Search Results (121)

Background: Pulmonary thromboembolism (PTE) is a preventable yet potentially fatal condition with significant morbidity and mortality. Several clinical scoring systems, including the Wells and modified Geneva scores, have been developed to assess the likelihood of PTE and guide further diagnostic evaluation. The Padua prediction score, primarily used to assess venous thromboembolism (VTE) risk in hospitalized patients, has also been considered for its potential utility in suspected PTE cases. Methods: This retrospective study included 257 patients with suspected acute PTE. Diagnosis was confirmed by computed tomography pulmonary angiography (CTPA) in 140 patients (patient group), while 117 patients without radiologic evidence of PTE served as controls. All participants were evaluated using Wells, modified Geneva, and Padua scores. Sensitivity, specificity, predictive values, and the effect of combining scores with age-adjusted D-dimer levels were analyzed. Results: The Wells score demonstrated a sensitivity of 60% and specificity of 91%, with a positive predictive value of 88%. Modified Geneva and Padua scores showed lower diagnostic accuracy. Negative predictive values increased significantly when combined with age adjusted D-dimer levels. Conclusions: The Wells score was the most reliable tool among the three for predicting PTE. Combining clinical scoring with D-dimer testing enhances diagnostic accuracy and may reduce unnecessary imaging in patients with low to moderate risk. Full article

Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF⁺ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF⁺ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF⁺ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF⁺ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF⁺ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF⁺ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF⁺ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article

Background/Objectives: Patients with chronic kidney disease (CKD) are associated with a significantly elevated cardiovascular risk. The incidence and prevalence of mediated cardiac disorders and major adverse cardiac events (MACEs), such as heart failure, arrhythmias, acute coronary syndrome (ACS) based on coronary artery disease (CAD), stroke, venous thromboembolism, and peripheral artery disease, are significantly higher in CKD patients as compared with the general population. Methods: This narrative review summarizes the current clinical understanding, the pathophysiological mechanisms, and the clinical consequences in the context of cardiovascular risk and disease in CKD. Results: The impact of CKD on mediated cardiovascular disorders and elevated MACE prevalence is complex and multifactorial. The underlying mechanisms involve various traditional cardiovascular risk factors, such as arterial hypertension, smoking, dyslipidemia, and diabetes. Furthermore, CKD-specific molecular and pathophysiological factors, such as chronic inflammation and associated oxidative stress and endothelial cell dysfunction, pro-coagulatory status, uremic toxins and uremic lipids, progressive vascular calcification, and alterations in the regulation of the renin–angiotensin–aldosterone system (RAAS) and sympathetic activation cause an increased cardiovascular risk. Conclusions: Understanding the complex disease mechanisms between CKD and elevated cardiovascular risk might contribute to optimizing individual patients’ risk stratification and result in individualized diagnostic and treatment strategies via appropriate clinical biomarker application and individualized anti-inflammatory approaches. Full article

In recent years, the immune system has emerged as a key player in the development of atherosclerosis, heart failure, venous thromboembolism, and systemic hypertension. Obesity and related cardiovascular diseases (CVDs) remain the leading global cause of death. Adipokines—hormones produced by adipose tissue—exert diverse endocrine and immunomodulatory effects. Among them, chemerin, discovered in the early 20th century, is a chemotactic molecule that recruits dendritic cells, endothelial cells, macrophages, and lymphocytes during early immune responses. It regulates cell migration and vascular homeostasis. Dysregulated adipokine profiles contribute to chronic inflammation, insulin resistance, metabolic syndrome, and impaired blood pressure control. This review explores chemerin’s potential role in CVD pathogenesis, focusing on its immunomodulatory functions, impact on vascular inflammation, and endothelial dysfunction. The presented work also examines recent findings on chemerin’s diagnostic and therapeutic potential in cardiovascular health. Full article

Background: Lymphomas account for approximately 10% of cancers diagnosed during pregnancy, with Hodgkin’s lymphoma being the most common. However, non-Hodgkin lymphomas, including primary mediastinal large B-cell lymphoma (PMBCL), also represent a significant proportion. Both mediastinal lymphomas and pregnancy develop a hypercoagulable state, increasing the risk of venous thromboembolism and massive pulmonary embolism (PE), requiring extracorporeal membrane oxygenation (ECMO). Methods: Clinical data, blood test and imagings have been collected by the medical records of the patient. Results: We present a 25-year-old woman, at 32 weeks of gestation, who presented to the emergency department with progressive dyspnea and asthenia. Echocardiography revealed a hemodynamically significant pericardial effusion and severe right ventricular dysfunction. Given the severity of her condition, she underwent an emergency caesarean section and subsequently a pericardial drainage. A chest computed tomography scan revealed an incidental mediastinal mass along with a massive PE. Despite pericardial drainage, she remained hemodynamically unstable. Since thrombolysis was contraindicated for the recent cesarean section, venoarterial ECMO was initiated. Systemic anticoagulation was guaranteed by heparin, which shifted to argatroban for heparin resistance. The mediastinal mass was also biopsied, and the diagnosis of PMBCL carried out. Cytoreductive chemotherapy was initiated with the COMP-R regimen (i.e., cyclophosphamide, vincristine, methotrexate, prednisone, and rituximab), and the patient progressively improved up to ICU and hospital discharge. Conclusions: This case highlights the challenges in managing a complicated patient requiring early multidisciplinary intervention, which was crucial for stabilizing the patient and optimizing fetal and maternal prognosis. Full article

According to the literature, cardiovascular diseases (CVDs)—including myocardial infarction, stroke, and venous thromboembolism (VTE)—are among the leading causes of mortality and morbidity worldwide. Evidence suggests that CVDs share common risk factors and pathophysiological mechanisms. Similar to the Mosaic Theory of Hypertension proposed by Irvine Page in 1949, the pathophysiology of VTE is multifactorial, involving multiple interacting processes. The concept of immunothrombosis, introduced by Engelmann and Massberg in 2009, describes the interplay between the immune system and thrombosis. Both thrombosis and hemostasis share core mechanisms, including platelet activation and fibrin formation. Additionally, immune mediators—such as monocytes, neutrophil extracellular traps (NETs), lymphocytes, selectins, and various molecular factors—play a critical role in thrombus formation. This review highlights inflammation as a key risk factor for pulmonary embolism (APE). Immunity is central to the complex interactions among the coagulation cascade, platelets, endothelium, reactive oxygen species (ROS), and genetic factors. Specifically, we examine the roles of the endothelium, immune cells, and microRNAs (miRNAs) in the pathophysiology of APE and explore potential therapeutic targets. This review aims to elucidate the roles of the endothelium, immune cells, and miRNAs in the pathophysiology of APE and explore potential future perspective. Full article

(1) Background: Clinical evidence has raised concerns regarding a potential link between COVID-19 mRNA-based vaccines and the occurrence of thromboembolic events. So far, no research has explored the effects of this possible interaction in cancer patients undergoing active treatment. We leveraged prospective monitoring from the Vax-On-Third-Profile study to examine the development of venous thromboembolism (VTE) after the third dose of mRNA-BNT162b2 (tozinameran) and its association with antibody and lymphocyte responses. (2) Methods: Patients who had received a third dose of tozinameran and had not experienced any VTE in the previous 30 days were eligible. A serological evaluation was conducted before the booster vaccination (timepoint-1) and four weeks thereafter (timepoint-2) to measure antibody titers against the SARS-CoV-2 spike protein, as well as to determine the absolute counts of T-helper cells, T-cytotoxic cells, B cells, and NK cells. Data were acquired from November 2021 to October 2022 and analyzed from November 2022 to October 2023. (3) Results: The present study involved 429 patients who were given a third dose of tozinameran from 26 September to 30 October 2021. Among the active treatments of interest, 109 (25.4%) patients received targeted therapy, 111 (25.9%) received cytotoxic chemotherapy, 39 (9.1%) received immune checkpoint inhibitors, 21 (4.9%) received endocrine therapy, and 30 (7.0%) received a combination of chemotherapy and targeted agents in the eight weeks preceding the booster dosing. In addition, 119 (27.7%) patients who had discontinued any systemic therapy for at least 12 weeks accounted for the reference subgroup. After a median follow-up time of 10.6 (95% CI 8.1–11.7) months, we observed 31 venous thromboembolic events in the general population, for an overall incidence rate of 7.2% (95% CI 5.0–10.1). The median time to VTE development after booster immunization was 99 (95% CI 85–112) days. In a univariate comparison, patients exposed to targeted therapies (11.3% [95% CI 6.0–18.9]; p = 0.030) or immune checkpoint inhibitors (16.2% [95% CI 6.2–32.0]; p = 0.012) had a significantly higher incidence of VTE than the reference cohort (3.4% [95% CI 0.9–8.5]). Univariate analysis of immune responses showed that only dynamic changes pertaining to NK cell distributions correlated significantly with VTE occurrence. Multivariate regression analysis confirmed only a high-level NK cell response (OR 6.10 [9% CI 2.16–17.21]; p = 0.001), a history of thromboembolic events (OR 9.81 [3.99–24.13]; p < 0.001), and the presence of a central venous catheter (OR 5.02 [95% CI 1.84–13.67]; p = 0.002) as independently associated with an increased risk of VTE. (4) Conclusions: This prospective cohort study provides unprecedented evidence that cancer patients have no increased risk of developing VTE after the third dose of tozinameran, regardless of the type of active therapy. The specific pattern of lymphocyte response appears to increase thromboembolic risk, underlying immune dysregulation as a causal cofactor. These findings emphasize the need for additional monitoring after periodic COVID-19 vaccination in cancer patients. Full article

Thrombosis is a critical complication in lymphomas, driven by chronic inflammation. To observe this systemic mechanism, we evaluated inflammatory cytokines, neutrophil and monocyte activation, and platelet function in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Hodgkin lymphoma (HL), with and without thrombosis using ELISA and flow cytometry according to laboratory and clinical data. Interleukin-1β was elevated across lymphomas and inversely correlated with the Khorana score for venous thromboembolism, while increased tumor necrosis factor-alpha (TNF-α) was inversely associated with the International Prognostic Index (IPI) in thrombosis-associated lymphomas. Neutrophil activation was increased in DLBCL, while elevated neutrophil extracellular traps (NETs) biomarkers were inversely consistent with thrombosis and the ThroLy score. NETs were elevated in HL. Classical monocytes were increased in all lymphoma subtypes, with intermediate and tissue factor (TF)-carrying monocytes elevated in DLBCL and HL. Platelet activation was pronounced, with platelet–monocyte aggregates and platelet-associated TF elevated in DLBCL and FL but not HL. P-selectin was increased in lymphomas with thrombosis, aligned with Khorana and ThroLy scores, and reflected clinical stage while inversely correlating with IPI in non-thrombotic lymphomas. These findings highlight distinct thromboinflammatory mechanisms across lymphoma subtypes, providing insights into biomarkers for thrombosis risk and therapeutic targets in lymphoma management. Full article

Tuberculosis (TB) induces a hypercoagulable state characterized by systemic inflammation, endothelial dysfunction, and alterations in the coagulation and fibrinolytic pathways. This review explores the pathophysiological mechanisms underlying hypercoagulability in TB, including increased pro-inflammatory cytokine release, endothelial damage, platelet activation, and reduced anticoagulant and fibrinolytic activity. These factors contribute to an elevated risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), which complicate TB prognosis and treatment. The potential role of adjunctive anti-inflammatory therapies, such as vitamin D, NSAIDs, corticosteroids, and anti-platelet agents, is highlighted as a strategy to mitigate systemic inflammation and reduce thrombotic risks in patients with TB. The challenges of anticoagulation therapy, particularly in managing the interactions between anti-TB medications and traditional anticoagulants, are discussed, along with the potential of novel oral anticoagulants (NOAs) as alternatives. We also address therapy of hypercoagulability in TB within resource-limited settings which requires low-cost diagnostics, accessible anticoagulation options, adjunctive therapies, and preventive strategies integrated into existing healthcare systems. Effective risk stratification and individualized management strategies are vital for reducing the morbidity and mortality associated with thrombotic complications in TB. Full article

Venous thromboembolism (VTE) and arterial thrombosis (AT) are distinct yet closely related pathological processes. While traditionally considered separate entities, accumulating evidence suggests that they share common risk factors, such as inflammation and endothelial dysfunction (ED). This review explores the parallels and differences between venous and arterial thrombosis, with particular attention to the role of unprovoked VTE and its potential links to atherosclerosis and systemic inflammation. A key focus is the role of ED, which is emerging as a critical factor in thrombogenesis across both the venous and arterial systems. We examine the current methods for clinically detecting ED, including the use of biomarkers and advanced imaging techniques. Additionally, we discuss novel research avenues, such as the potential of endothelial colony-forming cells and other innovative methodologies, to further unravel the complex mechanisms of thrombosis. Finally, we propose future clinical scenarios where targeting endothelial health could pave the way for more effective prevention and treatment strategies in thrombosis management. Full article

Improved efficacy has been shown for amivantamab and amivantamab-based combination therapies in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) compared to established treatment options in clinical trials. However, a high risk of venous thromboembolism (VTE) was observed in patients treated with amivantamab-based therapies, with considerable differences in VTE risk according to the line of systemic treatment, concomitant treatment with lazertinib, and intravenous vs. subcutaneous amivantamab administration. Based on early reports of high VTE rates, prophylactic anticoagulation has been implemented in ongoing clinical trials for the first 4 months of amivantamab–lazertinib therapy. However, open questions remain concerning the type, dosing, and duration of primary pharmacological thromboprophylaxis in patients treated with amivantamab-based therapies. Therefore, the aim of this clinical opinion piece is to provide provisional guidance on how to mitigate VTE risk in patients treated with amivantamab-based therapies following existing clinical practice guidelines on primary thromboprophylaxis and treatment of VTE in ambulatory patients with cancer. Full article

Background: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with unique biological characteristics and complications, including thromboembolism. This systematic review evaluates the incidence, types, and clinical outcomes of venous thromboembolic events (VTEs) in NEN patients. Methods: A systematic search of PubMed, Scopus, and Embase was conducted to identify studies on TEs in NENs. Eligible studies included case reports, case series, and retrospective cohort studies reporting VTEs, including deep vein thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT). Data were extracted on tumor site, functionality, differentiation grade, and VTE type. Results: In total, 33 studies were included, comprising 26 case reports, 2 case series, and 5 retrospective cohort studies. VTE prevalence ranged from 7.5% to 33% across studies. The most common VTEs were DVT, PE, and portal vein thrombosis (PVT). A meta-analysis revealed a pooled VTE prevalence of 11.1% (95% CI: 9.07–13.53%). Pancreatic NENs exhibited the highest thrombotic burden, particularly in poorly differentiated and advanced-stage tumors. Functioning tumors, including glucagonomas and ACTH-secreting NENs, were strongly associated with VTEs, potentially related to their systemic effects on coagulation and inflammation. Conclusions: Venous thromboembolism is a significant complication in NEN patients, especially in advanced or poorly differentiated tumors. Early detection and targeted management are critical for improving outcomes. Further investigations are required to clarify the mechanisms underlying thromboembolism in NENs and to develop optimized prophylactic and therapeutic strategies tailored to this patient population. Full article

Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, is a significant burden on health and economic systems worldwide. Improved VTE management calls for the integration of biomarkers into diagnostic algorithms and scoring systems for risk assessment, possible complications, and mortality. This literature review discusses novel biomarkers with potential diagnostic and prognostic value in personalized VTE management. The pathophysiology of thrombosis starts with cell interactions in the vascular environment and continues with more complex, recently discussed processes such as immunothrombosis and thromboinflammation. Their clinical applicability is in the use of complete blood count (CBC)-derived immuno-inflammatory indices as attractive, readily available biomarkers that reflect pro-thrombotic states. Indices such as the neutrophil-to-lymphocyte ratio (NLR = neutrophil count divided by lymphocyte count), platelet-to-lymphocyte ratio (PLR = platelet count divided by lymphocyte count), and systemic immune-inflammation index (SII = NLR multiplied by platelet count) have demonstrated predictive value for thromboembolic events. Nevertheless, confounding data regarding cutoffs that may be implemented in clinical practice limit their applicability. This literature review aims to investigate neutrophil and platelet interactions as key drivers of immunothrombosis and thromboinflammation while summarizing the relevant research on the corresponding CBC-derived biomarkers, as well as their potential utility in day-to-day clinical practice. Full article

Vitamin D (VD) is a vital lipophilic secosteroid hormone known for its essential role in maintaining skeletal health and regulating calcium and phosphate metabolism. Recent evidence has begun to illuminate its significance beyond bone health, particularly in relation to thrombosis—a condition characterized by blood clot formation within the vascular system that can lead to serious cardiovascular events such as myocardial infarction and stroke. VD deficiency, defined as a plasma 25-hydroxyVD level below 25 nmol/L, affects a substantial portion of the global population, with prevalence rates ranging from 8% to 18%. This study systematically explores the relationships between VD levels and the risk of thrombosis, investigating the underlying mechanisms including VD’s anticoagulant properties, influence on inflammatory pathways, and interactions with endothelial cells. Epidemiological data suggest that low serum levels of VD correlate with an increased risk of venous thromboembolism (VTE), although the reported findings remain inconsistent. Mechanisms that potentially link VD to thrombotic risk include modulation of thrombomodulin and tissue factor expression, as well as enhancement of anti-inflammatory cytokines. Given the prevalence of VD insufficiency, particularly among populations with limited exposure to sunlight, this research highlights the urgent need for strategies to increase VD levels through dietary modifications and supplementation in order to prevent thrombotic events. Full article

Catheter-related thrombosis (CRT) is a frequent and potentially serious complication associated with the widespread use of intravascular devices such as central venous catheters, including peripherally inserted central catheters and implantable port systems, pacemakers or implantable cardioverter-defibrillators. Although CRT management has been informed by guidelines extrapolated from lower extremity deep vein thrombosis (DVT), unique challenges remain due to the distinct anatomical, pathophysiological, and clinical characteristics of upper extremity DVT. Risk factors for CRT are multifactorial, encompassing patient-related characteristics such as cancer, prior venous thromboembolism, and infection, as well as catheter-specific factors like device type, lumens, and insertion site. The diagnosis of CRT relies primarily on ultrasonography; however, computed tomography angiography and magnetic resonance imaging play a complementary role, particularly in anatomically challenging cases or when complications such as pulmonary embolism or superior vena cava syndrome are suspected. Treatment strategies for CRT include anticoagulation, catheter removal when feasible, and, in select cases, local thrombolysis or catheter-directed interventions. Anticoagulation remains the cornerstone of therapy, with direct oral anticoagulants increasingly favored due to their safety profile and efficacy. This article provides a detailed review of CRT, focusing on clinical features, diagnostic methods, and treatment strategies while addressing specific challenges in managing pacemaker and hemodialysis catheter-related thrombosis. Full article