Little is known about the effects of blood rheology on the occurrence of acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia and hemoglobin SC disease.
To ...address this issue, steady-state hemorheological profiles (blood viscosity, red blood cell deformability, aggregation properties) and hematologic parameters were assessed in 44 children with sickle cell anemia and 49 children with hemoglobin SC disease (8-16 years old) followed since birth. Clinical charts were retrospectively reviewed to determine prior acute chest syndrome or vaso-occlusive episodes, and rates of these complications were calculated.
Multivariate analysis revealed that: 1) a higher steady-state blood viscosity was associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, but not in children with hemoglobin SC disease; 2) a higher steady-state red blood cell disaggregation threshold was associated with previous history of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia.
Our results indicate for the first time that the red blood cell aggregation properties may play a role in the pathophysiology of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia. In addition, whereas greater blood viscosity is associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, no association was found in children with hemoglobin SC disease, underscoring differences in the etiology of vaso-occlusive crises between sickle cell anemia and hemoglobin SC disease.
Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a highly variable clinical course. ...Although high levels of microparticles (MPs) have been consistently reported in SCA and evidence of their harmful impact on the SCA complication occurrences have been provided, no data on MP pattern in HbSC patients has been reported so far. In this study, we determined and compared the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow cytometry. Most of circulating MPs were derived from platelets (PLTs) and red blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC patients exhibited lower blood concentration of total MPs compared to SCA patients, resulting mainly from a decrease of MP levels originated from RBCs and to a lesser extent from PLTs. We did not detect any association between blood MP concentrations and the occurrence of painful vaso-occlusive crises, acute chest syndrome and pulmonary hypertension in both patient groups. We also demonstrated for the first time, that whatever the considered genotype, RBC-derived MPs exhibited higher externalized phosphatidylserine level and were larger than PLT-derived MPs.
Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown.
Blood viscosity, red ...blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients.
Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age.
The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.
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.
To describe the characteristics of dengue in sickle cell children and try to identify risk factors of severity.
In this retrospective study, we describe the evolution according to genotype (SS or SC ...and controls) and severity.
From 2005 to 2013, 106 hospitalizations for dengue fever were recorded, 35 SS genotype, 35 SC and 36 without SCD or any other chronic disease. The clinical evolution was quite different. During hospitalization, SC patients were more likely to develop multiorgan failure (31.4% versus 25.7% for SS, and 0% for controls, p=0.001), or acute pulmonary complications than patients without SC sickle cell disease (14.3% versus 8.6% for SS, and 0% for controls, p=0.03). Level 3 analgesic treatment was more frequent in SC patients (22.9% versus 3% for SS, and 0% for controls, p<0.001). Patients with SC sickle cell disease had a higher proportion of severe forms of dengue (57.1% versus 37.1% for SS, and 0% for controls, p<0.001) than patients without SC sickle cell disease. Transfer in intensive care unit was required for most SC patients (22.9% versus 3% for SS, and 0% for controls, p=0.005).Fatal episodes were more frequent in SC patients than in patients without SC sickle cell disease (5 deaths versus 1 for SS and 0 for controls, p=0.02).
Thirty-three patients (47.1%) were diagnosed as having severe dengue (13 SS and 20 SC). On univariate analysis, age >10 years, acute pulmonary complications, multiorgan failure, severe anemia requiring transfusion, use of antibiotic treatment, need for treatment with morphine, and longer hospital stay were statistically more frequent in severe dengue-associated cases. Multiple logistic regression analysis showed that HbSC genotype and acute pulmonary complications, were significantly associated with severe dengue. In the multivariate model, the area of the ROC curve was 0.831. Children with SC genotype, typically thought to have less severe disease, actually had a higher rate of severe dengue and death than those with SS genotype.
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 exercise-induced 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.
BACKGROUND
HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and approved since 2007 in the European Union (EU) and ...2017 in the Unites States of America (USA) for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle cell disease (SCD). One risk raised for using a cytotoxic drug such as HU in children would be a potential negative impact on growth. Hence, a continuous follow-up of the growth of children treated with HU is recommended.
We hypothesized that as HU increased hemoglobin concentration and enhances quality of life it may have a positive impact on growth and even more significantly improve growth and nutritional status in SCD children, who are exposed by their disease to impaired growth due to higher metabolic rate, chronic anemia, and hypoxemia.
Here, we present preliminary results on growth development of sickle cell (SC) children enrolled in the ESCORT-HU study (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study whose objective is to evaluate the safety of HU in real life.
METHOD
Between January 2009 and June 2017, 1920 patients were enrolled from 63 centers in France, Germany, Greece and Italy. Of these 1920 patients, 849 (408 girls and 441 boys) were < 18 years of age.
Patients' follow-up in ESCORT-HU is strictly observational and follows usual recommendations and local clinical practices. Patients are seen by their physician approximately every 3 to 6 months. Weights, heights and Body Mass Index (BMI) were thus collected all along the study.
Patients previously treated with HU and HU-naïve before inclusion have been included in ESCORT-HU study which allowed comparison of these two groups of patients at inclusion in the study.
The French population reference measurement scale (growth curve AFPA -CRESS/INSERM) was used for comparison of growth in children enrolled in ESCORT-HU as approximately 83% of children were included in France.
RESULTS
547 children with reported height and/or weight were HU-naive at inclusion and 292 children were non-HU naive. Non-HU naïve patients had been treated for a median of 4.56 ± 3.29 years before inclusion in the ESCORT-HU cohort.
Median duration of observation in the ESCORT-HU study was 2.60 ± 1.67 years
Data on HU treatment and SC genotypes (90% SS) are displayed in table 1.
Both heights and weights between HU-naive and non-HU naive girls and boys at enrolment were significantly different (p<0.001) (table 2 and 3). Non-HU naive girls and boys were taller and heavier compared to HU-naive patients, suggesting a positive impact of HU on growth.
Mean heights and weights per age for girls were within the normal range all along the study with a mild decrease between 12 and 14 years old (Figure 1 and 2). For boys, weights and heights were within the normal range until the age of 11 and below the median normal range after 11 years (Figure 3 and 4).
Mean BMIs stayed within the normal range for all age groups (Figure 5 and 6) during the course of treatment with HU. 12% of HU naive patients had a low BMI at enrolment but this percentage decreased constantly all along HU treatment (7.2% at year 2 and 3% at year 5). On the contrary, 6% of the patient were overweight (BMI above the normal range) and this percentage increased all along HU treatment (9.9% at year 2 and 15.8% at year 5). Among overweight patients, only seven were reported to have obesity and the percentage remained stable.
CONCLUSION
In the ESCORT-HU study children who were non HU-naive at enrolment were heavier and taller than HU-naive patients, but these differences faded during the course of HU treatment which confirmed the absence of negative impact of HU on growth.
Heights and weights were within the normal range for girls whereas boys seemed to have a slower growth from 12 years of age. This difference may be due to pubertal delay in boys, but pubertal status was not collected in ESCORT-HU so this data could not be analysed. A minority of pediatric patients experienced overweight, suggesting to screen this possible complication.
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Therapeutic education is an integral part of the management of sickle cell patients. It includes the medical aspects but also the psychological, family and social repercussions of their chronic ...disease. It allows, at every stage of the patient's life, a care practice centred on the patient as a subject by offering him tools to become an effective actor of the management of complications, in the search for an acceptable quality of life.
Article Note: Sophie Antoine-Jonville and Philippe Connes equivalent position. Byline: Marc Romana, Karen Reminy, Berenike Moeckesch, Keyne Charlot, Marie-Dominique Hardy-Dessources, Lydia Doumdo, ...Benoit Tressieres, Maryse Etienne-Julan, Nathalie Lemonne, Christopher Denton, Thomas Coates, Marie Petras, Sophie Antoine-Jonville, Philippe Connes
Background
Sickle cell anaemia (SCA) is a severe hereditary haemoglobinopathy characterised by haemorheological abnormalities, which play a role in the occurrence of several acute and chronic ...clinical complications. While βS‐haplotypes and alpha‐thalassaemia modulate SCA clinical severity, their effects on blood rheology have been incompletely described. The aim of this study was to test the effects of these genetic modifiers on the haemorheological properties and clinical complication of children with SCA.
Procedure
Steady‐state haemorheological profile, biological parameters, βS‐haplotypes, alpha‐globin status, vaso‐occlusive crisis (VOC) and acute chest syndrome frequencies were analysed in 128 children (aged 5 to 18 years) with SCA.
Results
Patients with alpha‐thalassaemia showed increased red blood cell (RBC) deformability and aggregation compared to those without. Median VOC rate was higher in patients with homozygous alpha‐thalassaemia compared to those with a normal alpha genotype. Conversely, the haemorheological profile and clinical complications were not influenced by the βS‐haplotypes in our study.
Conclusion
Our results demonstrate that alpha‐thalassaemia is associated with higher risk for VOC events in children with SCA, which may be due in part to its effects on RBC deformability and aggregation.
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