RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Thrombosis is a common cause of morbidity and mortality worldwide. Lagopsis supina (Stephan ex Willd.) Ikonn.-Gal. ex Knorring is an ancient Chinese herbal medicine used for treating thrombotic diseases. Nevertheless, the antithrombotic mechanisms and effective constituents of this plant have not been clarified. AIM OF THE STUDY: This work aimed to elucidate the pharmacodynamics and mechanism of L. supina against thrombosis. MATERIALS AND METHODS: Systematic network pharmacology was used to explore candidate effective constituents and hub targets of L. supina against thrombosis. Subsequently, the binding affinities of major constituents with core targets were verified by molecular docking analysis. Afterward, the therapeutic effect and mechanism were evaluated in an arteriovenous bypass thrombosis rat model. In addition, the serum metabolomics analysis was conducted using ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrometry. RESULTS: A total of 124 intersected targets of L. supina against thrombosis were predicted. Among them, 24 hub targets were obtained and their mainly associated with inflammation, angiogenesis, and thrombosis approaches. Furthermore, 9 candidate effective constituents, including (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol, aurantiamide, (22E,24R)-5α,8α-epidioxyergosta-6,9 (11),22-trien-3ß-ol, lagopsinA, lagopsin C, 15-epi-lagopsin C, lagopsin D, 15-epi-lagopsin D, and lagopsin G in L. supina and 6 potential core targets (TLR-4, TNF-α, HIF-1α, VEGF-A, VEGFR-2, and CLEC1B) were acquired. Then, these 9 constituents demonstrated strong binding affinities with the 6 targets, with their lowest binding energies were all less than -5.0 kcal/mol. The antithrombotic effect and potential mechanisms of L. supina were verified, showing a positively associated with the inhibition of inflammation (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) and coagulation cascade (TT, APTT, PT, FIB, AT-III), promotion of angiogenesis (VEGF), suppression of platelet activation (TXB2, 6-keto-PGF1α, and TXB2/6-keto-PGF1α), and prevention of fibrinolysis (t-PA, u-PA, PAI-1, PAI-1/t-PA, PAI-1/u-PA, and PLG). Finally, 14 endogenous differential metabolites from serum samples of rats were intervened by L. supina based on untargeted metabolomics analysis, which were closely related to amino acid metabolism, inflammatory and angiogenic pathways. CONCLUSION: Our integrated strategy based on network pharmacology, molecular docking, metabolomics, and in vivo experiments revealed for the first time that L. supina exerts a significant antithrombotic effect through the inhibition of inflammation and coagulation cascade, promotion of angiogenesis, and suppression of platelet activation. This paper provides novel insight into the potential of L. supina as a candidate agent to treat thrombosis.
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Fibrinolíticos , Metabolómica , Simulación del Acoplamiento Molecular , Farmacología en Red , Ratas Sprague-Dawley , Trombosis , Animales , Fibrinolíticos/farmacología , Fibrinolíticos/química , Fibrinolíticos/aislamiento & purificación , Ratas , Masculino , Trombosis/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/químicaRESUMEN
AIM: To identify the factors associated with thrombosis in dialysis patients. BACKGROUND: Thrombosis is a leading cause of vascular access failure in dialysis patients. Numerous risk factors contribute to thrombosis in this population. METHODS: A systematic search was conducted across international databases using standardized keywords. The quality of the selected studies was assessed using the STROBE and CONSORT checklists. The findings were summarized in a Garrard table. Meta-analysis was performed using CMA software. The study adhered to the guidelines outlined in the PRISMA statement. RESULTS: A total of 180 articles were reviewed. The odds ratio for thrombosis in patients with arteriovenous grafts compared to arteriovenous fistulas was 10.93 (95 % CI: 9.35-12.78), demonstrating statistical significance (P = 0.001). Similarly, hemodialysis patients had an odds ratio of thrombosis 3.60 times higher than non-hemodialysis patients (95 % CI: 3.54-4.19), with statistical significance (P = 0.001). Patients undergoing single-stage basilic vein transposition had a 1.89 times higher risk of thrombosis compared to those undergoing two-stage transposition (95 % CI: 1.04-3.46), also demonstrating statistical significance (P = 0.038). CONCLUSIONS: Thrombosis in patients with end-stage renal disease undergoing dialysis was significantly associated with various factors, including graft access, single-stage basilic vein transposition, and hemodialysis. Additional contributing factors to thrombosis included diabetes, elevated homocysteine levels, female gender, age over 50, access location, and low access blood flow velocity. The analysis revealed a higher incidence of thrombosis in end-stage renal disease patients undergoing hemodialysis compared to those not undergoing dialysis, as well as in patients with arteriovenous grafts compared to those with arteriovenous fistulas. These findings underscore the importance of recognizing and managing these risk factors to prevent thrombotic events and enhance patient care within the dialysis setting.
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Diálisis Renal , Trombosis , Humanos , Diálisis Renal/efectos adversos , Factores de Riesgo , Trombosis/etiología , Derivación Arteriovenosa Quirúrgica/efectos adversos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicacionesRESUMEN
Concomitant direct oral anticoagulants (DOACs) and tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (anti-VEGF TKI) have been associated with a higher risk of bleeding. Nevertheless, concomitant administration seems frequent in clinical practice in patients with cancer-associated thrombosis and appears to be safe according to the retrospective study by Boileve A. et al. But the risk of an additional pharmacokinetic interaction between anti-VEGF TKI and DOACs must be considered, in case of P-glycoprotein (P-gp) inhibition by the TKI. We describe a case report with a major bleeding event in a renal metastatic cancer patient treated with cabozantinib and rivaroxaban. This case highlights the difficult therapeutic decision in a complex patient with cancer-associated thrombosis, who refused the anticoagulant subcutaneous route. Accumulation of bleeding risk factors (genito-urinary tumor localization) was additive to several pharmacodynamic interactions (acetylsalicylic acid, venlafaxine) and a potential pharmacokinetic interaction between cabozantinib and rivaroxaban. Indeed, cabozantinib-related P-glycoprotein inhibition could have led to a supratherapeutic level of rivaroxaban, contributing partly to the bleeding event. Before combining an anti-VEGF TKI and DOACs, a multidisciplinary pretherapeutic assessment seems crucial to evaluate the patient's bleeding risk factors, pharmacodynamic interactions, and the risk of pharmacokinetic interactions mediated by P-gp.
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Anticoagulantes , Interacciones Farmacológicas , Piridinas , Rivaroxabán , Humanos , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Estudios Retrospectivos , Piridinas/efectos adversos , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Piridinas/farmacocinética , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/farmacocinética , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anilidas/administración & dosificación , Anilidas/efectos adversos , Anilidas/farmacocinética , Hemorragia/inducido químicamente , Neoplasias Renales/tratamiento farmacológico , Masculino , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacocinética , Trombosis/inducido químicamente , Trombosis/etiología , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Administración Oral , AncianoRESUMEN
Percutaneous coronary and structural heart interventions are increasingly preferred over cardiac surgery due to reduced rates of periprocedural complications and faster recovery but often require postprocedural antithrombotic therapy for the prevention of local thrombotic events. Antithrombotic therapy is inevitably associated with increased bleeding, the extent of which is proportional to the number, duration, and potency of the antithrombotic agents used. Bleeding complications have important clinical implications, which may outweigh the expected benefit of reducing thrombotic events. Herein, we provide a comprehensive description of the classification and clinical relevance of high bleeding risk in patients undergoing coronary and structural heart interventions.
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Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Hemorragia/epidemiología , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Medición de Riesgo/métodos , Trombosis/prevención & control , Trombosis/etiología , Trombosis/epidemiología , Procedimientos Quirúrgicos Cardíacos/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversosRESUMEN
Percutaneous left atrial appendage closure (LAAC) is a valid alternative to oral anticoagulation to prevent ischemic stroke in patients with atrial fibrillation.The devices approved in Europe and United States for percutaneous LAAC contain metal and temporary antithrombotic therapy is strongly recommended following implantation to prevent thrombus formation on the atrial device surface. There is still uncertainty regarding to the optimal antithrombotic drug regimen after device implantation for several reasons. Thus, this review aims at summarizing the available evidence and the remaining challenges related to the management of antithrombotic therapy in the context of LAAC procedure.
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Apéndice Atrial , Fibrilación Atrial , Fibrinolíticos , Humanos , Apéndice Atrial/cirugía , Fibrilación Atrial/complicaciones , Fibrilación Atrial/cirugía , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Cateterismo Cardíaco/métodos , Dispositivo Oclusor Septal , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Accidente Cerebrovascular Isquémico/prevención & control , Trombosis/prevención & control , Trombosis/etiologíaRESUMEN
Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice.
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Fibrinolíticos , Enfermedad Arterial Periférica , Humanos , Enfermedad Arterial Periférica/cirugía , Fibrinolíticos/uso terapéutico , Trombosis/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/cirugía , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Rivaroxabán/uso terapéutico , Rivaroxabán/administración & dosificaciónRESUMEN
PURPOSE: To explore the behavioral intention of breast cancer patients undergoing chemotherapy to prevent PICC-related thrombosis based on the theory of planned behavior (TPB). METHODS: This qualitative study employed purposive sampling and conducted semi-structured interviews with 14 breast cancer patients undergoing chemotherapy in the outpatient chemotherapy ward of a tertiary A-level comprehensive hospital in Beijing from July to August 2023. Data were analyzed using Colaizzi's descriptive analysis framework. RESULTS: Data analysis identified 10 themes that were derived from 4 aspects. Regarding behavioral attitude, three themes were condensed: (1) Considering the benefits of preventive measures, (2) Simple and easy preventive measures, and (3) Underestimating the importance of PICC-related thrombosis prophylaxis. Subjective norms yielded two main themes and five sub-themes: (1) Support from those close to the patient motivates adherence to prophylaxis (support from the patient's family, healthcare professionals, and other patients) and (2) Patients are influenced by personal factors to form an internal driving force (physical symptoms, fear of PICC-related thrombosis). Regarding perceived behavioral control, three main themes and four sub-themes were extracted: (1) Obstacles before actual prevention exercise (prevention information, hard-to-remember information), (2) Forgetfulness is the main obstacle factor, and (3) Wanting to overcome barriers to adhere to regular prevention (confidence to overcome obstacles, hope to get support). CONCLUSIONS: The impediments and facilitators identified in this study may provide a scientific foundation for subsequent targeted non-pharmacological preventive interventions for PICC-related thrombosis based on TPB in breast cancer patients undergoing chemotherapy. Special interventions should be designed for the patients in three areas: the patients themselves, the supporters around the patient, and the healthcare professionals.
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Neoplasias de la Mama , Intención , Investigación Cualitativa , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Trombosis/prevención & control , Trombosis/etiología , Anciano , Entrevistas como Asunto , Teoría del Comportamiento PlanificadoRESUMEN
BACKGROUND: Ball thrombus is rare and life-threatening. The correct diagnosis and timely management are key to improving patient prognosis. Here, we present a case report and literature review of ball thrombus. CASE PRESENTATION: A 75-year-old woman presented to our outpatient clinic because of palpitations and chest distress for 8 months. She was diagnosed mitral stenosis, and transthoracic echocardiography (TTE) showed a round mass attached to the left atrial (LA) wall. Before anesthesia induction, TTE found that the mass has dropped from the LA wall, and was spinning in the LA causing intermittent obstruction of the valve. Anesthesia induction was then carried out under TTE monitoring, and transesophageal echocardiograph found another mass in the LA appendage after intubation. She underwent LA mass removal and mitral valve replacement, and was discharged uneventfully. Histopathology confirmed the diagnosis of thrombus. Our literature review identified 19 cases of ball thrombus between 2015 and 2024. The average age was 54.8 (range 3-88) years. Heart failure was present as the initial symptom in 11 cases, and most patients had mitral valve disease or concomitant with atrial fibrillation. 12 cases received surgery, and 7 received medical treatment only. 2 deaths occurred, one due to the obstruction of left ventricular inflow tract and the other due to the worsening of heart failure. CONCLUSION: Ball thrombus is rare in clinical settings. Urgent thrombectomy should be performed as soon as possible, and echocardiography can be used for real-time monitoring during surgery.
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Trombosis , Humanos , Femenino , Anciano , Trombosis/diagnóstico por imagen , Trombosis/cirugía , Estenosis de la Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/diagnóstico por imagen , Ecocardiografía Transesofágica/métodos , Ecocardiografía , Implantación de Prótesis de Válvulas Cardíacas , Cardiopatías/diagnósticoRESUMEN
Heart failure, broadly characterized by the gradual decline of the ability of the heart to maintain adequate blood flow throughout the body's vascular network of veins and arteries, is one of the leading causes of death worldwide. Mechanical Circulatory Support is one of the few available alternative interventions for late-stage heart failure with reduced ejection fraction. A ventricular assist device is surgically implanted and connected to the left and or right heart ventricles to provide additional bloodflow, off-loading the work required by the heart to maintain circulation. Modern mechanical circulatory support devices generate non-physiological flow conditions that can lead to the damage and rupture of blood cells (hemolysis), and the formation of blood clots (thrombosis), which pose severe health risks to the patient. It is essential to improve prediction tools for blood damage to reduce the risk of hemolysis and thrombosis. A simulation-based approach examines the interaction between hemolysis and thrombosis. Incompressible finite-volume computational fluid dynamics simulations are executed on an open-hub axial flow ventricular assist device. A continuum model of thrombosis and the intrinsic coagulation process is extended to include the effect of hemolysis. The model accounts for the effect of activation of platelets by shear stress, paracrine signaling, adhesion, and hemoglobin and ADP released during hemolysis. The effect of hemolysis with thrombosis is modelled by accounting for the hyper-adhesivity of von-Willebrand Factor on extracellular hemoglobin, and the increased rate of platelet activation induced by ADP release. Thrombosis is assessed at varying inflow rates and rotor speeds, and cases are executed where thrombosis is affected by ADP release and Hb-induced hyper-adhesivity. It is found that there is a non-negligible effect from hemolysis on thrombosis across a range of rotor speeds, and that hyperadhesivity plays a dominant role in thrombus formation in the presence of hemolysis.
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Corazón Auxiliar , Hemólisis , Trombosis , Trombosis/fisiopatología , Corazón Auxiliar/efectos adversos , Humanos , Hidrodinámica , Modelos Biológicos , Simulación por ComputadorRESUMEN
BACKGROUND AND OBJECTIVES: Ischemic stroke, a leading cause of mortality, necessitates understanding its mechanism for effective prevention. Echocardiography, especially transesophageal echocardiography (TEE), is the gold standard for detection of cardiac sources of stroke including left atrial thrombus, although its invasiveness, operator skill dependence, and limited availability in some centers prompt exploration of alternatives, such as cardiac CT (CCT). We conducted a systematic review and meta-analysis assessing the ability of CCT in the detection of intracardiac thrombus compared with echocardiography. METHODS: We searched 4 databases up through September 8, 2023. Major search terms included a combination of the terms "echocardiograph," "CT," "TEE," "imaging," "stroke," "undetermined," and "cryptogenic." The current systematic literature review of the English language literature was reported in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. We assessed risk of bias using the QUADAS-2 tool and used random-effects meta-analysis to calculate different diagnostic metrics. RESULTS: The meta-analysis investigating CCT vs echocardiography for intracardiac thrombus detection yielded a total of 43 studies of 9,552 patients. Risk-of-bias assessment revealed a predominantly low risk of bias in the flow and timing, index test, and patient selection domains and a predominantly unclear risk of bias in the reference standard domain. The analysis revealed an overall sensitivity of 98.38% (95% CI 89.2-99.78) and specificity of 96.0% (95% CI 92.55-97.88). Subgroup analyses demonstrated that delayed-phase, electrocardiogram-gated CCT had the highest sensitivity (100%; 95% CI 0-100) while early-phase, nongated CCT exhibited a sensitivity of 94.31% (95% CI 28.58-99.85). The diagnostic odds ratio was 98.59 (95% CI 44.05-220.69). Heterogeneity was observed, particularly in specificity and diagnostic odds ratio estimates. DISCUSSION: CCT demonstrates high sensitivity, specificity, and diagnostic odds ratios in detecting intracardiac thrombus compared with traditional echocardiography. Limitations include the lack of randomized controlled studies, and other cardioembolic sources of stroke such as valvular disease, cardiac function, and aortic arch disease were not examined in our analysis. Large-scale studies are warranted to further evaluate CCT as a promising alternative for identifying intracardiac thrombus and other sources of cardioembolic stroke.
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Ecocardiografía , Cardiopatías , Accidente Cerebrovascular Isquémico , Trombosis , Humanos , Trombosis/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Ecocardiografía/métodos , Cardiopatías/diagnóstico por imagen , Cardiopatías/complicaciones , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. METHODS: This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. RESULTS: The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). CONCLUSION: Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.
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Plaquetas , Linfocitos , Neutrófilos , Embolia Pulmonar , Humanos , Embolia Pulmonar/sangre , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedad Aguda , Anciano , Trombosis/sangre , Trombosis/etiología , Medición de Riesgo/métodos , AdultoRESUMEN
BACKGROUND: Although femoropopliteal-specific stents have durable patency, stent thrombosis (ST) may occur, which can lead to acute limb ischaemia (ALI). AIMS: We aimed to investigate the clinical features and outcomes of ALI caused by femoropopliteal ST in patients with lower extremity artery disease. METHODS: This multicentre retrospective study included 499 patients with ALI - of whom 108 patients had ALI caused by femoropopliteal ST (ST-ALI) and 391 patients had ALI caused by other aetiologies (de novo ALI) - who underwent treatment between September 2011 and March 2023. Clinical features and outcomes were compared between the two groups. The primary outcome measure was 12-month amputation-free survival; factors associated with amputation or death were investigated using multivariate Cox proportional hazards regression analysis. RESULTS: Patients with ST-ALI were significantly more likely to exhibit conventional atherosclerotic risk factors, including diabetes mellitus (63% vs 26%) and haemodialysis (51% vs 10%) compared to patients with de novo ALI, whereas patients with de novo ALI were older (80 years vs 74 years) and more likely to have atrial fibrillation (49% vs 18%) than patients with ST-ALI. The 12-month amputation-free survival rate was significantly lower in the ST-ALI group than that in the de novo ALI group (51% vs 76%; p<0.001). Multivariate analysis revealed that ST-ALI, older age, haemodialysis, atrial fibrillation, the presence of a wound, peak C-reactive protein level, and non-ambulatory status all have an independent, positive association with death or major amputation. CONCLUSIONS: The current study revealed that patients with ST-ALI had worse clinical outcomes than those with de novo ALI, highlighting the need to maximise ST prevention.
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Amputación Quirúrgica , Arteria Femoral , Isquemia , Enfermedad Arterial Periférica , Arteria Poplítea , Stents , Trombosis , Humanos , Masculino , Anciano , Femenino , Estudios Retrospectivos , Arteria Poplítea/cirugía , Isquemia/terapia , Isquemia/mortalidad , Isquemia/etiología , Isquemia/cirugía , Arteria Femoral/cirugía , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/cirugía , Enfermedad Arterial Periférica/mortalidad , Anciano de 80 o más Años , Persona de Mediana Edad , Trombosis/etiología , Trombosis/mortalidad , Resultado del Tratamiento , Factores de Riesgo , Recuperación del Miembro , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/efectos adversos , Extremidad Inferior/irrigación sanguínea , Enfermedad Aguda , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: While surgery still remains the gold standard treatment for mechanical prosthetic valve thrombosis (MPVT) by many guidelines, the ultraslow low-dose thrombolytic regimen has been reported as a promising alternative. METHODS: In this prospective single-center cohort, patients with acute MPVT were treated with an ultraslow low-dose thrombolytic regimen consisting of 25 mg infusion of recombinant tissue-type plasminogen activator (rtPA) over 25 h. The regimen could be repeated in case of failure until resolution/occurrence of adverse events or a maximum cumulative dose of 150 mg. The primary outcome was the complete MPVT resolution rate; other outcomes included first-dose success rate, major bleeding, thromboembolic events, mortality, and total thrombolytic dose/duration. RESULTS: Between April 2018 to January 2024, 135 episodes of acute MPVT were treated with an ultraslow low-dose thrombolytic regimen in 118 patients. In 118/135 (87.4 %) episodes, right-sided prosthetic valve was involved. Complete success was achieved in 88.1 % of cases, with 39.5 % responding after the first dose. The median total dose was 50 mg over a median of 30 h. Only one fatal intracranial hemorrhage occurred (0.7 %), with no other bleeding or thromboembolic complications. CONCLUSION: The ultraslow low-dose thrombolytic regimen appears to exhibit high efficacy and acceptable safety in treating acute MPVT. Further large clinical trials are essential for validating these preliminary findings.
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Fibrinolíticos , Prótesis Valvulares Cardíacas , Terapia Trombolítica , Trombosis , Humanos , Femenino , Masculino , Estudios Prospectivos , Terapia Trombolítica/métodos , Prótesis Valvulares Cardíacas/efectos adversos , Persona de Mediana Edad , Trombosis/tratamiento farmacológico , Trombosis/etiología , Fibrinolíticos/administración & dosificación , Fibrinolíticos/uso terapéutico , Anciano , Estudios de Cohortes , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Relación Dosis-Respuesta a Droga , Resultado del Tratamiento , Enfermedad AgudaRESUMEN
SOURCE CITATION: Connolly SJ, Sharma M, Cohen AT, et al; ANNEXA-I Investigators. Andexanet for factor Xa inhibitor-associated acute intracerebral hemorrhage. N Engl J Med. 2024;390:1745-1755. 38749032.
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Inhibidores del Factor Xa , Trombosis , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Humanos , Trombosis/inducido químicamente , Hemorragia Cerebral/inducido químicamente , Masculino , Proteínas Recombinantes , Factor XaRESUMEN
OBJECTIVE: To investigate the effects of platelet-specific Rictor knockout on platelet activation and thrombus formation in mice. METHODS: PF4-Cre and Rictorfl/fl transgenic mice were crossed to obtain platelet-specific Rictor knockout (Rictor-KO) mice and wild-type mice (n=65), whose expression levels of Rictor, protein kinase B (AKT) and p-AKT were detected using Western blotting. Platelet counts of the mice were determined using routine blood tests, and hemostatic function was assessed by tail vein hemorrhage test. Venous thrombosis models were established in the mice to evaluate the effect of Rictor knockout on thrombosis. Platelet aggregation induced by ADP and thrombin was observed in Rictor-KO and wild-type mice, and flow cytometry was used to analyze the expression levels of integrin αIIbß3 and CD62P in resting and activated platelets. Plasma PF4 levels were determined with ELISA. Megakaryocytes from Rictor-KO and wild-type mice were incubated by vWF immunohistochemical antibody and APC-CD41 antibody to detect the number and ploidy of megakaryocytes, respectively. Platelet elongation on collagen surface was observed with scanning electron microscopy. RESULTS: Compared with the wild-type mice, Rictor-KO mice showed significantly decreased AKT phosphorylation, decreased platelet production, reduced thrombosis, and decreased platelet activation in response to ADP and thrombin stimulation. The Rictor-KO mice also showed lowered expression level of P-selectin protein and activation of integrin αIIbß3 with suppression of platelet extension, reduced plasma PF4 level and decreased number of megakaryocytes in the bone marrow. The ploidy of megakaryocytes and the mean area of proplatelets were both significantly decreased in Rictor-KO mice. CONCLUSION: Platelet-specific Rictor knockout inhibits platelet generation and activation to result in decreased thrombus formation in mice, suggesting the potential of mTORC2 activity inhibition as an efficient antithrombotic strategy.
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Plaquetas , Megacariocitos , Ratones Noqueados , Activación Plaquetaria , Proteínas Proto-Oncogénicas c-akt , Proteína Asociada al mTOR Insensible a la Rapamicina , Trombosis , Animales , Ratones , Proteína Asociada al mTOR Insensible a la Rapamicina/metabolismo , Proteína Asociada al mTOR Insensible a la Rapamicina/genética , Plaquetas/metabolismo , Trombosis/metabolismo , Trombosis/prevención & control , Megacariocitos/metabolismo , Megacariocitos/citología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Agregación Plaquetaria , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/genética , Selectina-P/metabolismo , Recuento de PlaquetasRESUMEN
BACKGROUND: This review article discussed the use of bridging therapy with low-molecular-weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI). HYPOTHESES: Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy. RESULTS: This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population. CONCLUSION: The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision-making and improve patient outcomes.