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Featured researches published by François Lionnet.


The New England Journal of Medicine | 2011

A Hemodynamic Study of Pulmonary Hypertension in Sickle Cell Disease

Florence Parent; Dora Bachir; Jocelyn Inamo; François Lionnet; Françoise Driss; Gylna Loko; Anoosha Habibi; Soumiya Bennani; Laurent Savale; Serge Adnot; Bernard Maitre; Azzedine Yaici; Leila Hajji; Dermot S. O'Callaghan; Pierre Clerson; Robert Girot; F. Galacteros; Gérald Simonneau

BACKGROUND The prevalence and characteristics of pulmonary hypertension in adults with sickle cell disease have not been clearly established. METHODS In this prospective study, we evaluated 398 outpatients with sickle cell disease (mean age, 34 years) at referral centers in France. All patients underwent Doppler echocardiography, with measurement of tricuspid-valve regurgitant jet velocity. Right heart catheterization was performed in 96 patients in whom pulmonary hypertension was suspected on the basis of a tricuspid regurgitant jet velocity of at least 2.5 m per second. Pulmonary hypertension was defined as a mean pulmonary arterial pressure of at least 25 mm Hg. RESULTS The prevalence of a tricuspid regurgitant jet velocity of at least 2.5 m per second was 27%. In contrast, the prevalence of pulmonary hypertension as confirmed on catheterization was 6%. The positive predictive value of echocardiography for the detection of pulmonary hypertension was 25%. Among the 24 patients with confirmed pulmonary hypertension, the pulmonary-capillary wedge pressure was 15 mm Hg or less (indicating precapillary pulmonary hypertension) in 11 patients. Patients with confirmed pulmonary hypertension were older and had poorer functional capacity and higher levels of N-terminal pro-brain natriuretic peptide than other patients. In contrast, patients who had a tricuspid regurgitant jet velocity of at least 2.5 m per second without pulmonary hypertension and patients with a tricuspid regurgitant jet velocity of less than 2.5 m per second had similar clinical characteristics. CONCLUSIONS In this study of adults with sickle cell disease, the prevalence of pulmonary hypertension as confirmed on right heart catheterization was 6%. Echocardiographic evaluation alone had a low positive predictive value for pulmonary hypertension. (Funded by the French Ministry of Health and Assistance Publique-Hôpitaux de Paris; ClinicalTrials.gov number, NCT00434902.).


Blood | 2015

Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease

Stéphane Camus; J. A. De Moraes; Philippe Bonnin; P. Abbyad; S. Le Jeune; François Lionnet; Laurent Loufrani; Linda Grimaud; J.-C. Lambry; Dominique Charue; Laurent Kiger; Jean-Marie Renard; C. Larroque; H. Le Clesiau; Alain Tedgui; Patrick Bruneval; Christina Barja-Fidalgo; A. Alexandrou; Pierre-Louis Tharaux; Chantal M. Boulanger; Olivier Blanc-Brude

Intravascular hemolysis describes the relocalization of heme and hemoglobin (Hb) from erythrocytes to plasma. We investigated the concept that erythrocyte membrane microparticles (MPs) concentrate cell-free heme in human hemolytic diseases, and that heme-laden MPs have a physiopathological impact. Up to one-third of cell-free heme in plasma from 47 patients with sickle cell disease (SCD) was sequestered in circulating MPs. Erythrocyte vesiculation in vitro produced MPs loaded with heme. In silico analysis predicted that externalized phosphatidylserine (PS) in MPs may associate with and help retain heme at the cell surface. Immunohistology identified Hb-laden MPs adherent to capillary endothelium in kidney biopsies from hyperalbuminuric SCD patients. In addition, heme-laden erythrocyte MPs adhered and transferred heme to cultured endothelial cells, inducing oxidative stress and apoptosis. In transgenic SAD mice, infusion of heme-laden MPs triggered rapid vasoocclusions in kidneys and compromised microvascular dilation ex vivo. These vascular effects were largely blocked by heme-scavenging hemopexin and by the PS antagonist annexin-a5, in vitro and in vivo. Adversely remodeled MPs carrying heme may thus be a source of oxidant stress for the endothelium, linking hemolysis to vascular injury. This pathway might provide new targets for the therapeutic preservation of vascular function in SCD.


Clinical Journal of The American Society of Nephrology | 2010

Glomerular hyperfiltration in adult sickle cell anemia: a frequent hemolysis associated feature.

Jean-Philippe Haymann; Katia Stankovic; Pierre Levy; Virginie Avellino; Pierre-Louis Tharaux; Emmanuel Letavernier; Gilles Grateau; Laurent Baud; Robert Girot; François Lionnet

BACKGROUND AND OBJECTIVES Sickle cell anemia-associated nephropathy is a growing matter of concern because renal failure affects most aging sickle cell anemia patients. Glomerular damage is a common feature revealed by a microalbuminuria or a macroalbuminuria. Although glomerular hyperfiltration has been described for decades in this population, its prevalence in young adults is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS To address this issue, as well as the clinical and biologic correlates of hyperfiltration, a single-center, cross-sectional study of 280 homozygous SS disease patients was performed. RESULTS The prevalence of hyperfiltration assessed by Modification of Diet in Renal Disease estimated GFR was 51%. Among patients with hyperfiltration, 49% had hyperfiltration alone, whereas 36% and 15% had an associated microalbuminuria or macroalbuminuria, respectively. Estimated GFR sensitivity and specificity for hyperfiltration were 94% and 63%, respectively, in a selected subgroup of 48 patients (measured GFR was assessed by urinary (51)Cr EDTA clearance). In patients with no albuminuria, hyperfiltration status was significantly associated with a young age (years), the absence of alpha thalassemia, a lower hemoglobin level (g/dl), and a lower fetal hemoglobin. The role of chronic hemolysis was further strengthened by multivariate analysis showing a correlation between estimated GFR and a low plasma fetal hemoglobin level, a young age, and a high reticulocyte count (r(2) = 0.54). CONCLUSIONS Together, the data suggest that the pathophysiology of hyperfiltration would rather be attributable to the hemolysis-associated vasculopathy rather than a viscosity-vaso-occlusive process.


Haematologica | 2012

Hemoglobin sickle cell disease complications: a clinical study of 179 cases.

François Lionnet; Nadjib Hammoudi; Katia Stankovic Stojanovic; Virginie Avellino; Gilles Grateau; Robert Girot; Jean-Philippe Haymann

Background Hemoglobin SC disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous SS disease. The aim of this study was to update our knowledge about hemoglobin SC disease. Design and Methods The study involved a single center series of 179 patients. Clinical and biological data were collected with special attention to the assessment of pulmonary arterial hypertension and nephropathy. Results Hemoglobin SC diagnosis was delayed and performed in adulthood in 29% of cases. Prevalence of hospitalized painful vasoocclusive crisis, acute chest syndrome and priapism was 36%, 20% and 20%, respectively. The most common chronic organ complications were retinopathy and sensorineural otological disorders in 70% and 29% of cases. Indeed, prevalence of complications reported in homozygous SS disease, such as nephropathy, suspicion of pulmonary hypertension, strokes and leg ulcers was rather low (13%, 4% and 1%, respectively). Phlebotomy performed in 36% of this population (baseline hemoglobin 11.5 g/dL) prevented recurrence of acute events in 71% of cases. Conclusions Our data suggest that hemoglobin SC disease should not be considered as a mild form of sickle cell anemia but as a separate disease with a special emphasis on viscosity-associated otological and ophthalmological disorders, and with a low prevalence of vasculopathy (strokes, pulmonary hypertension, ulcers and nephropathy). Phlebotomy was useful in reducing acute events and a wider use of this procedure should be further investigated.


Journal of The American Academy of Dermatology | 1995

Systemic mastocytosis associated with chronic myelomonocytic leukemia: Clinical features and response to interferon alfa therapy

A. Petit; Marc Pulik; Alain Gaulier; François Lionnet; Antoine Mahé; Michèle Sigal

Systemic mastocytosis is a rare disease that shows marked heterogeneity in clinical manifestations and prognosis. It may be associated with hematologic disorders. We describe a patient with systemic mastocytosis associated with chronic myelomonocytic leukemia accompanied by ascites, pleural effusion, and development of skin lesions along a surgical scar. The disease responded well to interferon alfa therapy. This is the second report of successful treatment of mastocytosis with interferon alfa and the first associated with a hematologic malignancy.


Thrombosis and Haemostasis | 2012

The acceleration of the propagation phase of thrombin generation in patients with steady-state sickle cell disease is associated with circulating erythrocyte-derived microparticles

Grigoris T. Gerotziafas; P. Van Dreden; Mourad Chaari; Vassiliki Galea; Amir Khaterchi; François Lionnet; K. Stankovic-Stojanovic; Olivier Blanc-Brude; B. Woodhams; M. Maier-Redelsperger; Robert Girot; Mohamed Hatmi; I. Elalamy

Sickle cell disease (SCD) is linked to hypercoagulability and is characterised by high concentrations of erythrocyte-derived microparticles (Ed-MPs). However, the impact of procoagulant cell-derived microparticles on the thrombin generation process remains unclear. We analysed the alterations of each phase of thrombin generation (TG) in relation to the concentration of erythrocyte- or platelet-derived microparticles (Ed-MPs and Pd-MPs) in a cohort of patients with steady-state SCD. We studied 92 steady-state SCD patients, 19 of which were under treatment with hydroxyurea, and 30 healthy age- and sex-matched individuals. TG was assessed by calibrated automated thrombogram. Ed-MP and Pd-MP expressing or not phosphatidylserine (PS) were determined by means of flow cytometry. Procoagulant phospholipid-dependent activity in the plasma was evaluated by the Procoag-PPL assay. Levels of thrombomodulin and haemoglobin in the plasma as well as red blood cell and reticulocyte counts were measured. SCD patients, independently of the administration of hydroxyurea, were marked by a significant acceleration in the propagation phase of TG which correlated with the Ed-MP/PS+ concentration. TG was significantly attenuated in hydroxyurea-treated patients. In conclusion, the acceleration of the propagation phase of TG, driven by Ed-MP/PS+, is a major functional alteration in blood coagulation in patients with steady-state SCD. Treatment with hydroxyurea, in addition to the regulation of haemolysis, lowers Ed-MPs and attenuates thrombin generation. The thrombogram could be a useful tool for the diagnosis of hypercoagulability and optimisation of the treatment in patients with SCD.


Blood Cells Molecules and Diseases | 2010

Strong association between a new marker of hemolysis and glomerulopathy in sickle cell anemia.

Micheline Maier-Redelsperger; Pierre Levy; François Lionnet; Katia Stankovic; Jean-Philippe Haymann; Guillaume Lefèvre; Virginie Avellino; Jean-Pierre Perol; Robert Girot; Jacques Elion

To perform a precise evaluation of the hemolytic status of patients with sickle cell anemia (SCA), advanced red blood cell parameters provided by the last generation analyzers were investigated in a series of SCA patients. The search for precise markers of hemolysis was performed to identify if patients so exposed develop organic complications related to a postulated hemolysis-linked endothelial dysfunction. Red blood cell survival was evaluated by the ratio between mature red blood cell (RBC) and reticulocyte (RET) hemoglobin (RBC-Hb/RET-Hb). In comparison with serum lactate dehydrogenase (LDH) and total bilirubin, the log (RBC-Hb/RET-Hb) was identified as the most discriminant hematological parameter to evaluate hemolysis. Furthermore, by combining this parameter with LDH, we defined a composite variable, which we called CVar, that is highly correlated with albuminuria and might constitute a powerful new marker of risk for this complication.


Clinical & Developmental Immunology | 2013

The association of CD81 polymorphisms with alloimmunization in sickle cell disease

Ryad Tamouza; Gama P. Le Bouder; Ramita Dewan; Naomi L.C. Luban; Jacqueline Lasserre; Jacqueline Maury; François Lionnet; Rajagopal Krishnamoorthy; Robert Girot; Stanislav Vukmanovic

The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization. Given that a subset of SCD patients develop multiple RBC allo-/autoantibodies, while others do not in a similar multiple transfusional setting, we investigated a possible genetic basis for alloimmunization. Biomarker(s) which predicts (predict) susceptibility to alloimmunization could identify patients at risk before the onset of a transfusion program and thus may have important implications for clinical management. In addition, such markers could shed light on the mechanism(s) underlying alloimmunization. We genotyped 27 single nucleotide polymorphisms (SNPs) in the CD81, CHRNA10, and ARHG genes in two groups of SCD patients. One group (35) of patients developed alloantibodies, and another (40) had no alloantibodies despite having received multiple transfusions. Two SNPs in the CD81 gene, that encodes molecule involved in the signal modulation of B lymphocytes, show a strong association with alloimmunization. If confirmed in prospective studies with larger cohorts, the two SNPs identified in this retrospective study could serve as predictive biomarkers for alloimmunization.


Haematologica | 2014

Impaired blood rheology plays a role in the chronic disorders associated with sickle cell-hemoglobin C disease

Nathalie Lemonne; Yann Lamarre; Marc Romana; Marie Dominique Hardy-Dessources; François Lionnet; Xavier Waltz; Vanessa Tarer; Danielle Mougenel; Benoît Tressières; Marie Laure Lalanne-Mistrih; Maryse Etienne-Julan; Philippe Connes

Lionnet et al. recently reported a high prevalence of retinopathy (RET) and otologic disorders (OTD) in patients with sickle cell-hemoglobin C disease (SC), while a significant number of patients had renal diseases (mainly glomerulopathy; GLO) and osteonecrosis (OST). The pathophysiological processes of these complications in SC are not well defined, although blood hyperviscosity has been suspected, but never tested to the best of our knowledge, as responsible for several chronic complications in SC disease1,2. The aim of this study was to analyze the associations between hematological and hemorheological parameters and chronic complications in adult SC patients.


Critical Care Medicine | 2014

Outcomes of Adult Patients With Sickle Cell Disease Admitted to the Icu: A Case Series*

Jérôme Cecchini; François Lionnet; Michel Djibré; Antoine Parrot; Katia Stankovic Stojanovic; Robert Girot; Muriel Fartoukh

Objective:Sickle cell disease is associated with a decreased life expectancy, half of the deaths occurring in the ICU. We aimed to describe the characteristics of sickle cell disease patients admitted to ICU and to identify early predictors of a complicated outcome, defined as the need for vital support or death. Design:Retrospective observational cohort study of sickle cell disease patients over a 6-year period. Setting:ICU of a French teaching hospital and sickle cell disease referral center. Patients:Hundred thirty-eight ICU admissions in 119 sickle cell disease patients. Interventions:None. Measurements and Main Results:ICU admission was mainly indicated for sickle cell disease–related events, especially acute chest syndrome. Mechanical ventilation, vasoactive drugs, and renal replacement therapy were administered to 25 (18%), 10 (7%), and 10 (7%) episodes, respectively. The complicated outcome group (n = 28; 20%) was characterized by a more aggressive acute disease within the 48 hours preceding ICU admission, with a higher respiratory rate, a more frequent acute kidney injury, and a more sustained drop of hemoglobin (all p < 0.01). All nine deaths (7%) were sickle cell disease related. None of the sickle cell disease baseline characteristics predicted accurately a complicated outcome. In multivariate analysis, hemoglobin less than or equal to 7.8 g/dL (odds ratio, 3.6; 95% CI, 1.1–11.9), respiratory rate more than or equal to 32 cycles/min (odds ratio, 5.6; 95% CI, 1.8–17.2), and acute kidney injury on ICU admission (odds ratio, 11.5; 95% CI, 2.5–52.6) were independently associated with a complicated outcome. Conclusions:Sickle cell disease patients are at high risk of complications when admitted to the ICU. A sustained drop of hemoglobin, acute respiratory distress, and kidney injury at admission are strong predictors of a complicated outcome.

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Nadjib Hammoudi

Institute of Chartered Accountants of Nigeria

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