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1.
Platelets ; 35(1): 2344512, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38722090

RESUMEN

The last decade has seen increasing use of advanced imaging techniques in platelet research. However, there has been a lag in the development of image analysis methods, leaving much of the information trapped in images. Herein, we present a robust analytical pipeline for finding and following individual platelets over time in growing thrombi. Our pipeline covers four steps: detection, tracking, estimation of tracking accuracy, and quantification of platelet metrics. We detect platelets using a deep learning network for image segmentation, which we validated with proofreading by multiple experts. We then track platelets using a standard particle tracking algorithm and validate the tracks with custom image sampling - essential when following platelets within a dense thrombus. We show that our pipeline is more accurate than previously described methods. To demonstrate the utility of our analytical platform, we use it to show that in vivo thrombus formation is much faster than that ex vivo. Furthermore, platelets in vivo exhibit less passive movement in the direction of blood flow. Our tools are free and open source and written in the popular and user-friendly Python programming language. They empower researchers to accurately find and follow platelets in fluorescence microscopy experiments.


In this paper we describe computational tools to find and follow individual platelets in blood clots recorded with fluorescence microscopy. Our tools work in a diverse range of conditions, both in living animals and in artificial flow chamber models of thrombosis. Our work uses deep learning methods to achieve excellent accuracy. We also provide tools for visualizing data and estimating error rates, so you don't have to just trust the output. Our workflow measures platelet density, shape, and speed, which we use to demonstrate differences in the kinetics of clotting in living vessels versus a synthetic environment. The tools we wrote are open source, written in the popular Python programming language, and freely available to all. We hope they will be of use to other platelet researchers.


Asunto(s)
Plaquetas , Aprendizaje Profundo , Trombosis , Plaquetas/metabolismo , Trombosis/sangre , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Animales , Ratones , Algoritmos
2.
Ann Card Anaesth ; 27(1): 68-69, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38722126

RESUMEN

ABSTRACT: The occurrence of pulmonary artery thrombus in association with rheumatic mitral stenosis is a rare complication. Pulmonary artery thrombus formation may worsen pulmonary artery pressures, and this may precipitate acute right heart failure. The possible mechanisms behind pulmonary artery thrombus formation during mitral valve replacement surgery could be acute coagulopathy following surgery, the presence of chronic pulmonary thromboembolism, or chronic atrial fibrillation. We report an unusual case of pulmonary artery thrombus in a patient with rheumatic MS which was diagnosed with transoesophageal echocardiography after MVR.


Asunto(s)
Diagnóstico Tardío , Ecocardiografía Transesofágica , Implantación de Prótesis de Válvulas Cardíacas , Válvula Mitral , Arteria Pulmonar , Trombosis , Humanos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Arteria Pulmonar/diagnóstico por imagen , Ecocardiografía Transesofágica/métodos , Trombosis/diagnóstico por imagen , Trombosis/etiología , Válvula Mitral/cirugía , Válvula Mitral/diagnóstico por imagen , Estenosis de la Válvula Mitral/cirugía , Femenino , Cardiopatía Reumática/complicaciones , Cardiopatía Reumática/cirugía , Embolia Pulmonar/etiología , Embolia Pulmonar/diagnóstico por imagen , Persona de Mediana Edad
3.
Comput Methods Programs Biomed ; 250: 108186, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692252

RESUMEN

BACKGROUND AND OBJECTIVES: Venovenous Extracorporeal Membrane Oxygenation (VV ECMO) provides respiratory support to patients with severe lung disease failing conventional medical therapy. An essential component of the ECMO circuit are the cannulas, which drain and return blood into the body. Despite being anchored to the patient to prevent accidental removal, minor cannula movements are common during ECMO. The clinical and haemodynamic consequences of these small movements are currently unclear. This study investigated the risk of thrombosis and recirculation caused by small movements of a dual lumen cannula (DLC) in an adult using computational fluid dynamics. METHODS: The 3D model of an AVALON Elite DLC (27 Fr) and a patient-specific vena cava and right atrium were generated for an adult patient on ECMO. The baseline cannula position was generated where the return jet enters the tricuspid valve. Alternative cannula positions were obtained by shifting the cannula 5 and 15 mm towards inferior (IVC) and superior (SVC) vena cava, respectively. ECMO settings of 4 L/min blood flow and pulsatile flow at SVC and IVC were applied. Recirculation was defined as a scalar value indicating the infused oxygenated blood inside the drainage lumen, while thrombosis risk was evaluated by shear stress, stagnation volume, washout, and turbulent kinetic energy. RESULTS: Recirculation for all models was less than 3.1 %. DLC movements between -5 to 15 mm increased shear stress and turbulence kinetic energy up to 24.7 % and 11.8 %, respectively, compared to the baseline cannula position leading to a higher predicted thrombosis risk. All models obtained a complete washout after nine seconds except for when the cannula migrated 15 mm into the SVC, indicating persisting stasis and circulating zones. CONCLUSION: In conclusion, small DLC movements were not associated with an increased risk of recirculation. However, they may increase the risk of thrombosis due to increased shear rate, turbulence, and slower washout of blood. Developing effective cannula securement devices may reduce this risk.


Asunto(s)
Cánula , Oxigenación por Membrana Extracorpórea , Hidrodinámica , Oxigenación por Membrana Extracorpórea/instrumentación , Humanos , Trombosis/etiología , Trombosis/prevención & control , Simulación por Computador , Adulto , Hemodinámica , Modelos Cardiovasculares
4.
J Cardiothorac Surg ; 19(1): 292, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760659

RESUMEN

BACKGROUND: Although well-known for their thromboresistance, bileaflet mechanical heart valves (BMHV) require lifelong anti-thrombotic therapy. This must be associated with a certain level of thrombogenicity. Since both thromboresistance and thrombogenicity are explained by the blood-artificial surface or liquid-solid interactions, the aim of the present study was to explore BMHV thromboresistance from new perspectives. The wettability of BMHV pyrolytic carbon (PyC) occluders was investigated in under-liquid conditions. The submerged BMHV wettability clarifies the mechanisms involved in the thromboresistance. METHODS: The PyC occluders of a SJM Regent™ BMHV were previously laser irradiated, to create a surface hierarchical nano-texture, featuring three nano-configurations. Additionally, four PyC occluders of standard BMHV (Carbomedics, SJM Regent™, Bicarbon™, On-X®), were investigated. All occluders were evaluated in under-liquid configuration, with silicon oil used as the working droplet, while water, simulating blood, was used as the surrounding liquid. The under-liquid droplet-substrate wetting interactions were analyzed using contact angle goniometry. RESULTS: All the standard occluders showed very low contact angle, reflecting a pronounced affinity for non-polar molecules. No receding of the contact line could be observed for the untreated occluders. The smallest static contact angle of around 61° could be observed for On-X® valve (the only valve made of full PyC). The laser-treated occluders strongly repelled oil in underwater conditions. A drastic change in their wetting behaviour was observed depending on the surrounding fluid, displaying a hydrophobic behaviour in the presence of air (as the surrounding medium), and showing instead a hydrophilic nature, when surrounded by water. CONCLUSIONS: BMHV "fear" water and blood. The intrinsic affinity of BMHV for nonpolar fluids can be translated into a tendency to repel polar fluids, such as water and blood. The blood-artificial surface interaction in BMHV is minimized. The contact between blood and BMHV surface is drastically reduced by polar-nonpolar Van der Waals forces. The "hydro/bloodphobia" of BMHV is intrinsically related to their chemical composition and their surface energy, thus their material: PyC indeed. Pertaining to thromboresistance, the surface roughness does not play a significant role. Instead, the thromboresistance of BMHV lies in molecular interactions. BMHV wettability can be tuned by altering the surface interface, by means of nanotechnology.


Asunto(s)
Prótesis Valvulares Cardíacas , Trombosis , Humectabilidad , Humanos , Trombosis/prevención & control , Diseño de Prótesis , Ensayo de Materiales
5.
BMC Biol ; 22(1): 115, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38764040

RESUMEN

BACKGROUND: Thromboinflammation is caused by mutual activation of platelets and neutrophils. The site of thromboinflammation is determined by chemoattracting agents release by endothelium, immune cells, and platelets. Impaired neutrophil chemotaxis contributes to the pathogenesis of Shwachman-Diamond syndrome (SDS). In this hereditary disorder, neutrophils are known to have aberrant chemoattractant-induced F-actin properties. Here, we aim to determine whether neutrophil chemotaxis could be analyzed using our previously developed ex vivo assay of the neutrophils crawling among the growing thrombi. METHODS: Adult and pediatric healthy donors, alongside with pediatric patients with SDS, were recruited for the study. Thrombus formation and granulocyte movement in hirudinated whole blood were visualized by fluorescent microscopy in fibrillar collagen-coated parallel-plate flow chambers. Alternatively, fibrinogen, fibronectin, vWF, or single tumor cells immobilized on coverslips were used. A computational model of chemokine distribution in flow chamber with a virtual neutrophil moving in it was used to analyze the observed data. RESULTS: The movement of healthy donor neutrophils predominantly occurred in the direction and vicinity of thrombi grown on collagen or around tumor cells. For SDS patients or on coatings other than collagen, the movement was characterized by randomness and significantly reduced velocities. Increase in wall shear rates to 300-500 1/s led to an increase in the proportion of rolling neutrophils. A stochastic algorithm simulating leucocyte chemotaxis movement in the calculated chemoattractant field could reproduce the experimental trajectories of moving neutrophils for 72% of cells. CONCLUSIONS: In samples from healthy donors, but not SDS patients, neutrophils move in the direction of large, chemoattractant-releasing platelet thrombi growing on collagen.


Asunto(s)
Neutrófilos , Trombosis , Humanos , Neutrófilos/fisiología , Trombosis/fisiopatología , Quimiotaxis , Adulto , Niño , Masculino , Quimiotaxis de Leucocito , Femenino , Movimiento Celular
6.
Sci Rep ; 14(1): 11460, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769378

RESUMEN

Arterial occlusion by thrombosis is the immediate cause of some strokes, heart attacks, and peripheral artery disease. Most prior studies assume that coagulation creates the thrombus. However, a contradiction arises as whole blood (WB) clots from coagulation are too weak to stop arterial blood pressures (> 150 mmHg). We measure the material mechanical properties of elasticity and ultimate strength for Shear-Induced Platelet Aggregation (SIPA) type clots, that form under stenotic arterial hemodynamics in comparison with coagulation clots. The ultimate strength of SIPA clots averaged 4.6 ± 1.3 kPa, while WB coagulation clots had a strength of 0.63 ± 0.3 kPa (p < 0.05). The elastic modulus of SIPA clots was 3.8 ± 1.5 kPa at 1 Hz and 0.5 mm displacement, or 2.8 times higher than WB coagulation clots (1.3 ± 1.2 kPa, p < 0.0001). This study shows that the SIPA thrombi, formed quickly under high shear hemodynamics, is seven-fold stronger and three-fold stiffer compared to WB coagulation clots. A force balance calculation shows a SIPA clot has the strength to resist arterial pressure with a short length of less than 2 mm, consistent with coronary pathology.


Asunto(s)
Coagulación Sanguínea , Agregación Plaquetaria , Trombosis , Humanos , Trombosis/patología , Resistencia al Corte , Hemodinámica , Módulo de Elasticidad , Plaquetas/metabolismo , Estrés Mecánico
7.
Clin Transl Sci ; 17(5): e13823, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38771157

RESUMEN

This study aims to investigate the mechanism of platelet activation-induced thrombosis in patients with acute non-ST segment elevation myocardial infarction (NSTEMI) by detecting the expression of autophagy-associated proteins in platelets of patients with NSTEMI. A prospective study was conducted on 121 patients with NSTEMI who underwent emergency coronary angiography and optical coherence tomography. The participants were divided into two groups: the ST segment un-offset group (n = 64) and the ST segment depression group (n = 57). We selected a control group of 60 patients without AMI during the same period. The levels of autophagy-associated proteins and the expression of autophagy-associated proteins in platelets were measured using immunofluorescence staining and Western blot. In NSTEMI, the prevalence of red thrombus was higher in the ST segment un-offset myocardial infarction (STUMI) group, whereas white thrombus was more common in the ST segment depression myocardial infarction (STDMI) group. Furthermore, the platelet aggregation rate was significantly higher in the white thrombus group compared with the red thrombus group. Compared with the control group, the autophagy-related protein expression decreased, and the expression of αIIbß3 increased in NSTEMI. The overexpression of Beclin1 could activate platelet autophagy and inhibit the expression of αIIbß3. The results suggested that the increase in platelet aggregation rate in patients with NSTEMI may be potentially related to the change in autophagy. And the overexpression of Beclin1 could reduce the platelet aggregation rate by activating platelet autophagy. Our findings demonstrated that Beclin1 could be a potential therapeutic target for inhibiting platelet aggregation in NSTEMI.


Asunto(s)
Autofagia , Beclina-1 , Plaquetas , Infarto del Miocardio sin Elevación del ST , Activación Plaquetaria , Trombosis , Humanos , Beclina-1/metabolismo , Masculino , Femenino , Infarto del Miocardio sin Elevación del ST/sangre , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Plaquetas/metabolismo , Trombosis/sangre , Trombosis/metabolismo , Angiografía Coronaria , Agregación Plaquetaria , Estudios de Casos y Controles , Tomografía de Coherencia Óptica , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo
8.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732160

RESUMEN

Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/virología , COVID-19/patología , SARS-CoV-2/patogenicidad , Pulmón/irrigación sanguínea , Pulmón/patología , Pulmón/virología , Embolia Pulmonar/virología , Embolia Pulmonar/etiología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/virología , Hipertensión Pulmonar/patología , Síndrome Post Agudo de COVID-19 , Trombosis/virología , Trombosis/etiología , Trombosis/patología
9.
Int J Mol Sci ; 25(9)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38732176

RESUMEN

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.


Asunto(s)
Trombocitopenia , Trombosis , Humanos , Trombocitopenia/diagnóstico , Trombosis/etiología , Plaquetas/metabolismo , Recuento de Plaquetas , Heparina/uso terapéutico , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/sangre
10.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38728442

RESUMEN

CASE: A 71-year-old woman presented with post-traumatic arthritis 11 months after open reduction and internal fixation for a left proximal humerus fracture (PHF) dislocation. After revision to reverse total shoulder arthroplasty (rTSA), the patient's left upper extremity was found to be avascular. An emergent thrombectomy was performed with restoration of arterial flow after removal of an acute-on-chronic axillary artery thrombus. CONCLUSION: Although rare, as rTSA becomes more common for management of PHF, incidence of associated vascular injuries is likely to rise. Screening methods and clinical vigilance in diagnosis are advised for patients with anterior PHF dislocations and arterial injury risk factors.


Asunto(s)
Artroplastía de Reemplazo de Hombro , Arteria Axilar , Fracturas del Hombro , Trombosis , Humanos , Femenino , Anciano , Arteria Axilar/cirugía , Arteria Axilar/lesiones , Arteria Axilar/diagnóstico por imagen , Fracturas del Hombro/cirugía , Fracturas del Hombro/diagnóstico por imagen , Artroplastía de Reemplazo de Hombro/efectos adversos , Trombosis/etiología , Trombosis/diagnóstico por imagen , Trombosis/cirugía , Fijación Interna de Fracturas/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Reducción Abierta/efectos adversos , Reoperación
11.
J Med Case Rep ; 18(1): 243, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38730499

RESUMEN

BACKGROUND: An ascending aortic thrombus is exceedingly rare. Two instances have been reported in the setting of lung cancer, but only after cisplatin use, which is associated with hypercoagulability. We present the first case of a patient with lung cancer who developed an ascending aortic thrombus without structural risk factors or chemotherapy use. CASE: A 60-year-old white female with significant smoking history presented with several weeks of malaise. A chest computed tomography scan revealed a 2.2-cm right upper lobe mass. As an outpatient, right hilar lymph node immunohistochemistry (IHC) samples via endobronchial ultrasound confirmed thyroid transcription factor-1 adenocarcinoma. After the procedure, the patient endorsed dyspnea and was advised to go to the emergency department. A chest computed tomography angiography identified a new 2.4 × 1.1 × 1.1 cm thrombus within the proximal aortic arch. No pulmonary emboli or intrapulmonary shunts were identified. A hypercoagulable workup was negative. Transthoracic echocardiogram was without left ventricular thrombus, akinesis or hypokinesis, left atrial dilation, or intracardiac shunts. A lower extremity ultrasound was negative for deep vein thrombosis. Given the procedural risk, thrombectomy was deferred. The patient was transitioned to enoxaparin, and a repeat computed tomography for resolution is in process. CONCLUSION: To our knowledge, this is the only case detailing an in situ ascending aortic thrombus in the setting of lung cancer, without structural risk factors, chemotherapy use, or other hypercoagulable comorbidities. Optimal management for an aortic thrombus and malignant disease is less clear. Clinicians should be vigilant for unusual arterial thromboses in patients with high metastatic burden.


Asunto(s)
Adenocarcinoma del Pulmón , Cisplatino , Neoplasias Pulmonares , Trombosis , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Cisplatino/uso terapéutico , Trombosis/diagnóstico por imagen , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/secundario , Adenocarcinoma del Pulmón/complicaciones , Enfermedades de la Aorta/diagnóstico por imagen , Anticoagulantes/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/complicaciones , Enoxaparina/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Angiografía por Tomografía Computarizada , Aorta/diagnóstico por imagen , Aorta/patología
12.
Pharmacol Res Perspect ; 12(3): e1201, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38775298

RESUMEN

The toxicity of inhaled particulate air pollution perseveres even at lower concentrations than those of the existing air quality limit. Therefore, the identification of safe and effective measures against pollutant particles-induced vascular toxicity is warranted. Carnosol is a bioactive phenolic diterpene found in rosemary herb, with anti-inflammatory and antioxidant actions. However, its possible protective effect on the thrombotic and vascular injury induced by diesel exhaust particles (DEP) has not been studied before. We assessed here the potential alleviating effect of carnosol (20 mg/kg) administered intraperitoneally 1 h before intratracheal (i.t.) instillation of DEP (20 µg/mouse). Twenty-four hours after the administration of DEP, various parameters were assessed. Carnosol administration prevented the increase in the plasma concentrations of C-reactive protein, fibrinogen, and tissue factor induced by DEP exposure. Carnosol inhibited DEP-induced prothrombotic effects in pial microvessels in vivo and platelet aggregation in vitro. The shortening of activated partial thromboplastin time and prothrombin time induced by DEP was abated by carnosol administration. Carnosol inhibited the increase in pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor α) and adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin) in aortic tissue. Moreover, it averted the effects of DEP-induced increase of thiobarbituric acid reactive substances, depletion of antioxidants and DNA damage in the aortic tissue. Likewise, carnosol prevented the decrease in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) caused by DEP. We conclude that carnosol alleviates DEP-induced thrombogenicity and vascular inflammation, oxidative damage, and DNA injury through Nrf2 and HO-1 activation.


Asunto(s)
Abietanos , Trombosis , Emisiones de Vehículos , Animales , Abietanos/farmacología , Ratones , Masculino , Emisiones de Vehículos/toxicidad , Trombosis/prevención & control , Trombosis/tratamiento farmacológico , Trombosis/inducido químicamente , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Lesiones del Sistema Vascular/tratamiento farmacológico , Antioxidantes/farmacología , Material Particulado/toxicidad , Material Particulado/efectos adversos , Factor 2 Relacionado con NF-E2/metabolismo , Contaminantes Atmosféricos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos
13.
Europace ; 26(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38691672

RESUMEN

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.


Asunto(s)
Anticoagulantes , Apéndice Atrial , Fibrilación Atrial , Ecocardiografía Transesofágica , Trombosis , Humanos , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/complicaciones , Masculino , Femenino , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/fisiopatología , Anciano , Trombosis/fisiopatología , Trombosis/diagnóstico por imagen , Trombosis/complicaciones , Persona de Mediana Edad , Velocidad del Flujo Sanguíneo , Anticoagulantes/uso terapéutico , Factores de Riesgo , Resultado del Tratamiento , Enfermedades Asintomáticas , Factores de Tiempo , Cardiopatías/fisiopatología , Cardiopatías/complicaciones , Cardiopatías/diagnóstico por imagen , Tromboembolia/etiología , Tromboembolia/fisiopatología , Anciano de 80 o más Años , Función del Atrio Izquierdo
14.
Clin Exp Med ; 24(1): 107, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776019

RESUMEN

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.


Asunto(s)
Proteínas de Fusión bcr-abl , Trastornos Mieloproliferativos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Trastornos Mieloproliferativos/sangre , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/diagnóstico , Proteínas de Fusión bcr-abl/genética , Trombomodulina/sangre , Fibrinolisina/metabolismo , Fibrinolisina/análisis , Anciano de 80 o más Años , Biomarcadores/sangre , Antitrombina III/genética , Trombosis , Hemorragia , Relevancia Clínica , alfa 2-Antiplasmina , Péptido Hidrolasas
17.
Thromb Res ; 238: 88-96, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38696925

RESUMEN

INTRODUCTION: Recommendations about proper anticoagulation in obese patients, body mass index (BMI) > 30 kg/m2, are not yet clearly defined. Obese patients were included in randomized controlled trials comparing new anticoagulants (NOACs) with warfarin in patients with atrial fibrillation or thromboembolism. METHODS: We performed a medline search entering proper criteria and finally 6 post-hoc analysis of RCTs, reporting outcome according to BMI, were included in this meta-analysis. Two major outcomes were considered end points in our meta-analysis; thrombosis, including ischemic cerebral events (transient or not) and venous thrombosis (DVD) /pulmonary embolism (PE) and bleeding, including major bleeding and clinically relevant non-major bleeding. RESULTS: In the NOACs treated group, thrombosis occurred less frequently in obese vs non-obese patients; RR and 95 % CI 0,75 (0,58-0,97), p = 0,03, while low heterogeneity was observed (I2= 40 %). In the warfarin treated subgroup there was statistically significant difference with less thrombotic events occurring in the obese vs non-obese patients; RR and (95 % CI) 0,80 (0,66-0,98), p = 0,03, and heterogeneity was low (I2 = 24 %). This protective effect called the obesity paradox is limited to obese patients anticoagulated for non-valvular atrial fibrillation (NVAF); RR (95 % CI) was 0,70 (0,58-0,85) p = 0,03 and I2 = 24 %. Bleeding events were similar under both NOACs and warfarin in obese vs non-obese analysis. CONCLUSIONS: Obese patients anticoagulated for NVAF with either standard dose of xabans or INR guided warfarin are more efficiently protected against thrombosis compared to non-obese patients.


Asunto(s)
Anticoagulantes , Fibrilación Atrial , Obesidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombosis , Warfarina , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Warfarina/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Trombosis/prevención & control , Trombosis/etiología , Hemorragia/inducido químicamente , Inhibidores del Factor Xa/uso terapéutico
18.
J Emerg Med ; 66(5): e614-e618, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38702244

RESUMEN

BACKGROUND: Left-sided intracardiac thrombi are most commonly seen in conditions with decreased cardiac flow, such as myocardial infarction or atrial fibrillation. They can be propagated into the systemic circulation, leading to a cerebrovascular accident. Identification of thrombus-in-transit via point-of-care ultrasound (POCUS) has the potential to change patient management given its association with high patient morbidity and mortality. CASE REPORT: An intubated 60-year-old man was transferred to our emergency department for management of altered mental status and seizure-like activity. The patient was markedly hypotensive on arrival, and cardiac POCUS was performed to identify potential causes of hypotension. A left ventricular thrombus-in-transit was identified. The thrombus was notably absent on a repeat POCUS examination < 10 min later, which led to concern for thrombus propagation. Furthermore, the patient's vasopressor requirements had significantly increased in that time period. Subsequent emergent neuroimaging revealed a large ischemic stroke in the left internal carotid and middle cerebral artery distribution. The patient was, unfortunately, deemed to not be a candidate for either thrombectomy or thrombolysis and ultimately expired in the hospital. Why Should an Emergency Physician Be Aware of This? Serial POCUS examinations identified the propagation of this patient's thrombus-in-transit, leading the physician to change the initial presumptive diagnosis and treatment course, and pursue further imaging and workup for ischemic stroke. Identification of a thrombus-in-transit is a clue to potentially underlying critical pathology and should be followed with serial POCUS examinations to assess for treatment efficacy and thrombus propagation.


Asunto(s)
Sistemas de Atención de Punto , Trombosis , Ultrasonografía , Humanos , Masculino , Persona de Mediana Edad , Trombosis/diagnóstico por imagen , Ultrasonografía/métodos , Servicio de Urgencia en Hospital/organización & administración , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Hipotensión/etiología , Cardiopatías/diagnóstico , Cardiopatías/complicaciones , Resultado Fatal
19.
Thromb Res ; 238: 117-128, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703585

RESUMEN

Previous research has identified intravascular platelet thrombi in regions affected by myocardial ischemia-reperfusion (MI/R) injury and neighbouring areas. However, the occurrence of arterial thrombosis in the context of MI/R injury remains unexplored. This study utilizes intravital microscopy to investigate carotid artery thrombosis during MI/R injury in rats, establishing a connection with the presence of prothrombotic cellular fibronectin containing extra domain A (CFN-EDA) protein. Additionally, the study examines samples from patients with coronary artery disease (CAD) both before and after coronary artery bypass grafting (CABG). Levels of CFN-EDA significantly increase following MI with further elevation observed following reperfusion of the ischemic myocardium. Thrombotic events, such as thrombus formation and growth, show a significant increase, while the time to complete cessation of blood flow in the carotid artery significantly decreases following MI/R injury induced by ferric chloride. The acute infusion of purified CFN-EDA protein accelerates in-vivo thrombotic events in healthy rats and significantly enhances in-vitro adenosine diphosphate and collagen-induced platelet aggregation. Treatment with anti-CFN-EDA antibodies protected the rat against MI/R injury and significantly improved cardiac function as evidenced by increased end-systolic pressure-volume relationship slope and preload recruitable stroke work compared to control. Similarly, in a human study, plasma CFN-EDA levels were notably elevated in CAD patients undergoing CABG. Post-surgery, these levels continued to rise over time, alongside cardiac injury biomarkers such as cardiac troponin and B-type natriuretic peptide. The study highlights that increased CFN-EDA due to CAD or MI initiates a destructive positive feedback loop by amplifying arterial thrombus formation, potentially exacerbating MI/R injury.


Asunto(s)
Fibronectinas , Daño por Reperfusión Miocárdica , Trombosis , Animales , Daño por Reperfusión Miocárdica/patología , Ratas , Humanos , Masculino , Trombosis/etiología , Trombosis/sangre , Trombosis/patología , Fibronectinas/metabolismo , Ratas Sprague-Dawley , Femenino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/sangre , Anciano
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