleeding concerns and a lack of tailored guidelines. This review synthesises the current evidence on the incidence, risk factors, pathophysiology, diagnostic approaches, and preventive strategies for PE in AIS, identifying critical gaps in risk stratification and clinical decision-making. We propose a novel mechanistic framework—the Brain–Lung Thromboinflammatory Axis Hypothesis—which posits that stroke-induced systemic inflammation, neutrophil extracellular trap (NET) formation, and pulmonary endothelial activation may drive in situ pulmonary thrombosis independent of deep vein thrombosis. This conceptual model highlights new diagnostic and therapeutic targets and underscores the need for stroke-specific VTE risk calculators, biomarker-guided prophylaxis, and prospective trials to optimise prevention and outcomes in this vulnerable population. Full article

Venous thromboembolism (VTE) represents a significant complication of cancer immunotherapy, with emerging evidence suggesting distinct pathophysiological mechanisms compared to traditional chemotherapy-associated thrombosis. This narrative review examines the epidemiology and pathogenesis of VTE in patients receiving immunotherapies for cancer including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, bispecific T-cell engagers (BiTEs), among others. Real-world studies demonstrate a wide range of VTE incidence rates in ICI recipients, with potential mechanisms including exacerbated underlying interleukin-8-mediated inflammatory pathways and consequent neutrophil extracellular trap (NET) formation. CAR T-cell therapy is associated with unique hemostatic challenges, including concurrent thrombotic and bleeding risks related to cytokine release syndrome. Current risk assessment tools show limited predictive utility in patients receiving immunotherapies for cancer, highlighting the need for novel stratification models. Future research priorities include developing immunotherapy-specific risk prediction tools, elucidating mechanistic pathways linking immune activation to thrombosis, and establishing evidence-based and tailored thromboprophylaxis strategies. As cancer immunotherapy continues to evolve, understanding and mitigating thrombotic complications remains crucial for optimizing patient outcomes. Full article

The COVID-19 pandemic has significantly impacted global health, with pulmonary embolism (PE) emerging as a critical complication due to the hypercoagulable state induced by SARS-CoV-2 infection. Despite advancements in prevention and treatment, PE remains a major cause of morbidity and mortality in COVID-19 patients. This study analyzes the trends, outcomes, and contributing factors of PE across ten pandemic waves in Romania, highlighting the evolving clinical burden and management approaches. This retrospective observational study was conducted on confirmed COVID-19 patients that also developed PE, who were admitted to “Victor Babeș” Hospital and Municipal Emergency Hospital in Timișoara, Romania. Data on demographics, clinical features, inflammatory markers, comorbidities, and treatment were collected from medical records. Statistical analyses, including ANOVA and Kaplan–Meier survival analysis, were conducted to evaluate trends and survival outcomes over time. The study included 166 patients, with a mean age of 67.26 ± 13.57 years. Mortality peaked at 50% in Wave 1, declined to 12% in Wave 7, and increased again to 28% in Wave 10. Intubation rates varied, with a high of 29% in Wave 6 and a low of 12% in Wave 8. Lung involvement was the most severe in Wave 4 (mean 0.54 ± 0.18) but improved in later waves, reaching a mean of 0.24 ± 0.12 in Wave 8. This study highlights the dynamic trends in PE during the COVID-19 pandemic in Romania. Improved clinical management, vaccination, and adaptive healthcare strategies contributed to better outcomes in later waves. Full article

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a life-threatening vascular disorder associated with significant morbidity and mortality. Prompt diagnosis is crucial for preventing fatal complications. Current clinical VTE diagnosis predominantly relies on imaging modalities such as compression ultrasound, computed tomography angiography (CTA), and magnetic resonance imaging (MRI). However, these techniques are resource-intensive, time-consuming, and may expose patients to radiation risks. Consequently, the development of highly sensitive and specific biomarkers is imperative to enhance early detection and guide therapeutic interventions. This review examines established and emerging biomarkers in venous thrombosis, evaluates current challenges, and outlines promising future directions for biomarker research in VTE. Full article

Background: Chronic kidney disease (CKD) and its advanced stage, end-stage renal disease (ESRD), affect millions worldwide and are associated with a paradoxical hemostatic imbalance—marked by both increased thrombotic and bleeding risks—which complicates anticoagulant use and demands clearer, evidence-based clinical guidance. Design: This study is a critical review synthesizing the current literature on anticoagulant therapy in CKD and ESRD, with emphasis on altered pharmacokinetics, clinical complications, and therapeutic adjustments. Data Sources: PubMed, Scopus, and Google Scholar were searched for articles discussing anticoagulation in CKD/ESRD, focusing on pharmacokinetics, clinical outcomes, and dosing recommendations. Study Selection: Studies examining the safety, efficacy, and pharmacokinetics of anticoagulants—including heparin, low-molecular-weight heparin (LMWH), warfarin, and direct oral anticoagulants (DOACs)—in CKD and ESRD populations were included. Data Extraction and Synthesis: Key findings were summarized to highlight the dose modifications, therapeutic considerations, and clinical challenges in managing anticoagulation in CKD/patients with ESRD. Emphasis was placed on balancing thrombotic and bleeding risks and identifying gaps in existing guidelines. Results: Patients with CKD and ESRD exhibit a paradoxical hypercoagulable state marked by platelet dysfunction, altered coagulation factors, and vascular endothelial damage. This condition increases the risk of thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), while simultaneously elevating bleeding risks. Hemodialysis and CKD-associated variables further complicate the management of coagulation. Among anticoagulants, unfractionated heparin (UFH) is preferred due to its short half-life and adjustability based on activated partial thromboplastin time (aPTT). Low-molecular-weight heparins (LMWHs) offer predictable pharmacokinetics but require dose adjustments in CKD stages 4 and 5 due to reduced clearance. Warfarin necessitates careful dosing based on the estimated glomerular filtration rate (eGFR) to maintain an international normalized ratio (INR) ≤ 4, minimizing bleeding risks. Direct oral anticoagulants (DOACs), particularly Apixaban, are recommended for patients with eGFR < 15 mL/min or those on dialysis, although data on other DOACs in CKD remain limited. The lack of comprehensive guidelines for anticoagulant use in CKD and ESRD highlights the need for individualized, patient-centered approaches that account for comorbidities, genetics, and clinical context. Conclusions: Managing anticoagulation in CKD/ESRD is challenging due to complex coagulation profiles and altered pharmacokinetics. Judicious dosing, close monitoring, and patient-centered care are critical. High-quality randomized controlled trials are needed to establish clear guidelines and optimize therapy for this vulnerable population. Full article

Since the initial reports of Long COVID symptoms, numerous pathophysiological mechanisms have been proposed to explain them; nevertheless, no consensus has been reached. Some of these mechanisms are directly linked to microcirculation, while others are related indirectly. Those with a direct connection involve the respiratory system (such as pulmonary embolism), the cardiovascular system (including cardiac arrest, heart failure, myocardial inflammation, stroke, endothelial dysfunction, and microangiopathy), hematological conditions (like coagulopathy, deep vein thrombosis, microclots, and endothelial irregularities), and brain function. However, few of these mechanisms are grounded in quantitative data and fundamental physiological principles. Furthermore, diagnostic and therapeutic methods remain inadequate. This report provides a brief overview of these processes, focusing primarily on quantitative data, recently proposed mechanisms, and advances in microcirculation, with a special emphasis on the tissue blood supply reduction (TBSR or SR in short) mechanism. Then, the SR pathophysiological mechanism is assessed based on the total incidence rate of the Long COVID symptoms that can be directly attributed to this mechanism. The proposed SR mechanism can account for seven principal Long COVID symptoms with a total normalized incidence of 76%. Full article

Pulmonary arterial hypertension (PAH) is a lethal condition marked by the proliferation and remodeling of small pulmonary arteries, ultimately leading to right ventricular hypertrophy and right heart failure. PAH secondary to connective tissue diseases (CTDs) is a progressive complication with a complex pathogenesis that results in the reduced efficacy of vasodilation-based therapies and poor clinical outcomes. Systemic sclerosis is the most commonly associated CTD with PAH in Western countries and has been most extensively investigated. Systemic lupus erythematosus and other CTDs may also be associated with PAH; however, they are less studied. In this review, we explore the general pathobiology of PAH, with a particular emphasis on recent advances in the molecular pathogenesis of CTD-PAH, including endothelial cell dysfunction, dysregulated cell proliferation and vascular remodeling, extracellular matrix remodeling, in situ thrombosis, right ventricular dysfunction, genetic aberrations, and immune dysregulation. We also conduct a thorough investigation into the potential serum biomarkers and immune dysregulation associated with CTD-PAH, summarizing the associated autoantibodies, cytokines, and chemokines. Furthermore, relevant animal models that may help unravel the pathogenesis and contribute to the development of new treatments are also reviewed. Full article

Background/Objectives: Thrombotic diseases (TDs), currently the number one killer worldwide, account for the highest mortality rate globally. In this study, we evaluated the antithrombotic efficacy of Velefibrinase, a marine bacteria-derived fibrinolytic enzyme, across multiple animal models. Results: The results demonstrated that Velefibrinase prolonged bleeding time (BT) and clotting time (CT), reduced mortality and thrombosis, relieved pulmonary alveolar structure degeneration in an acute pulmonary thromboembolism model, and inhibited carotid artery thrombosis and endothelial tissue damage in a rat model of FeCl₃-induced carotid arterial thrombosis. Moreover, Velefibrinase reduced cerebral ischemia volume and ameliorated neurological deficits in a cerebral ischemia/reperfusion (I/R) injury model in rats. The putative underlying mechanisms were found to involve the inhibition of platelet aggregation and coagulation, along with the modulation of oxidative stress and inflammation levels. Conclusions: These results revealed that Velefibrinase exerts a notable thrombosis-preventive effect by interacting with multiple targets, thereby breaking the vicious cycle involving inflammation, oxidative stress, and thrombosis. Full article

Background: Internal jugular vein thrombosis (IJVT) is a rare but serious complication in hospitalized patients, often associated with central venous access devices (CVADs). The primary objective of the study was to analyze the clinical characteristics of patients with newly diagnosed IJVT, in particular to evaluate mortality, development of pulmonary embolism and incidence of bleeding at 30 days from diagnosis. Secondly, a sub-analysis was performed between patients with device-related and non-device-related thrombosis. Methods: Prospective study on adult inpatients diagnosed with IJVT from January to December 2024. Data on demographics, comorbidities, device use, laboratory values at diagnosis (D-dimer, platelet count, C-reactive protein (CRP), liver/renal function), treatment, and outcomes (mortality, pulmonary embolism, bleeding) were collected. Results: Thirty-one patients with IJVT were included. Mean age was 71.0 ± 13.2 years; 54.8% female; 35.5% had CVADs (central venous catheter (CVC) 36.4%, midlines 36.4%, peripherally inserted central catheter (PICC) 27.2%). Device-associated IJVT patients exhibited lower D-dimer (2.1 ± 0.5 vs. 3.6 ± 0.8 µg/mL; p = 0.018), higher platelet counts (249.0 ± 86.7 vs. 184.3 ± 53.6 × 10⁹/L; p = 0.044), and elevated CRP (12.5 ± 9.2 vs. 5.1 ± 5.6 mg/L; p = 0.033). Overall mortality was 16.1%; pulmonary embolism occurred in 16.1% and bleeding in 6.5%. CVAD use was not independently associated with adverse outcomes. Conclusions: IJVT presents with distinct biomarker profiles when associated with CVADs, characterized by lower systemic fibrinolysis and heightened inflammation. Recognition of these differences may refine diagnostic thresholds and guide prophylactic strategies. Larger prospective studies are warranted. Full article

Background: Deep vein thrombosis (DVT) is an important component of venous thromboembolism and can lead to pulmonary embolism with high morbidity and mortality. Anticoagulant therapy alone (AC) and catheter-directed thrombolysis (CDT) are commonly used strategies for the management of DVT. Although CDT has been reported to be effective in reducing the risk of post-thrombotic syndrome (PTS), it remains unclear in which patient groups it should be preferred due to the risk of bleeding. Methods: This retrospective study included 175 patients diagnosed with DVT between 2015 and 2024 (98 AC, 77 CDT). Patients with a diagnosis of proximal DVT, aged ≥18 years, and with at least 30 days of follow-up data were included. The primary endpoint was 30-day mortality and secondary endpoints were the length of hospitalization, pulmonary embolism, and bleeding complications. Results: The CDT group was superior to AC in thrombus clearance rates, especially in iliac vein thrombosis (97.7% vs. 78%, p = 0.003). Clinical symptoms improved faster in the CDT group, but total hospitalization was longer. There were no significant differences in bleeding complications and mortality rates between the two groups. Conclusions: The optimal approach to DVT treatment should be based on the patient’s individual risk factors. Although CDT provides a higher thrombus clearance rate, especially in iliac vein thrombosis, it may not be suitable for all patients. Future large-scale studies will contribute to a better understanding of the long-term outcomes of interventional therapies. Full article

Background: Popliteal venous aneurysms (PVA) are an uncommon but potentially severe condition due to their association with increased risk of recurrent pulmonary embolisms. Because of their rarity, their aetiology, natural history, and optimal treatment strategies have been poorly defined. The aim of this paper is to report a comprehensive systematic review on the treatment strategies and outcomes in PVA, summarizing current evidence. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science, covering studies published from database inception through February 2025 (protocol registered on PROSPERO CRD420251008927). The primary endpoint was the analysis of outcomes and complications associated with surgical and conservative management. Results: Nine studies, including 173 adult patients with popliteal venous aneurysms, were included. The mean age was 56 years (range 18–86 years, mean aneurysm diameter 25.4 mm). Most of the patients were female (73, 42.2%). Overall, 85 (49.1%) aneurysms were saccular and 74 (42.8%) fusiform, although morphology was not consistently reported across all studies. Intraluminal thrombus was reported in 26 cases (15.0%), and pulmonary embolism upon presentation in 21 (12.1%). Surgical treatment was performed in 119 patients (68.8%), while 54 (31.2%) were managed conservatively. Fifteen patients (13.0%) experienced postoperative complications, including wound infections (4, 3.5%), hematomas (7, 6.0%), and nerve injury (4, 3.5%), but no cases of postoperative pulmonary embolisms were observed. Following surgery, anticoagulation was indicated in most cases for 3–6 months or a long life. During follow-up (mean 35 months, range 1–262), thrombosis of the surgical reconstruction was observed in 1 patient (0.8%). Death occurred in 3 cases (5.5%), all in the non-surgical group: 2 (3.7%) due to malignancy and 1 (1.9%) from myocardial infarction. Conclusions: PVA is a rarely described condition potentially associated with the risk of PE. In their management, surgical strategies in association with oral anticoagulation represent the most commonly described approach, allowing for satisfactory results and a low rate of complications. Full article