RESUMEN
BACKGROUND: Current coronavirus disease 2019 (COVID-19) pandemic reveals thrombotic, vascular, and endothelial dysfunctions at peak disease. However, the duration, degree of damage, and appropriate long-term use of antithrombotic strategies are unclear. Most COVID data are yielded from random clinical observations or autopsy of postmortem samples, while precise blood cellular data in survivors are insufficient. METHODS: We analyzed erythrocytes, circulating endothelial cells, and echinocytes by electron microscopy and flow cytometry in patients with confirmed COVID-19 (n = 31) and matched healthy controls (n = 32) on admission and at hospital discharge. RESULTS: All patients experienced mild disease, none required pulmonary support, and all survived. Admission number of circulating endothelial cells was significantly (40-100 times) higher in COVID-19 patients. Cells were massively damaged by multiple fenestrae in membranes with diameter comparable to the size of supercapsid in SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus. COVID-19 also provoked formation of stacked aggregated erythrocytes capable of clogging microvascular bed and of diminishing oxygen supply. In some patients, such abnormalities persisted at hospital discharge revealing remaining intracellular penetration of SARS-CoV-2 where it may be replicated and returned to circulation. CONCLUSION: These observational and descriptive data suggest that persistent viral cell injury may cause blood vessel damage; their increased permeability resulted in tissue edema, inflammation, platelet activation, and augmented thrombosis. There is a residual blood cell damage following the acute phase in some COVID-19 survivors. Controlled outcome-driven trials are urgently needed for exploring optimal use of long-term antithrombotics and vascular protection strategies even after mild COVID-19.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19/sangre , Fibrinolíticos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Células Endoteliales/efectos de los fármacos , Células Endoteliales/ultraestructura , Eritrocitos/efectos de los fármacos , Eritrocitos/ultraestructura , Eritrocitos Anormales/efectos de los fármacos , Eritrocitos Anormales/ultraestructura , Femenino , Humanos , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Pandemias , Estudios Prospectivos , SARS-CoV-2Asunto(s)
Anemia Hemolítica/sangre , Eritrocitos Anormales/ultraestructura , Hemoglobinopatías/sangre , Hemoglobinas Anormales/genética , Insuficiencia Multiorgánica/sangre , Esfuerzo Físico , Anemia Hemolítica/etiología , Anemia Hemolítica/genética , Anemia Hemolítica/terapia , Autoanticuerpos/inmunología , Núcleo Celular/ultraestructura , Deshidratación/sangre , Deshidratación/etiología , Inclusiones Eritrocíticas/ultraestructura , Transfusión de Eritrocitos , Resultado Fatal , Enfermedades de las Válvulas Cardíacas/complicaciones , Hemoglobinopatías/complicaciones , Hemoglobinopatías/genética , Humanos , Isoanticuerpos/inmunología , Masculino , Insuficiencia Multiorgánica/etiología , Choque Cardiogénico/etiologíaAsunto(s)
Anemia de Células Falciformes/complicaciones , Médula Ósea/irrigación sanguínea , Muerte Súbita/etiología , Paro Cardíaco/etiología , Infarto/etiología , Isquemia/etiología , Choque/etiología , Anemia de Células Falciformes/fisiopatología , Médula Ósea/patología , Errores Diagnósticos , Eritrocitos Anormales/ultraestructura , Femenino , Humanos , Infarto/fisiopatología , Isquemia/fisiopatología , Hígado/patología , Pulmón/patología , Embolia Pulmonar/diagnóstico , Choque/fisiopatología , Bazo/patología , Adulto JovenAsunto(s)
Anemia/sangre , Volumen de Eritrocitos , Compuestos Férricos/uso terapéutico , Maltosa/análogos & derivados , Anciano , Anemia/tratamiento farmacológico , Anemia/etiología , Eritrocitos Anormales/ultraestructura , Femenino , Compuestos Férricos/administración & dosificación , Hemorragia Gastrointestinal/complicaciones , Hemoglobinas/análisis , Hemorroides/complicaciones , Humanos , Infusiones Intravenosas , Leucovorina/uso terapéutico , Maltosa/administración & dosificación , Maltosa/uso terapéutico , Recto , Recuento de Reticulocitos , Vitamina B 12/uso terapéuticoAsunto(s)
Anemia Hemolítica Congénita no Esferocítica/fisiopatología , Hematopoyesis Extramedular , Piruvato Quinasa/deficiencia , Errores Innatos del Metabolismo del Piruvato/fisiopatología , Piel/fisiopatología , Anemia Hemolítica Congénita no Esferocítica/diagnóstico , Anemia Hemolítica Congénita no Esferocítica/genética , Eritrocitos Anormales/ultraestructura , Exantema/etiología , Exantema/patología , Femenino , Heterocigoto , Humanos , Hipoglucemia/congénito , Hipoglucemia/etiología , Hipoglucemia/genética , Hipoxia/etiología , Recién Nacido , Piruvato Quinasa/genética , Errores Innatos del Metabolismo del Piruvato/diagnóstico , Errores Innatos del Metabolismo del Piruvato/genéticaAsunto(s)
Anemia Hemolítica Congénita/diagnóstico , Procesamiento de Imagen Asistido por Computador/métodos , Análisis de la Célula Individual/métodos , Aprendizaje Automático Supervisado , Anemia Hemolítica Congénita/sangre , Anemia Hemolítica Congénita no Esferocítica/sangre , Anemia Hemolítica Congénita no Esferocítica/diagnóstico , Automatización , Viscosidad Sanguínea , Conjuntos de Datos como Asunto , Deformación Eritrocítica , Eritrocitos Anormales/ultraestructura , Humanos , Hidropesía Fetal/sangre , Hidropesía Fetal/diagnóstico , Procesamiento de Imagen Asistido por Computador/instrumentación , Piruvato Quinasa/sangre , Piruvato Quinasa/deficiencia , Errores Innatos del Metabolismo del Piruvato/sangre , Errores Innatos del Metabolismo del Piruvato/diagnóstico , Reticulocitos/ultraestructura , Análisis de la Célula Individual/instrumentaciónAsunto(s)
Infecciones por Coronavirus/sangre , Eritrocitos Anormales/ultraestructura , Monocitos/ultraestructura , Neumonía Viral/sangre , Anciano de 80 o más Años , Plaquetas/ultraestructura , COVID-19 , Comorbilidad , Resultado Fatal , Humanos , Masculino , Megacariocitos/ultraestructura , Pandemias , Vacuolas/ultraestructuraRESUMEN
OBJECTIVES: Myelodysplastic syndrome (MDS) is a highly mortal disease in which anemia is unresponsive to treatment. In this study, the effect of basal ferritin values on prognosis and survival was investigated in MDS patients without history of transfusion. METHODS: Data were retrospectively analyzed for 62 MDS cases. The cases were divided into two groups according to ferritin values. RESULTS: The mean survival time was 61.1±4.8 months. During the follow-up period, 34 (54.8%) patients deceased. Median ferritin level was 358ng/mL. The serum ferritin (SF) level associated with mortality was determined as 400ng/mL (ROC area for SF was 0.731 with a cutoff value of 400; sensitivity and specificity were 70.7% and 68.2%, respectively) (P=0.002). There were 29 (46.8%) patients with serum ferritin levels of ≥400ng/mL. Patients with serum ferritin levels≥400ng/mL had low survival rates. Ferritin≥400ng/mL was associated with six times increased mortality (P=0.001). CONCLUSION: Although the acceptable ferritin level at the start of chelation therapy is 1000ng/mL, the fact that 400ng/mL value is associated with survival in our study suggests that it may be useful to start chelation therapy in the early period. Further case studies on the subject are required.
Asunto(s)
Ferritinas/sangre , Síndromes Mielodisplásicos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Linaje de la Célula , Progresión de la Enfermedad , Eritrocitos Anormales/ultraestructura , Femenino , Fibrosis , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis de SupervivenciaRESUMEN
Abnormal red blood cell (RBC) adhesion to endothelial αvß3 plays a crucial role in triggering vaso-occlusive episodes in sickle cell disease (SCD). It is known that epinephrine, a ß-adrenergic receptor (ß-AR) stimulator, increases the RBC surface density of active intercellular adhesion molecule-4 (ICAM-4) which binds to the endothelial αvß3. It has also been demonstrated that in human embryonic kidney 293 cells, mouse cardiomyocytes, and COS-7 cell lines, the ß-adrenergic and renin-angiotensin systems are interrelated and that there is a direct interaction and cross-regulation between ß-AR and angiotensin II type 1 receptor (AT1R). Selective blockade of AT1R reciprocally inhibits the downstream signaling of ß-ARs, similar to the inhibition observed in the presence of a ß-AR-blocker. However, it is not known if this mechanism is active in human RBCs. Here, we studied the effect of valsartan, an AT1R blocker, on the surface density of active ICAM-4 receptors in normal, sickle cell trait, and homozygous sickle RBCs. We applied single molecule force spectroscopy to detect active ICAM-4 receptors on the RBC plasma membrane with and without the presence of valsartan and epinephrine. We found that epinephrine significantly increased whereas valsartan decreased their surface density. Importantly, we found that pretreatment of RBCs with valsartan significantly impeded the activation of ICAM-4 receptors induced by epinephrine. The observed reduced expression of active ICAM-4 receptors on the RBC plasma membrane leads us to conjecture that valsartan may be used as a supporting remedy for the prevention and treatment of vaso-occlusive crisis in SCD.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Epinefrina/farmacología , Membrana Eritrocítica/metabolismo , Eritrocitos Anormales/metabolismo , Rasgo Drepanocítico/metabolismo , Valsartán/farmacología , Adolescente , Adulto , Animales , Células COS , Chlorocebus aethiops , Membrana Eritrocítica/ultraestructura , Eritrocitos Anormales/ultraestructura , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Microscopía de Fuerza Atómica , Receptor de Angiotensina Tipo 1/metabolismo , Rasgo Drepanocítico/patologíaRESUMEN
AIMS: Iron overload is a major factor contributing to the overall pathology of thalassaemia, which is primarily mediated by ineffective erythropoiesis and shorter mature red blood cell (RBC) survival. Iron accumulation in RBCs generates reactive oxygen species (ROS) that cause cellular damage such as lipid peroxidation and RBC membrane deformation. Abnormal RBCs in patients with thalassaemia are commonly known as microcytic hypochromic anaemia with poikilocytosis. However, iron and ROS accumulation in RBCs as related to RBC morphological changes in patients with thalassaemia has not been reported. METHODS: Twenty-one patients with thalassaemia, including HbH, HbH with Hb Constant Spring and ß-thalassaemia/HbE (splenectomy and non-splenectomy) genotypes, and five normal subjects were recruited. RBC morphology was analysed by light and scanning electron microscopy. Systemic and RBC iron status and oxidative stress were examined. RESULTS: Decreased normocytes were observed in the samples of patients with thalassaemia, with RBC morphological abnormality being related to the type of disease (α-thalassaemia or ß-thalassaemia) and splenic status. Target cells and crenated cells were mainly found in splenectomised patients with ß-thalassaemia/HbE, while target cells and teardrop cells were found in non-splenectomised patients. Patients with thalassaemia had high levels of serum ferritin, red cell ferritin and ROS in RBCs compared with normal subjects (p<0.05). Negative correlations between the amount of normocytes and serum ferritin (rs=-0.518, p=0.011), red cell ferritin (rs=-0.467, p=0.025) or ROS in RBCs (rs=-0.672, p<0.001) were observed. CONCLUSIONS: Iron overload and its consequent intracellular oxidative stress in RBCs were associated with reduce normocytes in patients with thalassaemia.
Asunto(s)
Eritrocitos Anormales/ultraestructura , Sobrecarga de Hierro/patología , Hierro/sangre , Estrés Oxidativo , Talasemia/patología , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Eritrocitos Anormales/metabolismo , Femenino , Ferritinas/sangre , Humanos , Sobrecarga de Hierro/sangre , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Especies Reactivas de Oxígeno/sangre , Talasemia/sangre , Adulto JovenRESUMEN
An improved red blood cell (RBC) membrane model is developed based on the bilayer coupling model (BCM) to accurately predict the complete sequence of stomatocyte-discocyte-echinocyte (SDE) transformation of a RBC. The coarse-grained (CG)-RBC membrane model is proposed to predict the minimum energy configuration of the RBC from the competition between lipid-bilayer bending resistance and cytoskeletal shear resistance under given reference constraints. In addition to the conventional membrane surface area, cell volume and bilayer-leaflet-area-difference constraints, a new constraint: total-membrane-curvature is proposed in the model to better predict RBC shapes in agreement with experimental observations. A quantitative evaluation of several cellular measurements including length, thickness and shape factor, is performed for the first time, between CG-RBC model predicted and three-dimensional (3D) confocal microscopy imaging generated RBC shapes at equivalent reference constraints. The validated CG-RBC membrane model is then employed to investigate the effect of reduced cell volume and elastic length scale on SDE transformation, to evaluate the RBC deformability during SDE transformation, and to identify the most probable RBC cytoskeletal reference state. The CG-RBC membrane model can predict the SDE shape behaviour under diverse shape-transforming scenarios, in-vitro RBC storage, microvascular circulation and flow through microfluidic devices.
Asunto(s)
Algoritmos , Deformación Eritrocítica , Membrana Eritrocítica/metabolismo , Eritrocitos Anormales/metabolismo , Eritrocitos/metabolismo , Modelos Biológicos , Fenómenos Biomecánicos , Tamaño de la Célula , Membrana Eritrocítica/ultraestructura , Eritrocitos/ultraestructura , Eritrocitos Anormales/ultraestructura , Humanos , Microscopía Electrónica de RastreoAsunto(s)
Anemia Hemolítica Congénita/sangre , Eritrocitos Anormales/ultraestructura , Cuerpos de Heinz/ultraestructura , Estrés Oxidativo , Anemia Hemolítica Congénita/patología , Anemia Hemolítica Congénita/terapia , Enfermedades en Gemelos/sangre , Transfusión de Eritrocitos , Femenino , Cuerpos de Heinz/patología , Humanos , Recién Nacido , Ictericia Neonatal/etiología , Gemelos DicigóticosAsunto(s)
Anemia de Células Falciformes/terapia , Trasplante de Médula Ósea/efectos adversos , Síndrome de Activación Macrofágica/etiología , Microangiopatías Trombóticas/etiología , Adolescente , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Citocinas/uso terapéutico , Eritrocitos Anormales/ultraestructura , Neutropenia Febril/inducido químicamente , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Herpesvirus Humano 6/aislamiento & purificación , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Células Madre Mesenquimatosas , Monocitos/ultraestructura , Intercambio Plasmático , Rituximab/uso terapéutico , Infecciones por Roseolovirus/complicaciones , Microangiopatías Trombóticas/sangre , Microangiopatías Trombóticas/inmunología , Microangiopatías Trombóticas/terapia , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
BACKGROUND: Previous investigations in leukoreduced units of red blood cells (RBCs) in mannitol additive solution revealed the close association of uric acid (UA) levels in vivo with the susceptibility of RBCs to storage lesion markers. In this study, we examined whether UA has a similar correlation with the capability of RBCs to cope with the oxidative provocations of storage under different conditions, namely, in CPDA-1 and in the absence of leukoreduction. STUDY DESIGN AND METHODS: The UA-dependent antioxidant capacity of the supernatant was measured in nonleukoreduced units of RBCs in CPDA (n = 47). The possible effect of UA variability on the storage lesion profile was assessed by monitoring several physiologic properties of RBCs and supernatant, including cell shape, reactive oxygen species, and size distribution of extracellular vesicles, in units exhibiting the lowest or highest levels of UA activity (n = 16) among donors, throughout the storage period. RESULTS: In stored RBC units, the UA-dependent antioxidant activity of the supernatant declined as a function of storage duration but always in strong relation to the UA levels in fresh blood. Contrary to units of poor-UA activity, RBCs with the highest levels of UA activity exhibited better profile of calcium- and oxidative stress-driven modifications, including a significant decrease in the percentages of spherocytes and of 100- to 300-nm-sized vesicles, typically associated with the exovesiculation of stored RBCs. CONCLUSION: The antioxidant activity of UA is associated with donor-specific differences in the performance of RBCs under storage in nonleukoreduced CPDA units.
Asunto(s)
Donantes de Sangre , Conservación de la Sangre/métodos , Eritrocitos/citología , Ácido Úrico/sangre , Adenina/farmacología , Adolescente , Adulto , Antioxidantes/análisis , Biomarcadores , Calcio/sangre , Citratos/farmacología , Dispersión Dinámica de Luz , Eritrocitos/efectos de los fármacos , Eritrocitos Anormales/ultraestructura , Vesículas Extracelulares/ultraestructura , Glucosa/farmacología , Hemólisis , Humanos , Masculino , Manitol/farmacología , Estrés Oxidativo , Fosfatos/farmacología , Especies Reactivas de Oxígeno , Adulto JovenRESUMEN
Mechanisms responsible for anemia in systemic lupus erythematosus (SLE) can be immune or non-immune. A 27-year-old previously healthy woman was admitted with echymotic patches over the lower limbs for six months, multiple joint pain and fatigue for 2 months. She had severe pallor and multiple echymotic patches over the lower limbs. She was diagnosed with SLE with pernicious anemia and iron deficiency anemia. The rare association of SLE with pernicious anemia was reported previously in few patients. Treatment of SLE along with B12 supplementation is necessary for such patients. Since etiology for anemia in SLE can be of various kinds, a detailed workup for identifying the underlying mechanism is necessary.
Asunto(s)
Anemia Perniciosa/etiología , Lupus Eritematoso Sistémico/sangre , Adulto , Anemia Ferropénica/etiología , Anemia Perniciosa/tratamiento farmacológico , Eritrocitos Anormales/ultraestructura , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Vitamina B 12/uso terapéuticoRESUMEN
The inflammatory burden of the complex rheumatoid arthritis (RA) disease affects several organ-systems, including rheological properties of blood and its formed elements. Red blood cells (RBCs) are constantly exposed to circulating dysregulated inflammatory molecules that are co-transported within the vasculature; and their membranes may be particularly vulnerable to the accompanying oxidative stress. In the current study, we investigate biophysical and ultrastructural characteristics of RBCs obtained from a cohort of patients using atomic force microscopy (AFM), scanning electron microscopy (SEM) and confocal microscopy (CM). Statistical analyses of AFM data showed that RA RBCs possessed significantly reduced membrane elasticity relative to that of RBCs from healthy individuals (P-value <0.0001). SEM imaging of RA RBCs revealed increased anisocytes and poikilocytes. Poikilocytes included knizocytes, stomatocytes, dacryocytes, irregularly contracted cells, and knot cells. CM imaging of several RA RBCs, spectrin, and band 3 protein networks portrayed the similar morphological profiles. Analyses of CM images confirmed changes to distribution of band-3 skeletal protein, a protein critical for gaseous exchange functions of the RBC and preventing membrane surface loss. Decreased membrane deformability impairs the RBC's capacity to adequately adapt its shape to navigate blood vessels, especially microvasculature, and this decrease is also reflected in the cell's morphology. Changes to morphology and deformability may also indicate loss of functional domains and/or pathological protein and lipid associations. These findings suggest that RA disease and/or its concomitant factors impact on the RBC and its membrane integrity with potential for exacerbating pathological cellular function, hemorheology, and cardiovascular function.
Asunto(s)
Artritis Reumatoide/sangre , Membrana Eritrocítica/ultraestructura , Eritrocitos Anormales/ultraestructura , Artritis Reumatoide/patología , Estudios de Casos y Controles , Módulo de Elasticidad , Deformación Eritrocítica , Membrana Eritrocítica/patología , Eritrocitos Anormales/patología , Humanos , Microscopía de Fuerza Atómica , Microscopía Electrónica de RastreoAsunto(s)
Eliptocitosis Hereditaria/sangre , Eritrocitos Anormales/ultraestructura , Rasgo Drepanocítico/sangre , Trombocitosis/sangre , Talasemia beta/sangre , Eliptocitosis Hereditaria/complicaciones , Eliptocitosis Hereditaria/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Rasgo Drepanocítico/complicaciones , Trombocitosis/complicaciones , Talasemia beta/complicacionesAsunto(s)
Anemia de Células Falciformes/sangre , Eritrocitos Anormales/ultraestructura , Hipoxia/sangre , Anemia de Células Falciformes/complicaciones , Progresión de la Enfermedad , Membrana Eritrocítica/ultraestructura , Femenino , Paro Cardíaco/sangre , Paro Cardíaco/etiología , Hemoglobinas/análisis , Humanos , Hipoxia/etiología , Masculino , Persona de Mediana Edad , Rasgo Drepanocítico/sangre , Adulto Joven , Talasemia beta/sangreRESUMEN
Sickle cell disease (SCD) is caused by an inherited mutation in hemoglobin that leads to sickle hemoglobin (HbS) polymerization and premature HbS denaturation. Previous publications have shown that HbS denaturation is followed by binding of denatured HbS (a.k.a. hemichromes) to band 3, the consequent clustering of band 3 in the plane of the erythrocyte membrane that in turn promotes binding of autologous antibodies to the clustered band 3, and removal of the antibody-coated erythrocytes from circulation. Although each step of the above process has been individually demonstrated, the fraction of band 3 that is altered by association with denatured HbS has never been determined. For this purpose, we evaluated the lateral diffusion of band 3 in normal cells, reversibly sickled cells (RSC), irreversibly sickled cells (ISC), and hemoglobin SC erythrocytes (HbSC) in order to estimate the fraction of band 3 that was diffusing more slowly due to hemichrome-induced clustering. We labeled fewer than ten band 3 molecules per intact erythrocyte with a quantum dot to avoid perturbing membrane structure and we then monitored band 3 lateral diffusion by single particle tracking. We report here that the size of the slowly diffusing population of band 3 increases in the sequence: normal cellsAsunto(s)
Anemia de Células Falciformes/sangre
, Proteína 1 de Intercambio de Anión de Eritrocito/química
, Membrana Eritrocítica/química
, Hemoproteínas/química
, Anemia de Células Falciformes/patología
, Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo
, Células Cultivadas
, Difusión
, Membrana Eritrocítica/metabolismo
, Membrana Eritrocítica/ultraestructura
, Eritrocitos Anormales/química
, Eritrocitos Anormales/metabolismo
, Eritrocitos Anormales/ultraestructura
, Hemoproteínas/metabolismo
, Hemoglobina Falciforme/química
, Hemoglobina Falciforme/metabolismo
, Humanos
, Sondas Moleculares/química
, Puntos Cuánticos/química
, Imagen Individual de Molécula/métodos
, Coloración y Etiquetado/métodos