Search Results (731)

Background: End-stage renal disease (ESRD) patients on haemodialysis present a high burden of cardiovascular comorbidities and require anticoagulation, which increases bleeding risk. Methods: We performed a retrospective observational study (2021–2024) in the Haemodialysis Centre of The Clinical Emergency Hospital of Constanta County, Romania, including 50 adults with stage G5 CKD on haemodialysis for ≥3 months and receiving anticoagulant therapy. We collected from electronic medical records detailed demographic data (age, sex, place of residence), comorbidities (hypertension, atrial fibrillation, ischaemic heart disease, diabetes, deep-vein thrombosis, stroke, myocardial infarction, pulmonary embolism, cirrhosis), lifestyle factors (smoking and alcohol consumption), vascular access type (arteriovenous fistula or central venous catheter) and laboratory parameters (haemoglobin, haematocrit, creatinine, albumin, total protein, electrolytes, LDL- and HDL-cholesterol, total cholesterol, INR, APTT, D-dimer, BNP, CK-MB, troponin). All laboratory units were standardised and checked for plausibility. Results: Median age was 71 years; 48% were female. The most common comorbidities were: hypertension (100%), atrial fibrillation (100%) and ischaemic heart disease (62–81%). Patients exhibited severe anaemia (mean Hb ~9.7 g/dL), nephrotic-range proteinuria, hypoalbuminaemia, and impaired coagulation profiles (INR ~1.8–1.9; prolonged APTT in men). Female patients had higher platelet counts and D-dimer levels, suggesting a stronger prothrombotic profile, while males showed longer APTT. Cardiovascular strain was reflected by elevated BNP in men and also troponin/CK-MB. Correlations included smoking with leukocytosis, alcohol with increased urine density, diabetes with higher urea and lower protein, and subtherapeutic INR in cerebrovascular disease. Conclusions: Patients with ESRD on haemodialysis and anticoagulant therapy display a complex interplay of cardiovascular comorbidities, anemia, overlapping thrombotic and bleeding risks, with sex-specific differences. Therefore, systematic monitoring of proteinuria, haemoglobin, D-dimer, and coagulation markers is crucial to balance thrombotic and bleeding risks. Objective: To characterise the clinical and paraclinical profile and comorbidity–laboratory correlations of ESRD patients undergoing haemodialysis and anticoagulant therapy. Full article

Background/Objectives: Thrombosis, a critical condition that can have severe consequences, such as myocardial infarction and cerebral infarction, can be induced by steroid drugs. Although the mechanisms for inducing thrombosis are known for some types of steroid drugs, much remains unknown about the differences in the tendency and mechanisms for thrombosis. Methods: To address this knowledge gap, we analyzed the relationship between thrombosis and steroid use by utilizing the U.S. Food and Drug Administration Adverse Event Reporting System database. From the database, we extracted demographic and drug information and information on reported adverse events from 2004 to 2024. We characterized drugs according to physiological function, receptor specificity, and Anatomic Therapeutic Chemical classification and calculated the proportion of steroid drugs that were likely to induce thrombosis. Results: Among steroid drugs, sex hormones such as androgens, progestogens, and estrogens appeared to have particularly high potential for causing thrombotic events. Results of principal component analysis and cluster analysis indicated that sex hormone preparations were associated with an increased risk of venous thrombosis. In addition, cardiovascular medications and mineralocorticoids, which are used to treat diseases of major organs, showed a tendency to induce large-vessel occlusions. Conclusions: These findings may be useful for selecting steroid drugs for patients who are at risk for similar adverse effects. Full article

Endothelial dysfunction (characterized by reduced vasodilation or vasoconstriction, oxidative stress, inflammation, and pro-thrombotic condition) is a critical factor in the pathophysiology of various cardiovascular conditions, and the application of anesthetics can affect this dysfunction. Patients undergoing major surgery, especially cardiovascular surgery, are at increased risk of endothelial dysfunction. The impact of anesthetics on endothelial function can vary depending on the specific agent, dosage, duration of exposure, comorbidities, etc. Certain anesthetics, especially at higher doses, may increase the production of reactive oxygen species (ROS), leading to oxidative stress and endothelial dysfunction through reduced nitric oxid (NO) availability. Some anesthetics can modulate inflammatory responses, either by suppressing or exacerbating inflammation, or may affect the permeability of the endothelium, potentially leading to pulmonary edema and disruption of the blood-brain barrier. Anesthetics can influence endothelial glycocalyx. Understanding anesthetics effects is crucial for optimizing anesthetic management, particularly in patients with pre-existing cardiovascular issues. Therefore, the aim of this review is to critically evaluate the effects of different classes of anesthetics on endothelial function and oxidative stress. Specifically, we address how anesthetics influence NO bioavailability, endothelial glycocalyx integrity, inflammatory and oxidative pathways, and clinical outcomes in surgical patients. By summarizing current evidence, we aim to highlight mechanistic insights and identify potential perioperative strategies to minimize endothelial dysfunction. Full article

During pregnancy, the maternal hemostatic system undergoes significant changes to support placental angiogenesis, maintain fetal blood flow, and ensure safe delivery. This study investigates the dysregulation of hemostasis in placental insufficiency and explores potential markers for diagnosing and managing this gestational complication. Thromboelastography, coagulation and fibrinolysis functional assays, ELISA, and immunoblotting were employed to assess hemostasis dysregulation in placental dysfunction of two cohorts of pregnant women with placental dysfunction and healthy controls. Thromboelastographic analysis revealed no significant differences in clot lysis indices between the control and placental dysfunction groups, with values remaining within normal ranges, suggesting this method’s limitations for assessing fibrinolysis in pregnancy. The placental dysfunction group demonstrated moderately increased fibrinogen levels and platelet sensitivity to ADP, indicating hemostasis reactiveness. Significantly lower D-dimer levels, decreased plasminogen activator inhibitor activity (total PAI-1 + PAI-2), and increased plasminogen activator activity, driven primarily by uPA in the placental dysfunction group, indicated abnormal fibrinolysis. Immunoblotting confirmed elevated uPA/uPA-PAI complexes and reduced tPA/tPA-PAI complexes, indicating that shutdown of tPA-mediated fibrinolysis and induction of uPA-driven vessel-wall-associated proteolysis are linked to placental dysfunction. Placental dysfunction involves fibrinolytic system dysregulation, marked by decreased PAI and tPA, uPA overproduction, and hypofibrinolysis, contributing to thrombotic risks, impaired placental flow, and complications like fetal growth retardation. PAI/PA ratio and D-dimer levels have diagnostic potential for placental-dysfunction-associated complications. Full article

Background: Legg–Calvé–Perthes disease (LCPD) is a rare avascular osteonecrosis of the proximal femoral epiphysis and typically occurs during the childhood growth phase. LCPD is a complex illness of unknown origin, which is considered the main difficulty in the study of this disease. Various theories on LCPD etiology have been proposed; however, no consensus has been reached about its origin. Our research objective was to evaluate the polymorphisms FVL rs6025, FVIII rs5987061, FIX Malmö rs6048, PAI-1 rs1799889, eNOS rs17899983/rs2070744, IL-23R rs1569922/rs154655686/7539625, and TNF-α rs180062, and their relationship with LCPD. Methods: A blood sample was taken from each study participant. Complete blood count, coagulation times and factors, antithrombotic proteins, and homocysteine (Hcy) were determined using a coagulometric method. DNA was obtained and genotyped using real-time PCR with TaqMan probes. Genotypic and allelic distributions were analyzed using comparative analysis, the Hardy–Weinberg equilibrium, and OR. Results: This study included 46 children: 23 with LCPD (cases) and 23 without (controls). Statistically significant differences were found in Prothrombin Time, Factor V, and Factor IX activity, as well as Hcy concentration; these values suggest the presence of hypercoagulable states in patients, which can cause thrombotic events. On the other hand, significant differences were also found in the neutrophil–lymphocyte ratio and systemic immune-inflammation index, showing major inflammation states in the patient group. Moreover, statistically significant differences were found in the IL-23R rs1569922 polymorphism; it was found that carriers of the T/T and C/T genotypes have an increased risk of developing LCPD. Conclusions: Our results show greater hemostatic activity and inflammation in the group of patients included in this study, supporting various theories previously proposed. Therefore, we believe that LCPD is a multifactorial condition in which hemostatic, inflammatory, and genetic factors play a central and triggering role in the disease. Full article

A 75-year-old Jehovah’s Witness with recent ST-elevation myocardial infarction (STEMI) underwent percutaneous coronary intervention (PCI) with stenting of the proximal LAD. She was later diagnosed with gallbladder cancer and required urgent surgery but firmly refused allogeneic blood transfusion. This posed a major challenge, as the surgery was expected to cause significant bleeding, and the patient had undergone coronary stenting within the previous three months, which is when the risk of stent thrombosis is highest if dual antiplatelet therapy (DAPT) is interrupted. After conducting a careful multidisciplinary discussion and obtaining informed consent, both aspirin and clopidogrel were discontinued five days preoperatively. Through comprehensive blood conservation strategies—including acute normovolemic hemodilution (ANH), intraoperative cell salvage, and robotic-assisted minimally invasive surgery—the patient successfully underwent extended cholecystectomy without transfusion. This case highlights the possibility of safe, completely transfusion-free major surgery in patients with recent PCI and high thrombotic risk when individualized perioperative planning is applied. Full article

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, poses a substantial risk for venous thromboembolism (VTE). Managing CML in patients with such prothrombotic predispositions presents complex therapeutic challenges, particularly in selecting an appropriate TKI and managing anticoagulation. Case Presentation: A 33-year-old woman with congenital thrombophilia (type I protein S deficiency and heterozygous Factor V Leiden mutation) and a history of VTE on long-term anticoagulation with acenocoumarol presented with CML. She exhibited primary resistance to first-line imatinib and poor tolerance with suboptimal response to second-line bosutinib. Third-line treatment with asciminib led to a rapid and sustained major molecular response (MR4.5) without bleeding or thrombotic complications. Conclusions: This case highlights the importance of individualized, multidisciplinary management in CML patients with coexisting thrombophilia. Asciminib, with its favorable cardiovascular safety profile, represents a promising therapeutic option in high-risk patients where other TKIs may be contraindicated due to resistance, intolerance, or thrombotic risk. Full article

Apolipoprotein C3 (apoC3) is a key regulator of triglyceride metabolism and has emerged as a potential therapeutic target for reducing the risk of cardiovascular disease. However, its broader physiological functions are not fully understood. This study investigates the role of apoC3 in platelet function and thrombus formation. Interestingly, human apoC3 was found to rapidly inhibit platelet activation over the tested concentration range of 0.1–10 µg/mL, with significant effects observed at low concentrations and brief pre-incubation times (from 1 min). At a concentration of 10 µg/mL, apoC3 suppressed platelet activation by approximately 70% in response to ADP and by approximately 40% in response to collagen stimulation. Depleting apoC3 from human serum enhanced platelet aggregation by more than 25 % (1.28 ± 0.19 vs. vehicle), indicating an endogenous regulatory function of apoC3. Mechanistically, apoC3 binding to platelets reduced both GPIIb/IIIa activation and P-selectin expression by around 20%. ApoC3 binding to platelets increased when platelets were activated by ADP and was partially mediated by GPIIb/IIIa, implicating this integrin as a functionally relevant receptor. Taken together, these findings reveal a novel link between apoC3 and platelet biology with potential implications for thrombotic risk and vascular homeostasis. Full article

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal hematologic disorder caused by somatic mutations in the PIGA gene of hematopoietic stem cells, leading to the absence of GPI-anchored proteins, including the complement regulators CD55 and CD59. This deficiency results in uncontrolled complement activation, causing intravascular and extravascular hemolysis, thrombosis, and bone marrow failure. Historically associated with substantial morbidity, PNH management has been transformed by the advent of complement inhibitors. Eculizumab, the first approved C5 inhibitor, significantly reduced thrombotic risk and improved survival but did not eliminate anemia due to extravascular hemolysis. Newer agents now target proximal complement components, offering broader control and improved convenience. This review summarizes the pathophysiology of PNH, evaluates established and emerging complement inhibitors, and discusses ongoing therapeutic challenges and future directions. Full article

Thrombotic complications are a common cause of morbidity and mortality in cancer patients. Factor XI (FXI) appears to play a direct role not only in thrombotic pathogenesis but also in cancer progression. This comprehensive review aims to define the pathophysiological relationships between FXI and cancer and to assess existing therapeutic opportunities targeting this factor. This review highlights how FXI is implicated in tumor growth, tumor cell adhesion and migration, inflammation, and angiogenesis. FXI inhibition has been shown to reduce the risk of thrombosis, with a potentially improved safety profile in terms of bleeding risk. Several molecules, such as asundexian and abelacimab, are in clinical trials for the prevention and treatment of venous thromboembolic events, catheter-related thrombosis, and arterial thromboembolic events in cancer patients. In conclusion, factor XI is closely linked to the pathogenesis of cancer and its thromboembolic complications. The use of FXI inhibitors emerges as a promising therapeutic strategy, offering potentially positive effects in the prevention and treatment of thromboembolic complications without significantly increasing the risk of bleeding, a limitation of conventional anticoagulants. The preliminary evidence is that further clinical trials are required and that the available data is not enough to make firm clinical recommendations. Full article

In patients on oral anticoagulation (OAC), typically for atrial fibrillation (AF), undergoing percutaneous coronary intervention (PCI), the antiplatelet drugs to be added to direct oral anticoagulant (DOAC) are aspirin and clopidogrel during the initial, short (up to one week) period of triple antithrombotic therapy (TAT), and clopidogrel alone during the subsequent 6- to 12-month period of double antithrombotic therapy (DAT). Both direct and indirect data support the recommendation to avoid the more potent P2Y12 inhibitors—ticagrelor and prasugrel—as part of TAT, owing to the increased risk of bleeding. There is less and inconclusive data available regarding the safety and efficacy of DAT when ticagrelor or prasugrel are used instead of clopidogrel. Also, there is very limited evidence for the use of aspirin instead of clopidogrel in a DAT regimen. While acknowledging the safety and effectiveness of the recommended strategies above, it would, nonetheless, be valuable to have alternative options in the choice of antiplatelet agents. In case of very high thrombotic risk, especially when stents are positioned in potentially risky sites (such as the left main or last remaining vessel) a more potent P2Y12 inhibitor than clopidogrel may be warranted. Moreover, non-responsiveness to, or pharmacological interactions of, clopidogrel may hamper its efficacy. In this review, we aim at presenting and discussing the evidence supporting the current recommendations for the use of the various antiplatelet agents in AF patients on OAC undergoing PCI, as well as at giving a glimpse at future perspectives. Full article

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide, arising from complex interactions among metabolic, genetic, and environmental factors. Nicotinamide N-methyltransferase (NNMT) has recently emerged as a key metabolic regulator in CVD pathogenesis. By consuming nicotinamide and methyl groups, NNMT perturbs epigenetic, metabolic, and redox pathways that are critical for cardiovascular health. NNMT-mediated NAD⁺ depletion impairs mitochondrial function, sirtuin (SIRT) activity, redox balance, and energy metabolism, thereby creating a pro-atherogenic environment. NNMT and its product 1-methylnicotinamide (1-MNA) show a complex duality: they modulate SIRT activity—particularly SIRT1 and SIRT3—to influence gluconeogenesis, cholesterol synthesis, lipogenesis, and mitochondrial antioxidant defenses. NNMT upregulation also elevates homocysteine levels, activating pro-inflammatory and pro-oxidative cascades (e.g., TLR4–NF-κB and STAT3–IL-1β). Growing evidence links NNMT to major CVD risk factors, including hyperlipidemia, hypertension, diabetes mellitus, and obesity. Thus, NNMT has a multifaceted role in cardiovascular health: while its enzymatic activity is often pathogenic (via NAD⁺/SAM consumption and homocysteine production), its metabolite 1-MNA can exert protective effects (via NRF2 activation and anti-thrombotic mechanisms). This duality highlights the need to delineate the molecular processes that balance these opposing actions. Experimental studies using small-molecule NNMT inhibitors and RNA interference have shown promising cardiometabolic benefits in preclinical models, including improved insulin sensitivity, reduced atherosclerosis, and attenuated cardiac dysfunction. However, no clinical trials have yet targeted NNMT specifically in CVD. Future research should clarify the tissue-specific functions of NNMT and translate these insights into novel therapeutic strategies. Full article

Background: Elective surgery soon after SARS-CoV-2 infection is linked to high morbidity, but the risk > 7 weeks post-infection is uncertain. Methods: A PROSPERO-registered systematic review (CRD42023416842) following PRISMA 2020 searched PubMed, Web of Science, WHO COVID Database, Wiley, Google Scholar, and Scopus (Jane 2020–July 2025) for studies reporting postoperative outcomes in patients with confirmed COVID-19 ≥ 7 weeks before elective surgery. Primary endpoints were cardiopulmonary, neurological, renal and thrombotic complications, ICU/hospital stay and 30-day mortality. Results: Thirteen observational studies (38,055 patients) met inclusion criteria. In patients operated ≥7 weeks after mild or asymptomatic infection, overall mortality rate was 2.27% (607/26,688), with no significant excess versus uninfected controls. Pneumonia (1.66%), pulmonary embolism (1.47%), arrhythmias (2.57%) and myocardial injury (1.06%)—did not exceed baseline surgical rates. Thrombosis occurred in 2.8% but lacked a clear association with prior infection. Conversely, individuals with previous moderate-to-severe disease or recent COVID-19-related hospitalization showed higher complication rates, especially in complex procedures such as coronary bypass. Conclusions: Evidence to date indicates that COVID-19 history beyond seven weeks does not independently raise perioperative morbidity or mortality for most elective procedures. Full article

Background: Sickle cell disease (SCD) is among the most prevalent inherited hemoglobinopathies and is strongly associated with numerous coagulation abnormalities, hence constituting a severe hypercoagulable state. Methods: We conducted a single-center retrospective observational study of patients with SCD who were monitored at Hippokration Hospital of Thessaloniki between 1999 and 2024. Demographic characteristics, hemoglobin (Hb) genotype, medical history, anticoagulant and antiplatelet therapy, dosage of anticoagulant treatment, recurrence of the first episode of venous thromboembolism (VTE) and relevant laboratory values were examined as possible risk factors. Results: Among 46 patients, 12 (26.1%) developed thrombosis with the majority (75%) carrying the HbS/β-thal genotype. The prevalence of VTE in this study was 17.4%. Variables significantly associated with an increased risk of thrombosis included age at the time of thrombosis, patient age, use of anticoagulant treatment, anticoagulant dosage, antiplatelet therapy and type of transfusion (p < 0.05). On multivariate analysis, anticoagulant treatment and its dosage retained statistical significance (p < 0.05). Conclusions: These findings reinforce the strong association between SCD and thrombotic events. Despite the availability of a broad therapeutic armamentarium and increasing knowledge of the underlying disease mechanisms, the prevention and management of thrombosis in these patients remains a challenge. Full article

Introduction: Patients with inflammatory bowel disease (IBD) are at increased risk of developing other autoimmune disorders due to possible shared genetic, environmental, and immunological mechanisms. While autoimmune diseases are frequently observed in patients with IBD, data quantifying their inpatient prevalence and their association with outcomes such as mortality remain limited. Methods: National Inpatient Sample (NIS) 2016–2020 and International Classification of Diseases 10th Version, Clinical Modification (ICD-10-CM) diagnosis codes were used to identify patients with IBD and autoimmune conditions. A multivariate logistic regression analysis to identify an association between various autoimmune diseases and various IBDs was performed. Results: The study population included 141,478,025 patients. An association was found between 24 autoimmune conditions and IBD. Conclusions: Our study identified autoimmune comorbidities that are more prevalent in IBD patients. We found that polymyositis, AIHA, ITP, and thrombotic microangiopathy are associated with a higher risk of in-hospital mortality. Psoriasis and hypothyroidism are associated with a lower risk of in-hospital mortality. Further studies are needed to explore the mechanisms responsible. Full article