Search Results (602)

Background: Circulating microRNAs (miRNAs) have emerged as potential biomarkers of platelet reactivity and thrombotic risk. Among them, miR-223-3p regulates P2Y12 receptor expression and may influence response to antiplatelet therapy. This study aimed to evaluate the prognostic value of selected circulating miRNAs in post-stroke patients receiving antiplatelet treatment. Methods: Sixty ischemic stroke survivors were prospectively enrolled and followed for 18 months for recurrent vascular events (stroke, transient ischemic attack, or myocardial infarction). Plasma levels of miR-126-3p, miR-223-3p, miR-24-3p, and miR-199a-5p were quantified using reverse transcription real-time PCR. Clinical data, antiplatelet regimen, statin use, and Essen Stroke Risk Scores (ESRS) were recorded. Logistic regression was applied to identify independent predictors of thrombotic events. Results: Expression of all examined miRNAs differed significantly across treatment groups. The dual antiplatelet therapy (DAPT) group showed the highest levels of miR-126-3p and miR-199a-5p (p < 0.01). Within the statin-naïve DAPT subgroup, lower miR-199a-5p levels (p < 0.001) were observed among patients who experienced ischemic events (n = 7/60; 12%; stroke = 4, TIA = 2, ACS = 1) during 18 months of follow-up. In multivariate analysis, reduced miR-223-3p remained the only independent predictor of recurrent thrombotic events (OR 1.18, 95% CI 1.01–1.37, p = 0.036), independent of ESRS and platelet reactivity. Elevated miR-126-3p and miR-199a-5p were associated with favorable treatment response, particularly among statin users. Conclusions: This study identifies low circulating miR-223-3p as an independent biomarker of thrombotic risk in post-stroke patients, potentially reflecting enhanced platelet activation via P2Y12 signaling. In contrast, higher miR-126-3p and miR-199a-5p levels may indicate more effective antiplatelet response. These findings support the potential utility of miRNA profiling for individualized antiplatelet therapy and long-term risk stratification after ischemic stroke. Full article

Background/Objectives: Prevention and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major clinical issue in hospitalized patients. Some aspects of VTE management lack clarity due to differing physicians’ opinions and behaviors. Methods: A multidisciplinary steering committee identified two main areas of uncertainty: VTE prophylaxis and PE management in special settings. A multiple-choice questionnaire including 10 statements was circulated to 183 doctors trained in VTE management. The expected benefit-to-harm ratio was represented on a nine-point Likert scale, with consensus (≥75% agreement) on scores of 1–3 indicating inappropriate and 7–9 indicating appropriate care measures. Results: In online voting, a consensus was reached for 9/10 statements. Respondents considered the following to be appropriate: risk assessment of VTE (93.44%) and bleeding (91.6%) in hospitalized medical patients; low-molecular weight heparin (LMWH) prophylaxis for inpatients with pneumonia and malignancy (82.78%); therapeutic doses of LMWH/fondaparinux in patients with intermediate/high risk of PE with (80.9%) or without (77.97%) instability criteria; and echocardiography to manage patients with a post-PE syndrome (93.99%). Respondents considered the following to be inappropriate: use of 4000 IU LMWH in chronic renal failure (80.46%); use of 2000 IU LMWH in persons on dual antiplatelet therapy (77.01%); and use of low-dose apixaban (2.5 mg) in pregnancy (88.57%) or in subsegmental PE with hypoxemia (82.46%). No consensus was reached on the identification of PE cases eligible for outpatient treatment. Conclusions: Our findings show persistent gaps between guideline recommendations and clinical implementation despite improved awareness among physicians. Uncertainty persists regarding criteria for outpatient PE eligibility and/or for validation of bleeding-risk models. Full article

Although COVID-19 is associated with significant thrombo-inflammatory complications, reliable biomarkers to guide antithrombotic therapy remain limited. Immature platelet fraction (IPF) reflects platelet turnover and may indicate heightened thrombotic risk. We retrospectively analyzed 133 hospitalized COVID-19 patients (median age 68 years) at a single center. IPF and inflammatory markers (WBC, ANC, D-dimer, LDH, CRP) were measured on admission. Correlations between IPF and these biomarkers were assessed overall and in clinical subgroups (age, sex, disease severity, comorbidities, and treatment). We found that IPF was positively correlated with WBC and ANC in patients less than 70 years old (r = 0.36 and 0.33, respectively; p < 0.05), males, and those with moderate-to-severe disease. Among patients with congestive heart failure, IPF correlated strongly with D-dimer (r = 0.78, p = 0.013). Similar associations were observed in patients requiring enoxaparin or antiplatelet therapy. No significant correlations were found in patients age 70 or older. Based on these findings, we conclude that elevated IPF is associated with increased inflammatory and thrombotic activity in hospitalized COVID-19 patients, especially in younger, male, and more severe cases. These findings suggest IPF may serve as a dynamic marker for thrombo-inflammation and help identify patients who might benefit from more intensive antithrombotic therapy. Larger studies are warranted to validate IPF as a biomarker for personalized management of COVID-19. Full article

(1) Background: Whether anticoagulation can be resumed in atrial fibrillation (AF) combined with intracranial hemorrhage (ICH), and which anticoagulation modality is used with better efficacy and safety, is unknown. (2) Method: Randomized controlled trials (RCTs) and observational studies on relevant topics were included by searching five databases: PubMed, EMBASE, EBSCO, Cochrane Central Register of Controlled Trial and ClinicalTrials. Bayesian network meta-analysis was performed to analyze the effect of oral anticoagulant (OAC), new oral anticoagulant (NOAC), warfarin, antiplatelet, left atrial appendage occlusion (LAAO) and no therapy in patients with AF after intracranial hemorrhage. (3) Results: We included 16 studies involving 25,483 patients. Compared with no antithrombotic therapy, the risk of thromboembolism and all-cause mortality were both reduced with OAC (OR: 0.38, 95% CI: 0.21–0.67; OR: 0.45, 95% CI: 0.25–0.8) and LAAO (OR: 0.11, 95% CI: 0.01–0.76; OR: 0.11, 95% CI: 0.01–0.88), and there was no increased risk of recurrent intracranial hemorrhage. Regarding thromboembolism, OAC (OR: 0.28, 95% CI: 0.11–0.69) was superior to antiplatelet therapy, and antiplatelet therapy (OR: 12.59, 95% CI: 1.57–133.50) was associated with a higher risk of thromboembolism than LAAO. There were no significant differences in recurrent intracranial hemorrhage between the interventions. LAAO appeared to be the best option for reducing thromboembolism (SUCRA: 0.96), recurrent intracranial hemorrhage (SUCRA: 0.75) and all-cause mortality (SUCRA: 0.94). (4) Conclusions: Based on this network meta-analysis, we hypothesize that LAAO has the highest likelihood of reducing the risk of thromboembolism and recurrent intracranial hemorrhage, as well as all-cause mortality in patients with AF after intracranial hemorrhage, followed by OAC. 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: Large-volume paracentesis (LVP) of the peritoneal and pleural cavities is a common diagnostic and therapeutic intervention in patients with liver cirrhosis or advanced heart failure, which are both frequently associated with ascites or pleural effusion. Although generally regarded as a low-risk procedure, LVP may lead to complications such as intrapleural or intra-abdominal hemorrhage, and more commonly abdominal wall bleeding, as well as organ puncture and infection. Performing LVP in patients with coagulopathy or bleeding disorders, whether disease-related or due to anticoagulant therapy, poses a significant clinical challenge. The safety thresholds for such procedures remain inconsistent, and strategies to mitigate bleeding risk are still debated among professional societies. Methods: This review integrates institutional experience with a systematic synthesis of the current international literature to identify the safest and most effective approaches for performing LVP in patients with coagulopathy. The methodological framework included a comparative analysis of existing professional guidelines, as well as a critical evaluation of published evidence regarding risk stratification, pre-procedural correction strategies, and peri-procedural management. The evidence grading was assessed with the STAIR checklist. Results: Analysis of the evidence revealed substantial variability among professional recommendations concerning acceptable platelet and INR thresholds, as well as differing approaches to the management of patients receiving anticoagulant or antiplatelet therapy. Despite these discrepancies, the aggregated data support the conclusion that LVP can be performed safely in most patients with mild-to-moderate coagulopathy, provided that appropriate risk assessment and technical precautions are implemented. Conclusions: The resulting evidence-informed suggestions provide a practical framework for clinicians performing LVP in high-risk patients. By emphasizing systematic pre-procedural evaluation, individualized management of coagulopathy, and adherence to standardized procedural techniques, this work aims to promote safety, consistency, and confidence in the performance of large-volume paracentesis across diverse clinical settings. Full article

Background/Objectives: Complex aneurysms of the posterior inferior cerebellar artery (PICA) remain challenging because of their deep location, variable morphology, and proximity to critical neurovascular structures. Although endovascular therapy is preferred, its feasibility is limited in wide-necked, fusiform, or dissecting lesions. We describe our tertiary referral hospital single-center experience with tailored microsurgical and endovascular strategies—emphasizing occipital artery–PICA (OA-PICA) bypass, transcondylar fossa craniotomy, and cerebellomedullary fissure opening—and analyze perioperative factors that influence outcome. Methods: All consecutive patients treated for PICA origin or distal-PICA aneurysms between January 2021 and April 2025 were retrospectively reviewed. Demographics, aneurysm characteristics, procedure type, antithrombotic regimen, complications, diffusion-weighted MRI findings, and 3-month modified Rankin Scale scores were collected. Results: Twelve aneurysms (mean age 61.4 ± 15.2 years; 8 women) were treated: trapping + OA-PICA bypass in 5, direct clipping in 2, flow diverter in 1, endovascular parent artery occlusion in 2, coil embolization in 1, and a hybrid bypass-plus-coil strategy in 1. Two cases were ruptured aneurysms. Perioperative aspirin was used in 2/5 bypass cases; heparin was added in one hybrid case. Asymptomatic PICA-territory infarcts occurred in the three bypasses performed without antiplatelet therapy (one with intra-anastomotic thrombus). No leaks or subcutaneous collections of cerebrospinal fluid were encountered, and no graft occlusions were observed. At 3 months, 9/12 patients achieved a good outcome (mRS 0–2); among them, only one patient with subarachnoid hemorrhage (SAH) experienced postoperative worsening of the mRS. Two cranial nerve palsies (one permanent, one transient) and one wound site hematoma (heparin-associated) resolved without sequelae. Conclusions: Meticulous operative planning allows safe treatment of complex PICA aneurysms. Perioperative aspirin appears beneficial for OA-PICA bypass, whereas perioperative heparin increases bleeding risk. Individualized selection of endovascular, microsurgical, or combined strategies yields favorable early neurological outcomes in this demanding subset of cerebrovascular disease. Full article

Transcatheter aortic valve implantation is rapidly emerging as the leading treatment for severe aortic valve stenosis, especially in elderly and high-risk or inoperable patients. Prosthetic embolism is a rare but serious complication of transcatheter aortic valve replacement. Patients who develop prosthetic embolism are at increased risk of mortality and morbidity. These include stroke and aortic dissection associated with manipulation of the prosthesis in the ascending aorta. Treatment of valve embolisms into the aorta may differ depending on the type of valve; however, it traditionally relies on repositioning the valve to an appropriate position. To date, there are no established pharmaceutical guidelines for the management of patients with valve prosthesis embolization. We present a case report of the implantation of a second aortic valve prosthesis after periprocedural embolization of the first transcatheter valve, resulting in residual floating in the ascending aorta and following treatment with oral anticoagulation as well as single antiplatelet therapy due to the increased risk of thrombogenesis. This case report provides an example of the management of a transcatheter valve embolization with residual floating and highlights the need for further studies to address this issue. Full article

Background: Dual antiplatelet therapy (DAPT), combining aspirin with a P2Y12 receptor inhibitor (P2Y12i), remains central to the management of acute myocardial infarction (MI), especially in patients undergoing percutaneous coronary intervention (PCI). However, the pharmacodynamic response to antiplatelet therapy may vary with body composition. This study investigates the association between body mass index (BMI) and clinical outcomes in MI patients treated with PCI and DAPT. Methods: This retrospective cohort study analyzed data from 52,119 MI patients treated with coronary stenting from 2014 to 2021, sourced from the Hungarian Myocardial Infarction Registry. Patients were stratified into clopidogrel-based (n = 44,480) and potent P2Y12i-based (prasugrel or ticagrelor; n = 7639) DAPT cohorts. Clinical outcomes—including 12-month mortality and ischemic events—were assessed across BMI categories. Kaplan–Meier analysis and LASSO Cox regression identified predictors of mortality, while decision curve analysis (DCA) evaluated the net clinical benefit of potent P2Y12i across BMI strata. Results: Univariate and multivariate Cox regression analyses identified BMI and potent P2Y12i treatment as significant predictors of 365-day mortality, with higher BMI associated with lower observed rates of mortality, major adverse cardiovascular events (MACEs), and stroke. However, higher BMI was also associated with an increased risk of repeat revascularization and PCI. This study found that the protective effect of potent P2Y12i treatment was consistent across different BMI categories. Conclusions: In patients with MI undergoing PCI, elevated BMI was paradoxically associated with more favorable short-term outcomes, including reduced mortality. Potent P2Y12i therapy demonstrated a consistent benefit across BMI categories, supporting its broad application irrespective of body mass. Full article

Background/Objectives: Clopidogrel is a P2Y₁₂ receptor inhibitor commonly used as antiplatelet therapy for patients with cardiovascular occlusive diseases. However, its role in vascular remodeling remains poorly understood. Platelets orchestrate the sterile inflammation in arteriogenesis, an endogenous process to bypass an occluded artery. Therefore, we investigated the impact of P2Y₁₂-inhibition by Clopidogrel on arteriogenesis. Methods: In this study, we utilized a well-established murine hindlimb model of arteriogenesis. To quantify the growth of collateral arteries, we employed laser-Doppler perfusion measurements and immunohistological analysis of growing compared to resting collateral arteries. Additional immunofluorescence and histological stains were conducted to assess immune cell recruitment and activation. Whole-blood flow cytometry was performed to analyze platelet–leukocyte interactions, and complete blood counts were obtained to quantify leukocyte and platelet numbers. Results: The findings of this study demonstrate that Clopidogrel promotes perfusion recovery following the induction of arteriogenesis compared to controls, attributed to elevated levels of proliferating vascular cells. Furthermore, compared to controls, Clopidogrel treatment significantly enhanced platelet-leukocyte interactions, increasing perivascular mast cell recruitment and degranulation, finally resulting in regenerative macrophage accumulation required for collateral artery growth. Conclusions: Clopidogrel treatment boosts arteriogenesis by enhancing the local regenerative inflammation relevant for vascular cell proliferation. Therefore, P2Y₁₂ inhibition may represent a therapeutic option to effectively promote natural bypass growth in patients with cardiovascular occlusive diseases. Full article

Background: Peripheral Artery Disease (PAD) of the lower extremities is a prevalent manifestation of atherosclerotic disease, significantly affecting individuals aged 55–70, with a global incidence of 4–12%. Major risk factors include smoking, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease, all contributing to endothelial damage and subsequent plaque progression. This retrospective study examines the outcomes of endovascular treatment for TASC C and D lesions, which are complex cases that have historically required surgical intervention. Methods: From June 2022 to September 2023, 48 patients were analyzed, with a mean age of 67.48 years; 37.5% were female. Statins were administered to 64.6% of patients, and 93.8% received antiplatelet therapy. Endovascular procedures included balloon angioplasty, stenting, and the use of drug-eluting balloons (DEB), employing varying access routes, primarily via percutaneous approaches. Results: The study revealed a 12-month primary patency rate of 75.8% and a secondary patency rate of 95.5%, highlighting the effectiveness of follow-up interventions. Complications occurred in 10.4% of cases, with a perioperative mortality rate of 0%. Notably, 29.2% of patients required amputation, reflecting the severity of PAD. Conclusions: The outcomes demonstrate that endovascular treatment may be a viable alternative for managing TASC C and D lesions, offering satisfactory clinical outcomes and an acceptable safety profile. Continuous monitoring and interdisciplinary evaluations are essential for optimizing patient care and minimizing complications. As endovascular technologies advance, their role in treating severe peripheral arterial disease is likely to expand. 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

Background: Coronary artery bypass grafting (CABG) remains a standard revascularization strategy for patients with advanced coronary artery disease (CAD). However, a considerable proportion of patients experience recurrent ischemia requiring repeat revascularization. Residual platelet reactivity (RPR) and dyslipidemia are recognized as key factors contributing to graft failure and disease progression. Methods: This observational study was conducted at a tertiary cardiology center in Kazakhstan. A total of 195 post-CABG patients who underwent repeat coronary angiography between 2023 and 2024 recruitment period for recurrent ischemic symptoms within 6–36 months after surgery were included. Clinical characteristics, comorbidities, lipid profiles, and antiplatelet response were analyzed. RPR was measured using the VerifyNow P2Y12 assay when available. Dyslipidemia was defined according to the 2019 and 2021 European guidelines. Results: Elevated RPR was identified in 45% of patients (n = 90) despite dual antiplatelet therapy (p < 0.01). Poor lipid control was frequent among those who underwent repeat percutaneous coronary intervention (PCI), particularly elevated levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (p < 0.05). Both elevated RPR and dyslipidemia were independently associated with native coronary disease progression and graft failure (RPR: OR = 2.8; 95% CI 1.4–5.6; p = 0.003; dyslipidemia: OR = 2.2; 95% CI 1.1–4.3; p = 0.02). The use of ezetimibe was independently associated with a significantly lower risk of repeat stenting (OR = 0.12; 95% CI 0.02–0.75; p = 0.023). Smokers were younger, had lower blood pressure, and less frequently presented with diabetes or chronic kidney disease, demonstrating a pattern consistent with the “smoker’s paradox.” Conclusions: Residual platelet reactivity and dyslipidemia are common and clinically relevant predictors of repeat revascularization after CABG. Optimization of antiplatelet and lipid-lowering therapy should be prioritized in secondary prevention for this high-risk population. These findings are particularly important in Kazakhstan, where post-CABG management strategies warrant further improvement. Full article

In Diabetes Mellitus (DM), a metabolic disorder characterized by elevated blood glucose due to impaired insulin action, platelet function is dysregulated and contributes to the pathological progression of the disease. In type 2 diabetes mellitus (T2DM), hyperglycemia, insulin resistance, oxidative stress, and inflammation impair endothelial function and platelet regulation, promoting a prothrombotic state. Platelet hyperreactivity is associated with T2DM cardiovascular complications, a leading cause of mortality in patients. Antiplatelet therapies often prove ineffective for a subset of T2DM patients due to aspirin resistance, necessitating alternative therapeutic strategies. Resveratrol, a natural polyphenol, is a potential therapeutic agent for T2DM, including inhibition of platelet aggregation. One of the pleiotropic actions of resveratrol is to modulate the F_oF₁-ATP synthase rotational catalysis. Platelet chemical energy demand during the activation phase is achieved through oxidative phosphorylation. Both mitochondrial and extra-mitochondrial oxidative phosphorylation drive aerobic energy production in activated platelets, utilizing fatty acids and glucose, respectively. Hyperglycemia can cause an overwork of the oxidative phosphorylation, producing oxidative stress. Targeting F_oF₁-ATP synthase with resveratrol may reduce platelet hyperreactivity in aspirin-resistant cases. This paper reviews the implications of resveratrol ability to inhibit platelet F_oF₁-ATP synthase on its potential as a novel alternative or synergistic antiplatelet strategy for aspirin-resistant T2DM patients. Full article

Background: Persistent pulmonary hypertension of the newborn (PPHN) remains a life-threatening condition resulting from failure of postnatal circulatory adaptation. Inhaled nitric oxide (iNO) is the standard first-line therapy; however, limited access or inadequate response highlight the need for alternative treatments. Milrinone, a selective phosphodiesterase-3 inhibitor with nitric oxide-independent vasodilatory and inotropic properties, has been proposed as one such option. Methods: In this study we present a case series of three neonates with PPHN—term (41 weeks), late preterm (35 weeks), and extremely preterm (23 weeks)—treated with intravenous milrinone in a neonatal unit without immediate access to iNO. A narrative literature review was also conducted, focusing on clinical outcomes, safety, and therapeutic applicability. Results: Milrinone was initiated within the first 24 h of life. In the term and late-preterm infants, oxygenation and echocardiographic parameters improved within 48 h, with normalization of shunt direction and successful extubation by days 4–10. Transient systemic hypotension occurred in both cases and required dose adjustment or vasoactive support. In the extremely preterm neonate, only temporary hemodynamic improvement was achieved, followed by severe intraventricular hemorrhage and coagulopathy, possibly exacerbated by vasodilatory and antiplatelet effects of milrinone. Conclusions: Milrinone may serve as a feasible adjunct or bridging therapy for PPHN when iNO is unavailable. However, its use requires careful hemodynamic and neurological monitoring, particularly in very preterm infants. Further studies are needed to confirm safety and define optimal dosing across gestational ages. Full article