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1.
Br J Haematol ; 195(4): 629-633, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34396507

RESUMO

The present study tested the impact of α-thalassaemia on oxygen gradient ektacytometry in sickle cell anaemia (SCA). Three SCA groups were compared: (i) no α-thalassaemia (four α-genes, n = 62), (ii) silent α-thalassaemia (three α-genes, n = 35) and (iii) homozygous α-thalassaemia (two α-genes, n = 12). Red blood cell (RBC) deformability measured in normoxia was not different between the three groups. The lowest RBC deformability reached at low oxygen partial pressure (pO2 ) was greater and the pO2 at which RBC started to sickle was lower in the two α-genes group compared to the other groups. Our present study showed an effect of α-thalassaemia on oxygen gradient ektacytometry in SCA.


Assuntos
Anemia Falciforme/sangue , Deformação Eritrocítica , Oxigênio/sangue , Talassemia alfa/sangue , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/genética , Criança , Pré-Escolar , Índices de Eritrócitos , Genótipo , Humanos , Pressão Osmótica , Resistência ao Cisalhamento , Adulto Jovem , alfa-Globinas/genética , Talassemia alfa/complicações , Talassemia alfa/genética , Globinas beta/genética
2.
Transfus Apher Sci ; 58(2): 128-131, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30879904

RESUMO

Sickle cell disease (SCD) is a genetic disorder characterised by a single mutation of the beta globin gene, causing the production of an abnormal haemoglobin called sickle haemoglobin (HbS). In its deoxygenated form, HbS polymerises, causing major rheological disorders, which presents clinically as periodic vaso-occlusive crises, chronic haemolysis and chronic vascular dysfunction. Patients often resort to a background treatment, and transfusion remains the cornerstone in the management of the disease, significantly reducing morbidity and mortality. The aim of red blood cell exchange (RBCX) is to improve tissue oxygenation by increasing haemoglobin levels while lowering HbS levels. RBCX can be performed by manual or automated exchange, and each technique has its own set of advantages and disadvantages. This article will outline the transfusion indications for the main complications of SCD, as well as the most appropriate strategy to use.


Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/terapia , Transfusão de Eritrócitos/métodos , Anemia Falciforme/patologia , Humanos
3.
Crit Care Med ; 46(2): e166-e169, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29206764

RESUMO

OBJECTIVE: Quick identification of septic source is fundamental in patients with severe sepsis of unknown origin. The purpose of this case report was to assess the benefit and feasibility of an early PET-CT in critically ill patients with undiagnosed sepsis. DATA SOURCES: Clinical observations of two patients. STUDY SELECTION: Case reports. DATA EXTRACTION: Data extracted from medical records, after patient's consent. Illustrations were collected from the imaging software. DATA SYNTHESIS: We admitted two critically ill patients for suspected sepsis and altered mental state. As all bacteriological samples were initially sterile, diagnostic workups in both patients led us to suspect underlying malignant hemopathy. In fact, the lumbar puncture of the first patient revealed a large B-cell lymphoma, and an acquired thrombotic thrombocytopenic purpura was suspected in the second patient. However, PET-CTs performed in both patients displayed infra-clinical underlying infectious foci. Within 48 hours, both patients developed a clearly identified sepsis linked to the described focus, and favorable outcome thanks to the precious information delivered by the PET-CT. CONCLUSIONS: PET-CT precisely detected the deep foci of infection about 48 hours prior to the diagnosis of sepsis. The cases reports suggested the use of this image technique in ICU for patients with sepsis of unknown origin.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sepse/diagnóstico por imagem , Idoso , Estado Terminal , Estudos de Viabilidade , Humanos , Masculino
4.
Nitric Oxide ; 81: 28-35, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30342855

RESUMO

Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.


Assuntos
Anemia Falciforme/tratamento farmacológico , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hidroxiureia/farmacologia , Nitritos/sangue , Adulto , Eritrócitos/fisiologia , Feminino , Humanos , Masculino , Óxido Nítrico/sangue , Óxido Nítrico Sintase/metabolismo , Nitroprussiato/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/sangue , Transdução de Sinais/efeitos dos fármacos
11.
Bone ; 178: 116924, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37783302

RESUMO

PURPOSE: Bone fragility in sickle cell disease (SCD) has been previously reported even in young patients, but the clinical consequences and specific management remain unclear. The objective of this study was to assess the prevalence of bone fragility in sickle cell patients and to evaluate the potential risk factors and associated complications. METHODS: We conducted a single-center cross-sectional study. Bone mineral densitometry (BMD) at the lumbar spine and the hip, Vertebral Fracture Assessment (VFA) and biological measurements were performed in patients aged between 20 and 40 years. RESULTS: One hundred and thirty-eight patients with sickle cell disease were included between June 2020 and December 2021. One hundred and one patients (73.2 %) were from Sub-Saharan Africa, 13 from North Africa (9.4 %), 11 from the Caribbean (7.9 %), 6 from the Indian Ocean. A Z-score < -2 was found in 43 patients (31.2 %) at the lumbar spine, in 4 patients (3 %) at the total hip, and in 5 patients (3.7 %) at the femoral neck. 59 patients (46.8 %) had vertebral deformities. Fragility fractures were recorded in 9 patients (10.8 %). Patients with low BMD had lower BMI (21.3 (19.0, 24.0) versus 24.0 (20.7, 26.1) Kg/m2, p = 0.003), lower osteonecrosis history (7 % versus 25.3 %, p = 0.011) and lower hemoglobin levels (9.0 (8.0, 10.0) versus 10.0 (9.0, 11.0) g/dL, p < 0.01). No association was found between history of fracture and low BMD. CONCLUSION: Young patients with SCD commonly have low BMD at the lumbar spine, but the prevalence of fragility fracture was low. Low BMD - specifically at the spine - may not be tantamount to bone fragility.


Assuntos
Anemia Falciforme , Doenças Ósseas Metabólicas , Fraturas Ósseas , Fraturas da Coluna Vertebral , Humanos , Adulto Jovem , Adulto , Densidade Óssea , Prevalência , Estudos Transversais , Absorciometria de Fóton/efeitos adversos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/complicações , Fraturas da Coluna Vertebral/epidemiologia , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia
12.
Blood Adv ; 8(2): 276-286, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-37976458

RESUMO

ABSTRACT: We investigated the potential of the point of sickling (PoS; the pO2 tension at which red cells start to sickle), determined by oxygen gradient ektacytometry to serve as a biomarker associated with the incidence of acute sickle cell disease-related complications in 177 children and 50 adults. In the pediatric cohort, for every 10 mmHg increase in PoS reflecting a greater likelihood of sickling, the likelihood of an individual experiencing >1 type of acute complication increased; the adjusted odds ratio (aOR) was 1.65. For every 0.1 increase in minimum elongation index (EImin; reflecting improved red blood cell deformability at hypoxia), the aOR was 0.50. In the adult cohort, for every 10 mmHg increase in PoS, we found an aOR of 3.00, although this was not significant after correcting for multiple testing. There was a trend for an association between higher PoS and greater likelihood of vaso-occlusive episodes (VOEs; children aOR, 1.35; adults aOR, 2.22). In children, only EImin was associated with VOEs (aOR, 0.68). When data of both cohorts were pooled, significant associations with PoS and/or EImin were found for all acute complications, independently and when >1 type of acute complication was assessed. These findings indicate that oxygen gradient ektacytometry generates novel biomarkers and provides a rationale for further development of these biomarkers in the assessment of clinical severity, evaluation of novel therapies, and as surrogate clinical trial end points. These biomarkers may be useful in assessing efficacy of novel therapies like pyruvate kinase activators, voxelotor, and L-glutamine.


Assuntos
Anemia Falciforme , Oxigênio , Adulto , Humanos , Criança , Oxigênio/metabolismo , Eritrócitos/metabolismo , Eritrócitos Anormais/metabolismo , Biomarcadores/metabolismo
13.
J Clin Med ; 12(4)2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36835792

RESUMO

BACKGROUND: Cerebral vasculopathy can induce chronic cerebral hypoperfusion leading to stroke in patients with sickle cell disease (SCD) and is treated by blood exchange transfusion (BET). However, no prospective clinical study has demonstrated the benefit of BET in adults with SCD and cerebral vasculopathy. Near Infrared Spectroscopy (NIRS) is a recent non-invasive method complementary to Magnetic Resonance Imaging (MRI). We evaluated cerebral perfusion using NIRS during erythracytapheresis in patients with SCD with and without steno-occlusive arterial disease. METHODS: We conducted a monocentric, prospective study in 16 adults with SCD undergoing erythracytapheresis in 2014. Among them, 10 had cerebral steno-occlusive arterial disease. NIRS measured the relative amounts of oxyhemoglobin (OxyHb), deoxyhemoglobin (DeoxyHb) and total hemoglobin (Total Hb) in brain tissue and in muscle. RESULTS: In cerebral hemispheres associated with steno-occlusive arterial disease, we observed a significant increase of OxyHb and Total Hb during BET, without modification of DeoxyHb. CONCLUSION: Using NIRS during BET showed that BET improves cerebral perfusion in adult patients with SCD with cerebral vasculopathy.

14.
Cells ; 11(3)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35159394

RESUMO

Oxygen gradient ektacytometry (oxygenscan) measures the changes in red blood cell (RBC) deformability in normoxia and during deoxygenation. We investigated the changes in RBC deformability, measured by both oxygenscan and classical shear-stress-gradient ektacytometry, in 10 patients with sickle cell disease (SCD) during vaso-occlusive crisis (VOC) versus steady state. Oxygenscan and shear-stress-gradient ektacytometry parameters were also measured in 38 SCD patients at steady state on two different occasions. Shear-stress-gradient ektacytometry parameters, maximal RBC deformability at normoxia and the minimum RBC deformability during deoxygenation were lower during VOC compared to steady state. The oxygen partial pressure at which RBCs started to sickle (PoS) was not significantly affected by VOC, but the results were very heterogeneous: the PoS increased in 5 in 10 patients and decreased in 4 in 10 patients. Both oxygenscan and shear-stress-gradient ektacytometry parameters remained unchanged in patients at steady state between two sets of measurements, performed at 17 ± 8 months intervals. In conclusion, the present study showed that both oxygen gradient ektacytometry and shear-stress-gradient ektacytometry are sensitive to disease activity in SCD, and that both techniques give comparable results; however, the oxygen-dependent propensity of RBCs to sickle was highly variable during VOC.


Assuntos
Anemia Falciforme , Deformação Eritrocítica , Eritrócitos , Humanos , Oxigênio
15.
Clin Hemorheol Microcirc ; 79(2): 357-361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057137

RESUMO

Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis and the presence of erythrocytes with low deformability, which may trigger vaso-occlusive crises. We tested the in-vitro effects of aqueous extract of chives (Allium schoenoprasum L.) on erythrocyte deformability of SCA patients. Blood samples from 6 apparently healthy volunteers and 5 SCA patients were collected into heparin coated tubes. Both apparently healthy and SCA patient blood samples were incubated with 80µg/mL chives plant aqueous extract at 37°C for 60 min and erythrocyte deformability was measured by ektacytometry (3 Pa and 30 Pa; 37°C). Results of incubation of apparently healthy blood samples with plant extract showed that incubation did not alter erythrocyte deformability significantly. However, for SCA blood samples, erythrocyte deformability decreased significantly with plant extract exposure at 3 Pa (p < 0.043) and 30 Pa (p < 0.043). In conclusion, although ex-vivo incubation with plant extract does not fully model gastrointestinal processing of onions, the decrease in SCA erythrocyte deformability following incubation with aqueous chives should stimulate further studies to test the in-vivo effects of this diet in sickle cell mice.


Assuntos
Anemia Falciforme , Cebolinha-Francesa , Anemia Falciforme/tratamento farmacológico , Animais , Deformação Eritrocítica , Eritrócitos , Eritrócitos Anormais , Humanos , Camundongos
16.
Front Physiol ; 12: 743399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630163

RESUMO

Background: Although obstructive sleep apnea (OSA) could act as a modulator of clinical severity in sickle cell disease (SCD), few studies focused on the associations between the two diseases. Research Question: The aims of this study were: (1) to explore the associations between OSA, nocturnal oxyhemoglobin saturation (SpO2) and the history of several acute/chronic complications, (2) to investigate the impact of OSA and nocturnal SpO2 on several biomarkers (hematological, blood rheological, and coagulation) in patients with SCD. Study Design and Methods: Forty-three homozygous SCD patients underwent a complete polysomnography recording followed by blood sampling. Results: The proportion of patients suffering from nocturnal hypoxemia did not differ between those with and those without OSA. No association between OSA and clinical severity was found. Nocturnal hypoxemia was associated with a higher proportion of patients with hemolytic complications (glomerulopathy, leg ulcer, priapism, or pulmonary hypertension). In addition, nocturnal hypoxemia was accompanied by a decrease in RBC deformability, enhanced hemolysis and more severe anemia. Interpretation: Nocturnal hypoxemia in SCD patients could be responsible for changes in RBC deformability resulting in enhanced hemolysis leading to the development of complications such as leg ulcers, priapism, pulmonary hypertension or glomerulopathy. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03753854.

17.
Clin Hemorheol Microcirc ; 77(4): 391-394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33361587

RESUMO

Sickle cell disease (SCD) is a genetic disorder characterized by the production of an abnormal hemoglobin (Hb), which, under deoxygenation, may polymerize and cause a mechanical distortion of red blood cell (RBC) into a crescent-like shape. Recently a method, using ektacytometry principle, has been developed to assess RBC deformability as a function of oxygen tension (pO2) and is called oxygen gradient ektacytometry (oxygenscan). However, standardization of this test is needed to properly assess the tendency of sickling of RBCs under deoxygenation and to allow comparisons between different laboratories. The study compared the oxygenscan responses during blood storage between distinct populations of SCD patients. Blood from 40 non-transfused homozygous SCD patients (HbSS), 16 chronically transfused HbSS patients, and 14 individuals with compound heterozygous hemoglobin SC disease (HbSC) at steady-state was collected in EDTA tubes. Measurements were performed within 4 hours after collection and after 24 hours of storage at 4°C. We showed that storage affected the minimum RBC deformability reached during deoxygenation (EImin) in both non-transfused HbSS and HbSC patients and the maximum RBC deformability (EImax) measured before deoxygenation (i.e., in normoxia) in the three groups. In contrast, the tendency of RBCs to sickle under deoxygenation (i.e., the point of sickling; PoS) remained rather stable between the two time of measurements. Collectively, since the time between blood sampling and analysis affects some key oxygen gradient ektacytometry-derived parameters we recommend that each laboratory performs oxygenscan measurements at a standardized time point.


Assuntos
Anemia Falciforme/sangue , Deformação Eritrocítica/genética , Oxigênio/metabolismo , Feminino , Humanos , Masculino
18.
Cells ; 10(4)2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33916502

RESUMO

(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/ß+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment.


Assuntos
Anemia Falciforme/genética , Anemia Falciforme/terapia , Oxigênio/metabolismo , Adulto , Anemia Falciforme/complicações , Agregação Celular , Pré-Escolar , Eritrócitos/patologia , Feminino , Genótipo , Hospitalização , Humanos , Masculino , Adulto Jovem
19.
Front Immunol ; 11: 551441, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250889

RESUMO

Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals. In-vitro experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA.


Assuntos
Anemia Falciforme/sangue , Micropartículas Derivadas de Células/metabolismo , Eriptose , Eritrócitos Anormais/metabolismo , Óxido Nítrico/sangue , Estresse Oxidativo , Rigidez Vascular , Adolescente , Adulto , Anemia Falciforme/patologia , Micropartículas Derivadas de Células/patologia , Criança , Pré-Escolar , Eritrócitos Anormais/patologia , Feminino , Humanos , Masculino
20.
Autoimmun Rev ; 18(2): 113-122, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572131

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD. METHODS: Studies were selected from MEDLINE up to July 2017. Two investigators independently extracted data on study design, patient characteristics, clinical features, treatment, follow-up and outcomes. Global survival rates and objectively confirmed lung function improvements were extracted as the main outcome for rapidly progressive IIM-related ILD (RP-ILD) and chronic forms of ILD (C-ILD), respectively, and pooled using the weighted mean proportion with fixed or random-effects models in case of significant heterogeneity (I2 > 50%). RESULTS: Twenty-seven studies encompassing 553 patients (male: 30.5%, age: 53.5 ±â€¯5.5 years) were included in the meta-analysis. Globally, retrieved studies were of limited methodological quality (no controlled studies and only 2 prospective studies). Dermatomyositis (40%) and anti-tRNA synthetase syndrome (45%) were the most represented IIM subtypes. In C-ILD, functional improvement rates were 89.2% (95%CI 82.5-93.6; 7 studies, n = 124) for corticosteroids alone, 80.7% (95%CI 49.6-94; 6 studies, n = 38) for cyclosporine A, 64.1% (95%CI 46.3-78.7; 4 studies, n = 32) for azathioprine, 86.2% (95%CI 61.5-96; 2 studies, n = 23) for tacrolimus, 56.4% (95%CI 44-68.0; 8 studies, n = 71) for cyclophosphamide, and 76.6% (95%CI 50.4-96.0; 2 studies, n = 20) for rituximab. In RP-ILD, survival rates at 3 months were 51.7% (95%CI 24.2-78.1; 2 studies, n = 11) for corticosteroids alone, 69.2% (95%CI 55.0-80.5; 8 studies, n = 146) for cyclosporine A and 72.4% (95%CI 6.4-99.0, 2 studies, n = 16) for cyclophosphamide. CONCLUSION: Despite aggressive immunosuppressive therapies, the short-term mortality of RP-ILD remains high. While immunosuppressive therapies are associated with significant functional improvements in most patients with C-ILD, substantial uncertainty remains about the best treatment strategy in the absence of good quality evidence.


Assuntos
Doenças Pulmonares Intersticiais/tratamento farmacológico , Miosite/tratamento farmacológico , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Miosite/etiologia , Miosite/patologia , Estudos Prospectivos
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