Éditeur(s) : HAL CCSD
Résumé : Red blood cell hemodynamics influence blood rheology and thus circulatory function. Different authors showed that red blood cells are heterogeneous in blood flow. This heterogeneity could be explained by physical characteristics such as morphology, aggregability and deformability, but also by cellular and molecular environment. All these notions are found in sickle cell disease where sickle red blood cells become more rigid, leading to vascular occlusions, increased with an inflammatory context. In a preceding study, our results showed that velocity heterogeneity allow RBC classification, leading to different RBC sub-groups, using a dynamical approach and flow studies. In order to have a better understanding of the physiological meaning of such an heterogeneity, dynamical velocity experiences have been conducted in the case of normal and sickle red blood cells with different endothelial activations by proinflammatory cytokines, under a constant venular flow. Thus, normal and sickle red blood cells are classified into different sub-groups, showing their heterogeneity. Moreover, sub-population velocities and distribution evolve differently according to vascular state or treatment. These results show that red blood cell velocities and rheology depend on vascular environment and red blood cell morphology. However, the physiological meaning of this behavior should be explained by cellular and molecular effects of such activation.
https://hal.archives-ouvertes.fr/hal-00201461

hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461
https://hal.archives-ouvertes.fr/hal-00201461/document
https://hal.archives-ouvertes.fr/hal-00201461/file/RBCV_Marianne_v1.pdf

Résumé : Nous avons étudié les marqueurs hémorhéologiques, hématologiques et biochimiques chez des sujets drépanocytaires homozygotes SS (HbS/HbS) et hétérozygotes composites SC (HbS/HbC) dans deux cohortes, pédiatriques et adultes, de patients drépanocytaires, et ce, à travers 7 complications récurrentes de la drépanocytose : 2 appartenant au profil hémolytique (l’ulcère de jambes et la glomérulopathie) et 5 appartenant au phénotype visqueux/vaso-occlusif (l’hypertension artérielle, le syndrome thoracique aigu (STA), la crise vaso-occlusive (CVO), la rétinopathie et l’ostéonécrose). Nous avons montré que : 1) une viscosité sanguine et une déformabilité érythrocytaire élevées sont des facteurs de risques de CVO chez les enfants homozygotes ; 2) Une viscosité sanguine élevée est associée à une hypertension artérielle systémique relative chez des adultes SS ; 3) les enfants SC présente une fonction vasculaire mieux préservée que les enfants SS pour faire face à une augmentation de la viscosité sanguine ; 4) les patients adultes SS avec une ostéonécrose présentent une déformabilité érythrocytaire plus élevée que les patients sans ostéonécrose ; 5) une viscosité sanguine élevée est associée à la présence d’une rétinopathie chez les adultes SC mais pas chez les SS ; 6) les patients adultes SS présentant une glomérulopathie ont un taux d’hémolyse élevé, une déformabilité érythrocytaire réduite et des agrégats érythrocytaires très robustes ; 7) les patients adultes SS avec des ulcères de jambes récurrents ont un taux d’hémolyse accru et une déformabilité érythrocytaire réduite. De plus, nos travaux confirment que l’-thalassémie module les propriétés de déformabilité érythrocytaire, mais montrent pour la première fois qu’elle module aussi les propriétés d’agrégation érythrocytaire, et notamment la force des agrégats érythrocytaires. En conclusion, ces travaux permettent de préciser le rôle de la rhéologie sanguine dans un certain nombre de complications de la drépanocytose et d’enrichir le modèle préexistant divisant les complications de la drépanocytose selon 2 phénotypes : hémolytique versus visqueux/vaso-occlusif. Nous montrons pour la première fois que le phénotype hémolytique est caractérisé aussi par des anomalies de la rhéologie du globule rouge : rigidité accrue et agrégats érythrocytaire robustes.
Hemorheological, hemathological, and biochemical marquers of patients with sickle cell anemia (SS) and patients with sickle cell SC disease (SC) were studied in 2 cohorts: children and adults. We focused on 7 recurrent complications: 5 belonging to the viscosity/vaso-occlusion phenotype (systemic hypertension, acute chest syndrome (ACS), vaso-occlusive crisis (VOC), retinopathy and osteonecrosis) and 2 belonging to the hemolytic phenotype (leg ulcer and glomerulopathy). Our results show that 1) high viscosity is associated with increased risk for VOC in SS children; 2) blood viscosity is increased in SS adults with systemic relative hypertension; 3) SC children have preserved vascular function compared to SS children; 4) SS adults with osteonecrosis are characterized by higher red blood cell (RBC) deformability than SS adults without osteonecrosis; 5) high blood viscosity is associated with retinopathy in SC adults but not in SS adults; 6) SS adults affected by glomerulopathy have high hemolytic rate, low RBC deformability and increased RBC aggregates strenght; 7) SS adults with recurrent leg ulcers have high hemolytic rate and reduced RBC deformability. Moreover, our studies shows that alpha-thalassemia modulate RBC deformability and RBC aggregation properties. In conclusion, this work shows for the first time that the hemolytic phenotype is characterized by an abnormal RBC rheology which may play a role in several sickle cell complications.

http://www.theses.fr/2013AGUY0684/document

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Hemorheological abnormalities have been well characterized in sickle cell disease (SCD) and seem to modulate the clinical severity [1]. For instance, increased blood viscosity raises the risk for frequent vaso-occlusive crisis (VOC) and increased red blood cell (RBC) aggregates robustness (i.e., RBC disaggregation threshold) enhances the risks for acute chest syndrome (ACS) [2]. Moreover, patients with the most rigid RBCs are characterized by high hemolytic rate, which increases the risks to develop leg ulcers or glomerulopathy [3]. However, except few studies supporting an effect of alpha-thalassemia and oxidative stress [1] on RBC rheological properties of SCD patients, very few experiments focused on the genetic and cellular factors modulating blood rheology in this disease.
ISSN: 1079-9796

hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890/document
https://hal.archives-ouvertes.fr/hal-01263890/file/Ferdinand%20et%20al.%20eNOS%20and%20RBC%20rheology%20in%20SCD_BCMD.pdf
PUBMED : 26142331

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Patients with hemoglobin C disease (CC) usually do not develop severe complications in comparison with individuals with sickle cell anemia (SS) or with sickle cell hemoglobin C disease (SC). The present study compared the hematological, biochemical, hemorheological and clinical characteristics of CC patients to those of SS, SC and healthy individuals (AA). Blood viscosity was measured at 225 s(-1) with a cone plate viscometer. The hematocrit-to-blood viscosity ratio (HVR), i.e. an index of red blood cell (RBC) oxygen transport effectiveness, was calculated. RBC deformability was determined at 30 Pa by ektacytometry, and RBC aggregation properties by syllectometry. CC and SC had higher blood viscosity and lower HVR than AA. Nevertheless, HVR was higher in CC compared to SS and tended to be higher than in SC. The CC group exhibited very rigid hyperchromic RBC compared to the three other groups. RBC aggregation abnormalities were observed in CC: low RBC aggregation index and high RBC aggregates strength. Despite these hemorheological abnormalities, CC never had hospitalized painful vaso-occlusive crisis or acute chest syndrome. In contrast, all of them had splenomegaly. Of note, 2 out of 7 CC developed retinopathy or otologic disorders. Whether the blood hyperviscosity and decreased RBC deformability are responsible for these complications is unknown. The higher oxygen transport effectiveness (i.e., HVR) of CC compared to SS is probably at the origin of the very low risk of medical complication in this population.
ISSN: 1386-0291

hal-01668336
https://hal.univ-antilles.fr/hal-01668336
DOI : 10.3233/CH-141906

Éditeur(s) : HAL CCSD
Résumé : International audience
This study compared the hemorheological profile at rest and in response to a short supramaximal exercise test between sickle cell trait (SCT) carriers and a control group. Eight SCT carriers and eight control subjects performed a ramp exercise test on a cycle ergometer conducted to maximal oxygen uptake ðV_ O2maxÞ: One week later, they performed a supramaximal exercise test consisting of pedaling for 1 min at 110% V_ O2max: Blood viscosity (gb), plasma viscosity (gp), hematocrit (Hct) and red blood cell (RBC) rigidity were assessed at rest, at the end of exercise and at the 15th, 30th and 60th min of recovery. Exercise increased gb, gp and Hct above resting values in both groups and these parameters remained higher until the 15th or 30th min of recovery as compared to resting values. RBC rigidity was unchanged from baseline values in both groups during exercise and recovery. No difference was observed between the two groups for gp and Hct but gb and RBC rigidity were higher in the SCT carriers at every time point compared with the control group. The higher RBC rigidity and gb found in SCT carriers at rest and in response to a brief supramaximal exercise might constitute a risk factor for microcirculatory complications. Indeed, a short supramaximal exercise test may not be completely inoffensive for SCT carriers.
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY

hal-00706158
https://hal.univ-antilles.fr/hal-00706158
DOI : 10.1007/s00421-006-0155-3

Éditeur(s) : HAL CCSD ACSM
Résumé : International audience
A 26-yr-old man with sickle cell trait (SCT) suddenly lost visual acuity in the left eye after a cycling race in hot tropical environment. The cause was massive central retinal vein occlusion (CRVO) with hemorrhaging that rapidly worsened to neovascular glaucoma. Although medically treated, the eye is now marked by total retinal detachment. Cardiovascular function assessment shows no electrocardiographic abnormalities, no anomaly in the supra-aortic tree, and no evidence of structural heart disease. Although normal coagulation markers values (i.e., activated partial thromboplastin time, prothrombin time, fibrinogen concentration, antithrombin III, factor V, proteins C and S) were observed 2.5 months after the clinical event, a transesophageal echocardiogram performed few hours after the incident revealed the presence of four thrombi in the left atrium suggesting a postexercise hypercoagulable state at that time. Hemorheological measurements at distance of the events demonstrated high red blood cell rigidity at baseline. Therefore, marked blood rheological impairment and activation of the coagulation pathway in response to the heavy and prolonged cycling race could have promoted CRVO in this cyclist carrying SCT. These data suggest that SCT could be considered as a risk factor for significant ocular complications when severe exercise is performed and support the idea that SCT is a contributing factor in blood rheology and vascular dysfunctions.
Medicine & Science in Sports & exercise

Droits : info:eu-repo/semantics/OpenAccess
hal-00698572
https://hal.univ-antilles.fr/hal-00698572
https://hal.univ-antilles.fr/hal-00698572/document
https://hal.univ-antilles.fr/hal-00698572/file/Hedreville_et_al_revised_MSSE-D-08-00064R2.pdf
DOI : 10.1249/MSS.0b013e31818313d0

Éditeur(s) : HAL CCSD
Résumé : International audience
In this paper we present a microfluidic architecture dedicated to the study of Red Blood Cells (RBCs) deformability in microchannel smaller than the cell shape (biconcave disc of 7-8 μm in diameter) and cell capability to pass through slits separated by a gap value down to 2 μm, acting as a filter. This device is use in the context of RBCs disorders affecting their deformability, which is analysed versus number of cells trapped in the filter. This device can be seen as mimicking the human spleen. Microfabrication of the chip is based on polydimethylsiloxane (PDMS) associated to a two level thick photoresist mould (SU8). One level is used for microfluidic access with a 25 μm thickness towards the studied zone. The second level concerns the mimicking zones where RBCs flow through 5 μm down to 2 μm-wide slits acting like a mechanical filter. This level has a thickness of 5 μm. Devices have been tested on RBCs having specific disorder on their mechanical elasticity in order to validate the design principle. Two cases are presented in this paper: a.) Sickle RBCs inducing cell rigidity at two levels b.) Parasitized RBCs by Plasmodium falciparum. On both cases, we clearly show that deformability of RBCs influences the capability to pass through small slits (down to 2um) and thus is in relation with the pathology stage. This spleen-like microfluidic chip mimicking the RBCs filtering function is a promising tool for the exploration of RBC disorders combined with mechanical alterations.
4th European Conference on Microfluidics
Limerick, Ireland

hal-01113061
https://hal.archives-ouvertes.fr/hal-01113061