Search Results (135)

Fibrinolysis assessment is critical for diagnosing and managing clinical blood disorders. Currently available viscoelastic testing platforms provide an overview of global coagulation and fibrinolysis profiles but lack fibrinolysis specific assessment of a preformed clot substrate. The lack of a sensitive, standardized testing platform for fibrinolysis assessment can limit risk stratification and the management of blood disorders. We describe herein the plasma annular clot lysis assay. The assay adapts the previously standardized FITC-tagged fibrin annular clot assay to plasma obtained from healthy human donors. Plasmin at concentrations ranging from 200–800 nM was used as a direct thrombolytic to assess fibrinolysis in plasma-derived annular clots. The Maximum Fibrinolysis Rate (V_MFR), FLU200, T90, and MaxFLU were calculated via tracking of the clot digestion curve over time. V_MFR was correlated with plasma thromboelastography (TEG) parameters to compare with the global viscoelastic testing system. Additionally, plasma annular clot digestion was monitored in the presence of pentamidine to assess drug-specific effects on fibrinolysis tracking. Plasma annular clots linearly tracked fibrinolysis with increasing plasmin concentration. V_MFR across multiple tested plasmin concentrations showed a moderate to strong negative correlation (0.58–0.74) with the observed maximum amplitude from plasma TEG. In the presence of pentamidine (75 µM), the assay was sensitive to identifying differences in the V_MFR across treatment groups. Plasma annular clots provide a platform for fibrinolysis evaluation using a patient’s own plasma to assess therapeutic dosing clinically in addition to testing novel therapeutics preclinically to further understand mechanistic aspects of fibrinolysis. Full article

Cancer-associated thrombosis (CAT) is a leading cause of morbidity and mortality in patients with malignancy, yet its imaging manifestations extend far beyond the conventional diagnosis of deep vein thrombosis and pulmonary embolism. This comprehensive review examines the full spectrum of CAT as encountered by radiologists, from routine venous thromboembolism to unusual-site thromboses, arterial thromboembolic events, catheter-related complications, and endovascular management strategies. Patients with cancer face a four- to seven-fold increased risk of venous thromboembolism compared with the general population, and arterial thromboembolism occurs at more than twice the expected rate, particularly within the first six months following cancer diagnosis. The radiologist’s role spans detection, characterization, and therapeutic guidance across multiple vascular territories. Key diagnostic challenges addressed include the distinction between bland and tumor thrombus—a determination with direct implications for TNM staging, surgical planning, and systemic therapy selection—and the recognition of incidental thromboembolism, which carries prognostic weight equivalent to symptomatic events and warrants similar clinical management. Emerging applications of diffusion-weighted MRI, contrast-enhanced ultrasound, and FDG-PET/CT provide a multiparametric toolkit for thrombus characterization, while artificial intelligence and machine learning show promise for improving patient selection and reducing unnecessary imaging. The expanding recognition of cancer-associated arterial disease, including cerebrovascular, coronary, and peripheral arterial events, requires that cardiovascular structures receive systematic attention on routine oncologic imaging. Interventional radiology contributes actively to CAT management through inferior vena cava filtration, catheter-directed thrombolysis, and thrombolytic-sparing mechanical thrombectomy, the latter being particularly relevant in oncology patients with elevated bleeding risk. Conclusions: Realizing the full potential of imaging in CAT requires not only technical proficiency with individual modalities but a synthesized, oncology-informed interpretive approach that incorporates the patient’s treatment history, biomarker status, and thrombotic risk profile at the time of image interpretation, positioning the radiologist as a central rather than peripheral figure in oncologic care. Full article

Background/Objectives: Pulmonary embolism (PE) is a major cause of cardiovascular mortality, particularly in high-risk cases complicated by hemodynamic instability. Systemic thrombolysis is the recommended treatment in such settings; however, the coexistence of thrombocytopenia represents a major therapeutic challenge due to concerns regarding bleeding risk. Evidence guiding thrombolytic therapy in thrombocytopenic patients with PE is limited. This study aimed to present a representative case and review the available literature addressing thrombolysis in PE complicated by thrombocytopenia. Methods: A qualitative review of published case reports was conducted using the PubMed and Scopus databases, and articles describing adult patients with objectively confirmed PE, documented thrombocytopenia, and treatment with thrombolytic therapy were included. Eight case reports met the inclusion criteria, and the clinical characteristics, severity markers, platelet dynamics, treatment strategies and outcomes were analyzed and compared with the reported case. Results: Most of the reported patients presented with high-risk pulmonary embolism, defined by hemodynamic instability, including shock or cardiac arrest. Thrombolysis was frequently administered despite platelet counts below conventional thresholds. Platelet levels at the time of thrombolysis varied widely, including cases of severe thrombocytopenia. Clinical and hemodynamic improvement was observed in most of the cases, while major bleeding complications were infrequent. The reported case demonstrated successful systemic thrombolysis with rt-PA in a postpartum patient with suspected heparin-induced thrombocytopenia and high-risk PE, without hemorrhagic events. Conclusions: Available evidence suggests that thrombolytic therapy may be a viable life-saving option in carefully selected thrombocytopenic patients with high-risk pulmonary embolism. Therapeutic decisions should prioritize clinical severity and hemodynamic status over platelet count alone, emphasizing individualized, multidisciplinary risk–benefit assessment. Full article

Background: In the treatment of ischemic stroke, both tissue-type plasminogen activator (t-PA) thrombolytic and endovascular therapy are employed; however, delayed intervention with these therapies increases the risk of hemorrhage. Hemorrhage associated with delayed t-PA treatment involves the activation of plasmin and matrix metalloproteinases (MMPs); however, the detailed mechanisms underlying I/R activation remain unclear. Objectives: This study examined the effects of delayed recanalization on ischemic stroke in a permanent middle cerebral artery (MCA) occlusion (MCA-O) model, and a novel MCA ischemia/reperfusion (I/R) model: 2-h ischemia followed by reperfusion (I/R 2 h), and 4.5-h ischemia followed by reperfusion (I/R 4.5 h). Secondary induced thrombus (SIT) formation, hemorrhage, MMP activity, MMP-9 immunoreactivity, and tomato lectin (TL) staining, as well as the effects of t-PA and heparin treatment were evaluated. Results: SIT formed within 1 h after reperfusion in the I/R 4.5 h model only, while t-PA or heparin treatment reduced SIT formation. Hemorrhage increased with or without t-PA administration in the I/R 4.5 h model, but it was suppressed by heparin pretreatment. MMP activity and MMP-9 immunoreactivity were localized to the SIT. Additionally, a negative staining area for TL was observed in the damaged area, where SIT formed in the I/R 4.5 h model. Conclusions: These results suggest that delayed recanalization induces SIT via glycocalyx degradation, leading to hemorrhage via plasmin/MMP-9 activation by endogenous and exogenous t-PA-mediated fibrinolysis in novel murine models of ischemic stroke. Furthermore, inhibition of SIT formation is beneficial for suppressing hemorrhages associated with delayed recanalization after endovascular or t-PA therapy. Full article

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (tPA) remains a keystone of acute ischemic stroke treatment but in a subset of patients is complicated by angioedema, a potentially life-threatening adverse event largely mediated by bradykinin signaling. The unpredictable and idiosyncratic nature of this reaction has long suggested an underlying genetic contribution, yet its molecular architecture has remained poorly characterized. We hypothesized that alteplase-associated angioedema represents a multigenic susceptibility phenotype, arising from the convergence of rare genetic variants across multiple interacting physiological systems rather than from a single causal variant. To explore this hypothesis, we performed clinical exome sequencing in a cohort of 11 patients who developed angioedema following alteplase administration. Rather than identifying a shared pathogenic variant, we observed distinct yet convergent patterns of genetic vulnerability, allowing patients to be grouped according to dominant, but overlapping, biological axes. These included alterations affecting bradykinin regulation (e.g., ACE, SERPING1, XPNPEP2), endothelial structure and hemostasis (e.g., VWF, COL4A1), neurovascular and calcium signaling (e.g., SCN10A, RYR1), and vascular repair or remodeling pathways (e.g., PSEN2, BRCA2). Notably, many of the identified variants were classified as Variant of Uncertain Significance (VUS) or likely benign significance in isolation. However, when considered within an integrated, pathway-based framework, these variants can be interpreted as capable of contributing cumulatively to system level fragility, a phenomenon best described as “contextual pathogenicity”. Under the acute biochemical and proteolytic stress imposed by thrombolysis, this reduced physiological reserve may allow otherwise compensated vulnerabilities to become clinically manifest. Together, these findings support a model in which severe alteplase-associated angioedema appears as an emergent property of interacting genetic networks, rather than a monogenic disorder. This systems level perspective underscores the limitations of gene centric interpretation for adverse drug reactions and highlights the potential value of pathway informed, multi-genic approaches to risk stratification. Such frameworks may ultimately contribute to safer, more personalized thrombolytic decision, while providing a conceptual foundation for future functional and translational studies. Full article

Feline cardiogenic arterial thromboembolism (ATE) is a severe complication of cardiac disease in cats, often causing severe clinical signs and poor prognosis. Despite its importance, standardized guidelines for prevention and treatment are lacking. This systematic review evaluated available evidence on preventive, acute, and chronic management strategies for feline cardiogenic ATE. A comprehensive search using PubMed, Scopus and Web of Science was performed, following PRISMA 2020 guidelines. Peer-reviewed studies investigating therapeutic interventions for ATE were included. Risk of bias was assessed using the SYRCLE tool. Nineteen studies involving 909 cats were included. Preventive therapy with clopidogrel and rivaroxaban improved survival. Acute multimodal treatment combining anticoagulant and antiplatelet drugs improved survival compared to monotherapy. Thrombolytic therapy showed some efficacy but had frequent severe complications. Long-term management with clopidogrel and rivaroxaban achieved the longest survival and lowest recurrence, while acetylsalicylic acid provided inconsistent benefits and more adverse effects. Eleven of the nineteen (58%) studies had high risk of bias due to small sample size and heterogeneous protocols. Current evidence supports dual therapy, particularly clopidogrel with rivaroxaban or enoxaparin, as the most effective and well-tolerated approach for prevention and treatment. Larger, standardized prospective trials are urgently needed to strengthen the evidence. Full article

Background: Central retinal artery occlusion (CRAO) is an ophthalmic emergency attributed to a vessel occlusion with an embolus or a thrombus and may occur during the hypercoagulable state, inflammation, or vasculitis. CRAO may occur in children; however its incidence is very rare. Most pediatric cases have detectable etiologies. Case Presentation: We describe the case of an otherwise-healthy six-year-old female, who presented with the sudden and complete vision loss of the left eye lasting over twelve hours after a six-day chickenpox exanthema, followed by a high fever. All the ophthalmological, laboratory, and instrumental investigations led to the diagnosis of a left CRAO. Laboratory testing was unremarkable except for the transient elevation of D dimers (1363 µg/L), IgM anticardiolipin antibodies (238.5 CU), and IgG anti-beta-2 glycoprotein-1 antibodies (76.1 CU) on admission. Thrombolytic treatment was not exerted because of late presentation to the hospital. Treatment with steroids, antiviral medications, antibiotics, and anticoagulants was obtained, but the visual outcome was poor during the hospitalization and at the last follow-up. We could not ascribe features of this case to any etiological condition apart from the documented ongoing chickenpox infection. Conclusions: This is the first case report of CRAO in a child with transient aPL elevation and acute chickenpox infection. Full article

Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide, requiring rapid reperfusion to minimize damage. Current treatments, including intravenous thrombolysis (IVT) with alteplase (rt-PA) and mechanical thrombectomy (MT), face limitations such as thrombolysis resistance, dosing complexity, and reduced efficacy in large vessel occlusions (LVOs) or fibrin-rich clots. Tenecteplase (TNK), a bioengineered thrombolytic agent with superior pharmacokinetics, simplified administration, and higher fibrin specificity, offers promising advantages over rt-PA, including potential synergy with MT and efficacy against resistant thrombi. Direct oral anticoagulants (DOACs) further complicate AIS management, but evidence suggests that DOAC-treated patients may experience better thrombolysis outcomes due to distinct thrombus characteristics. Advances in imaging now enable precise visualization of vessel occlusion and treatment effects, opening opportunities to refine therapies. Combination approaches targeting fibrin thrombus components may enhance thrombolysis and improve outcomes in resistant cases. Future research should explore TNK’s role in intra-arterial (IA) applications, combination therapies, and its interaction with MT to optimize reperfusion strategies. TNK’s simplified use and promising efficacy position it as a potential breakthrough in AIS management, with the potential to improve functional recovery and reduce treatment complexity. Full article

Background/Objectives: Thrombotic diseases, such as ischemic stroke, acute myocardial infarction, and venous thromboembolism, are leading causes of global morbidity and mortality. Traditional thrombolytic therapies like systemic tissue plasminogen activator (tPA) are limited by bleeding risks, poor targeting, and inconsistent efficacy. This review explores emerging non-pharmacological technologies aimed at overcoming these challenges through targeted, minimally invasive thrombolysis. Methods: A narrative synthesis of recent advancements was conducted, focusing on six innovative approaches: ultrasound-mediated thrombolysis (UMT), microrobots, electrothrombectomy, photothrombectomy, magnetic targeted thrombolysis, and nanotechnology. Preclinical and clinical studies were reviewed to assess mechanisms, efficacy, safety, and translational potential, prioritizing technologies with demonstrated success in animal or early human trials. Results: Technologies like microbubble-enhanced UMT, magnetically actuated microrobots, and fibrin-targeted nanoparticles showed promising results. UMT improved recanalization in ischemic stroke and pulmonary embolism, while electrothrombectomy demonstrated safe, effective clot extraction in human trials. However, challenges remain in scalability, biocompatibility, and clinical integration, with microrobots and photothrombectomy still in preclinical stages. Conclusions: Emerging thrombolysis technologies offer safer, more targeted alternatives to conventional treatments. Clinical adoption will depend on overcoming translational hurdles, including large-scale trials, miniaturization, and interdisciplinary collaboration, with a focus on hybrid approaches and real-time imaging integration. Full article

Ischemic stroke (IS) is a leading cause of mortality worldwide, responsible for approximately 55% of all neurological disabilities. Proper brain function requires continuous energy supply, primarily generated by mitochondria. Cerebral ischemia impairs the functioning of mitochondrial electron transport chain, reducing adenosine triphosphate production and increasing reactive oxygen species. Inflammation also plays a critical role throughout all stroke phases. YKL-40, a pro-inflammatory glycoprotein, serves as a biomarker of macrophage and microglial activation, while YKL-39 regulates autoimmunity, tissue remodeling, and exhibits monocyte chemotactic and pro-angiogenic activity. This study aims to investigate mitochondrial bioenergetics, oxidative stress, and inflammation in IS patients before and after thrombolysis. Bioenergetic parameters were assessed using Mito Stress Test on an Agilent Seahorse analyzer, and YKL-39, YKL-40 and 4-HNE plasma levels via ELISA. Pre-thrombolytic IS patients demonstrated significantly reduced basal respiration and spare respiratory capacity, along with lower plasma YKL-40 levels. In contrast, they exhibited higher plasma YKL-39 concentrations and increased oxidative stress marker 4-hydroxy-2-nonenal compared to post-thrombolytic patients. These findings highlight novel associations between mitochondrial dysfunction, oxidative stress, and inflammation in IS, and suggest that parameters reflecting these processes may serve as potential biomarkers for evaluating disease severity and predicting outcomes. Full article

In line with AHA/ASA guidance, intravenous alteplase has served as the standard first-line reperfusion treatment in acute ischemic stroke (AIS). Hemorrhagic transformation (HT) is a common spontaneous complication after thrombolytic therapy for AIS with increased mortality. Restoration of flow in an occluded artery can precipitate blood–brain barrier breakdown and heighten the risk of HT. However, the pathogenesis of HT is multifactorial, and identifying patients at high risk after recanalization therapy (RT) has a defining role in ensuring optimal treatment. At the same time, it is still under debate how these patients can best be identified based on clinical and biological characteristics. Preventing HT will become increasingly essential. In this review, our primary objective was to identify research focused on the cardiovascular risk factors predicting HT after AIS treated with thrombolytics, as this may help develop targeted treatment strategies and diminish the risk of HT. Full article

Background/Objectives: Acute ischemic stroke (AIS) remains a major cause of morbidity and mortality worldwide. Although advanced imaging modalities, such as CT perfusion (CTP), are increasingly being used in clinical decision-making, the necessity and added value of perfusion imaging prior to intravenous thrombolysis (IVT) within early time windows remains uncertain. We aim to evaluate the safety and functional outcomes of IVT in AIS patients without perfusion deficits on CTP. We question the requirement of perfusion mismatch for IVT eligibility and hypothesize that IVT is safe and beneficial even in the absence of a perfusion deficit. Methods: A retrospective analysis was conducted using data from the Giessen Stroke Registry, focusing on AIS patients who underwent CTP imaging and received IVT between 01/2018 and 12/2020. Patients who underwent endovascular therapy were excluded. Clinical data, including demographics, National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Scale (mRS) scores, and complications, were collected. Patients were dichotomized based on the presence of perfusion lesions and compared in terms of efficacy outcomes (i.e., NIHSS or mRS improvement during the hospital stay) and safety outcomes (i.e., post-thrombolytic hemorrhagic complications). Results: Of the 89 AIS patients with available CTP data who received IVT, 34 (38%) had a perfusion deficit and 55 (62%) did not. There were no significant differences between the groups in terms of hemorrhagic complications or functional outcomes at discharge (NIHSS and mRS). Clinical improvement from admission to discharge was similar in both groups. Conclusions: Our findings suggest that IVT is safe and clinically effective even in AIS patients without detectable perfusion deficits on CTP within the standard therapeutic window. These results support current guideline recommendations that do not mandate perfusion imaging for early presenters. Routine use of CTP in this context may be of limited clinical utility and could unnecessarily delay treatment or introduce additional risks in the first 4.5 h. Full article

Background/Objectives: While intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke (AIS) within 4.5 h of symptom onset, many patients present beyond this time window. Recent trials suggest that IVT may be both effective and safe in selected patients treated after the standard time window. Methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov for randomized-controlled clinical trials (RCTs) and individual patient-data meta-analyses (IPDMs) of RCTs comparing IVT plus best medical treatment (BMT) to BMT alone in AIS patients who were last-known-well more than 4.5 h earlier. The primary efficacy outcome was a 90-day excellent functional outcome [modified Rankin Scale (mRS)-scores of 0–1]. Secondary efficacy outcomes included good functional outcome (mRS-scores 0–2) and reduced disability (≥1-point reduction across all mRS-strata). The primary safety outcome was symptomatic intracranial hemorrhage (sICH); secondary safety outcomes were any ICH and 3-month all-cause mortality. Subgroup analyses were performed stratified by different thrombolytics, time-windows, imaging modalities, and affected circulation. Results: Nine studies were included, comprising 1660 patients in the IVT-group and 1626 patients in the control-group. IVT significantly improved excellent functional outcome (RR = 1.24; 95%CI:1.14–1.34; I² = 0%) and good functional outcome (RR = 1.18; 95%CI:1.05–1.33; I² = 70%). IVT was associated with increased odds of reduced disability (common OR = 1.3; 95%CI:1.15–1.46; I² = 0%) and increased risk of sICH (RR = 2.75; 95%CI:1.49–5.05; I² = 0%). The rates of any ICH and all-cause mortality were similar between the two groups. No significant subgroup differences were documented. Conclusions: IVT in the extended time window improved functional outcomes without increasing mortality, despite a higher rate of sICH. Full article

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

This study aimed to characterize and evaluate the fibrinolytic, thrombolytic, hematological, and toxicological aspects of a serine protease (AsKSP) from Aspergillus tamarii Kita UCP 1279. The enzyme was purified using a two-phase aqueous system and assessed for optimal pH (7.0) and temperature (50 °C), stability, and effects of metal ions, inhibitors, and surfactants. AsKSP exhibited stability for up to 120 min at 50 °C and 36 h at pH 7.0. Enzymatic activity was enhanced by Na⁺ and Zn²⁺ and non-ionic surfactants (Tween-80) but inhibited by Cu²⁺, Fe³⁺, Triton X-100, and SDS, reducing activity by up to 62.35%. The highest amidolytic activity was observed for the substrate N-succinyl-Gly–Gly–Phe-p-nitroanilide. SDS-PAGE analysis indicated an approximate molecular mass of 90 kDa. The enzyme showed fibrinolytic activity, degrading 38.81% of fibrin clots in vitro after 90 min, without affecting fibrinogen. Cytotoxicity assays indicated no toxicity (cell viability > 80%). Coagulation assays showed slight prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT), with no effect on thrombin time. No red blood cell lysis was observed, and albumin increased enzymatic activity by 31.70%. These findings demonstrate that Aspergillus tamarii Kita UCP 1279 produces a fibrinolytic protease with potential for thrombus treatment, providing a promising foundation for drug development. Full article