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Connes P.,French Institute of Health and Medical Research | Connes P.,Institut Universitaire de France | Connes P.,University of Paris Pantheon Sorbonne | Connes P.,University of the French West Indies and Guiana | And 14 more authors.
British Journal of Haematology | Year: 2014

Although pulmonary hypertension, leg ulcers, priapism, stroke and glomerulopathy in sickle cell anaemia (SCA) result from the adverse effects of chronic haemolysis on vascular function (haemolytic phenotype), osteoneocrosis, acute chest syndrome and painful vaso-occlusive crises are caused by abnormal vascular cell adhesion and increased blood viscosity (viscosity-vaso-occlusion phenotype). However, this model with two sub-phenotypes does not take into account the haemorheological dimension. We tested the relationships between the biological parameters reflecting the haemolytic rate (haemolytic component) and red blood cell (RBC) rheological characteristics in 97 adults with SCA. No significant difference in the proportion of patients with low or high haemolytic component in the low and high blood viscosity groups was observed. The RBC elongation index (i.e. deformability) was negatively correlated with the haemolytic component. The RBC aggregates strength (i.e. RBC aggregates robustness) was negatively correlated with RBC elongation index. Sickle RBCs with high density had lower elongation index and higher aggregates strength. In conclusion, (i) the 'haemolytic' phenotype is characterized by decreased RBC deformability and increased RBC aggregates strength and (ii) the viscosity-vaso-occlusive phenotype is characterized by increased RBC deformability but not always by increased blood viscosity. α-thalassaemia modulates the haemorheological properties but other factors seem to be involved. © 2014 John Wiley & Sons Ltd.


Belaye L.,Center Hospitalier Et University Of Pointe tre | Lurel D.,rue Baudot | Ezelin F.,Center Hospitalier Et University Of Pointe tre | Cassin F.,Tour Massabielle | And 5 more authors.
Journal des Maladies Vasculaires | Year: 2016

Peripheral arterial disease of the lower limbs is a serious condition because of its local and general prognosis. Objectives: To identify the localization of peripheral arterial disease, associated risk factors, topography and features of the disease in Guadeloupe. Patients and methods: A descriptive non-interventional study was performed in Guadeloupe located in French West Indies from March to June 2014. Data for all patients, who underwent Doppler ultrasound of the lower limb in a vascular outpatient clinic and in the University Hospital in Guadeloupe for known or suspected peripheral arterial disease were included. Results: The study included 268 patients. Localizations were: infrapopliteal (n = 227 patients), popliteal (n = 148), femoral (n = 185) and aorto-iliac (n = 115). Smoking was associated with aorto-iliac (16 patients; P <. 0.05) and femoral (27 patients; P <. 0.05) localizations. Diabetes was associated with infrapopliteal localizations (133 patients; P <. 0.05), and high blood pressure was associated with infrapopliteal, popliteal and femoral localizations. Mean age was 73.1. ±. 10.8 years; half of patients (51 %) were women. Peripheral arterial disease was known for 52 % of the population; 147 patients were asymptomatic. Associated factors were high blood pressure (88 %), diabetes (63 %), dyslipidemia (45 %), and smoking (7 %). Ischemic heart disease was found in 14 % of patients, cerebrovascular disease in 18 % and all three localizations in 4 %. A history of amputation, bypass or endovascular treatment was found in 11 %, 20 % and 32 % of patients respectively. Conclusion: In our population, an infrapopliteal site was more often found than a proximal site. Distal localization was associated with diabetes, and proximal localization with smoking. Cardiovascular risk factors exhibited an atypical pattern with a large majority of patients (88 %) having high blood pressure, two-thirds diabetes, but with very few (7 %) smokers. Peripheral arterial disease was more often associated with a history of stroke than with ischemic heart disease. © 2016 Elsevier Masson SAS.


PubMed | rue Baudot, Center Hospitalier Et University Of Pointe tre, University of the French West Indies and Guiana and Tour Massabielle
Type: Journal Article | Journal: Journal des maladies vasculaires | Year: 2016

Peripheral arterial disease of the lower limbs is a serious condition because of its local and general prognosis.To identify the localization of peripheral arterial disease, associated risk factors, topography and features of the disease in Guadeloupe.A descriptive non-interventional study was performed in Guadeloupe located in French West Indies from March to June 2014. Data for all patients, who underwent Doppler ultrasound of the lower limb in a vascular outpatient clinic and in the University Hospital in Guadeloupe for known or suspected peripheral arterial disease were included.The study included 268patients. Localizations were: infrapopliteal (n=227patients), popliteal (n=148), femoral (n=185) and aorto-iliac (n=115). Smoking was associated with aorto-iliac (16patients; P<0.05) and femoral (27patients; P<0.05) localizations. Diabetes was associated with infrapopliteal localizations (133patients; P<0.05), and high blood pressure was associated with infrapopliteal, popliteal and femoral localizations. Mean age was 73.110.8years; half of patients (51%) were women. Peripheral arterial disease was known for 52% of the population; 147patients were asymptomatic. Associated factors were high blood pressure (88%), diabetes (63%), dyslipidemia (45%), and smoking (7%). Ischemic heart disease was found in 14% of patients, cerebrovascular disease in 18% and all three localizations in 4%. A history of amputation, bypass or endovascular treatment was found in 11%, 20% and 32% of patients respectively.In our population, an infrapopliteal site was more often found than a proximal site. Distal localization was associated with diabetes, and proximal localization with smoking. Cardiovascular risk factors exhibited an atypical pattern with a large majority of patients (88%) having high blood pressure, two-thirds diabetes, but with very few (7%) smokers. Peripheral arterial disease was more often associated with a history of stroke than with ischemic heart disease.


Waltz X.,University of the French West Indies and Guiana | Waltz X.,CEA DAM Ile-de-France | Waltz X.,University of Paris Pantheon Sorbonne | Romana M.,University of the French West Indies and Guiana | And 30 more authors.
PLoS ONE | Year: 2013

The six-minute walk test is a well-established submaximal exercise reflecting the functional status and the clinical severity of sickle cell patients. The aim of the present cross-sectional study was to investigate the biological determinants of the six-minute walk test performance in children with sickle cell anemia. Hematological and hemorheological parameters, pulmonary function and the six-minute walk test performance were determined in 42 children with sickle cell anemia at steady state. The performance during the six-minute walk test was normalized for age, sex and height and expressed as percentage of the predicted six-minute walk distance. We showed that a high level of anemia, a low fetal hemoglobin expression and low red blood cell deformability were independent predictors of a low six-minute walk test performance. This study describes for the first time the impact of blood rheology in the six-minute walk test performance in children with sickle cell anemia. © 2013 Waltz et al.


Waltz X.,French Institute of Health and Medical Research | Waltz X.,CEA DAM Ile-de-France | Waltz X.,University of the French West Indies and Guiana | Waltz X.,Service Of Pediatrie Du Center Hospitalier Et University Of Pointe tre | And 23 more authors.
Haematologica | Year: 2013

The aim of the study was to determine the factors associated with resting and exercise-induced hemoglobin oxygen desaturation. The well-established six-minute walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen saturation was measured before and immediately after the six-minute walk test. Blood samples were obtained on the same day to measure hematologic and hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the six-minute walk test compared to resting levels. No children with sickle hemoglobin C disease, but approximately 50% of children with sickle cell anemia showed mild or moderate oxygen desaturation at rest, which was independently associated with the percentage of reticulocytes. Exercise-induced hemoglobin oxygen desaturation was observed in 18% of children with sickle hemoglobin C disease and 34% of children with sickle cell anemia, and was independently associated with the six-minute walk test, acute chest syndrome rate and the strength of red blood cell aggregates in children with sickle cell anemia. No association was found in children with sickle hemoglobin C disease between exerciseinduced hemoglobin oxygen desaturation and the measured parameters. Hemoglobin oxygen desaturation at rest was common in children with sickle cell anemia but not in children with sickle hemoglobin C disease, and was mainly associated with greater hemolysis. Physiological strain during exercise and red blood cell aggregation properties may predict the occurrence of exercise-induced hemoglobin oxygen desaturation in children with sickle cell anemia. © 2013 Ferrata Storti Foundation.


Lamarre Y.,French Institute of Health and Medical Research | Hardy-Dessources M.-D.,French Institute of Health and Medical Research | Romana M.,French Institute of Health and Medical Research | Lalanne-Mistrih M.-L.,University of the French West Indies and Guiana | And 17 more authors.
Clinical Hemorheology and Microcirculation | Year: 2014

Vascular function has been found to be impaired in patients with sickle cell disease (SCD). The present study investigated the determinants of systemic vascular resistance in two main SCD syndromes in children: sickle cell anemia (SCA) and sickle cell-hemoglobin C disease (SCC). Nitric oxide metabolites (NOx), hematological, hemorheological, and hemodynamical parameters were investigated in 61 children with SCA and 49 children with SCC. While mean arterial pressure was not different between SCA and SCC children, systemic vascular resistance (SVR) was greater in SCC children. Although SVR and blood viscosity (ηb) were not correlated in SCC children, the increase of ηb (+18%) in SCC children compared to SCA children results in a greater mean SVR in this former group. SVR was positively correlated with ηb, hemoglobin (Hb) level and RBC deformability, and negatively with NOx level in SCA children. Multivariate linear regression model showed that both NOx and Hb levels were independently associated with SVR in SCA children. In SCC children, only NOx level was associated with SVR. In conclusion, vascular function of SCC children seems to better cope with higher ηb compared to SCA children. Since the occurrence of vaso-occlusive like complications are less frequent in SCC than in SCA children, this finding suggests a pathophysiological link between the vascular function alteration and these clinical manifestations. In addition, our results suggested that nitric oxide metabolism plays a key role in the regulation of SVR, both in SCA and SCC. © 2014 IOS Press and the authors. All rights reserved.


Waltz X.,French Institute of Health and Medical Research | Waltz X.,University of the French West Indies and Guiana | Pichon A.,University of Paris 13 | Mougenel D.,Center Hospitalier Et University Of Pointe tre | And 11 more authors.
American Journal of Hematology | Year: 2012

Sickle cell anemia (SS) is characterized by a reduced cerebral microvascular oxygen saturation (cerebral TOI), which is not associated with hemoglobin concentration. Cerebral TOI has never been studied in sickle cell-hemoglobin C disease (SC). We focused on the relationships between hemorheological alterations and cerebral TOI in sickle cell patients with no cerebral vasculopathy and on the usefulness of TOI variability to assess the cerebral vasomotion activity. The blood rheological profile, the level of cerebral TOI (spatial resolved spectroscopy) and the cerebral TOI variability, which reflects vasomotion activity, were compared between 20 healthy subjects (AA), 21 SC patients, and 21 SS patients. Cerebral TOI exhibited the following order: AA > SC > SS. The low cerebral TOI in SS patients was related to red blood cell aggregation and deformability properties. The cerebral TOI variability of SS and SC patients was increased above healthy values and vasomotion activity was negatively associated with the reduced cerebral TOI in SS patients. We demonstrated that (1) blood rheology could be involved in the reduced cerebral TOI in SS patients but not in SC patients; (2) vasomotion activity is increased in SS and SC patients to compensate for the reduced cerebral TOI. © 2012 Wiley Periodicals, Inc.


Connes P.,University of the French West Indies and Guiana | Connes P.,University of Paris Pantheon Sorbonne | Lamarre Y.,University of the French West Indies and Guiana | Lamarre Y.,University of Paris Pantheon Sorbonne | And 15 more authors.
PLoS ONE | Year: 2013

Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) - but with no leg ulcers at the time of the study - were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role. © 2013 Connes et al.


PubMed | University of the French West Indies and Guiana, Center Hospitalier Et University Of Pointe tre, French Institute of Health and Medical Research and University of Paris Pantheon Sorbonne
Type: Journal Article | Journal: Clinical hemorheology and microcirculation | Year: 2015

The hematocrit-to-viscosity ratio (HVR) has been widely used has an estimate of red blood cell (RBC) oxygen transport effectiveness into the microvasculature or as an oxygen delivery index. However, no study investigated the possibility of HVR to truly reflect RBC oxygen transport effectiveness or to be an oxygen delivery index. We measured blood viscosity at high shear rate (225 s(-1)), hematocrit, HVR, as well as the microvascular oxyhemoglobin saturation (TOI; tissue oxygen index) by spatial resolved near-infrared spectroscopy (NIRS) at cerebral and muscle levels in three population known to have various degrees of hemorheological abnormalities: healthy subjects (AA), patients with sickle cell SC disease (SC) characterized by moderate anemia and patients with sickle cell anemia (SS) marked by severe anemia. At both the cerebral and muscle level, HVR was positively correlated with TOI (r=0.28; p=0.03 and r=0.38; p=0.003, at the cerebral and muscle level, respectively). These findings suggest that HVR probably play a key role in blood flow and hemodynamic regulation in the microvasculature, hence modulating the amount of oxygen available for tissues. Nevertheless, the strengths of the associations are weak (R2<0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.

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