[Show abstract][Hide abstract] ABSTRACT: Frequency and titers of autoantibodies in patients with sickle-cell disease (SCD) have been reported as relatively high. In a prospective study of 88 patients, we examined this "hyper-autoreactivity" and its clinical consequences.
For 1 year, patients with SCD were screened for the presence in their serum of antinuclear, anti-double-stranded DNA, antiextractible nuclear antigens, anticardiolipin antibodies, and rheumatoid factors. A population of 85 sex-matched individuals of similar ethnic origin served as controls.
Whereas prevalence of autoantibodies did not differ between the 2 groups, the type and rate of antinuclear antibodies were different. Autoantibodies from the SCD patients showed various immunofluorescence patterns, whereas only speckled patterns at low titers were present in controls. No antibody specificity was found in either group. SCD patients and controls displayed similar rates of anticardiolipin antibodies, but the SCD patients tended to be more frequently positive for rheumatoid factors. Six-year followup of the SCD patients did not provide any clinical evidence for onset of an autoimmune disease, except for 1 patient who developed rheumatoid arthritis, with increasing antinuclear antibodies followed by emergence of specific markers 5 years later.
Patients with SCD displayed high titers of autoantibodies. This observation may be due only to immune activation and/or dysfunction in SCD, as neither pathogenic specificity of autoantibodies nor autoimmune clinical signs appeared in the majority of cases in our study.
Full-text · Article · Feb 2011 · The Journal of Rheumatology
[Show abstract][Hide abstract] ABSTRACT: beta-thalassemia is a rare disease in France, encountered mainly in patients originating from Italy and North Africa. In the setting of the recent French plan for rare diseases, a National Registry for thalassemia has been developed since 2005. Epidemiological and clinical data have been collected on living patients with beta-thalassemia major or intermedia, including those who underwent hematopoietic stem cell transplantation.
A standardized questionnaire was sent to clinicians throughout the national professional networks involved in the management of thalassemic patients and data were updated every 18 months. A cross-sectional study was performed in February 2009.
Data on 378 patients (267 with thalassemia major) with a median age of 20 were recorded. Hematopoietic stem cell transplantation was performed in 52 patients. Stature, rates of parenthood, splenectomy, and cholecystectomy were no different between non-transplanted thalassemia major and thalassemia intermedia patients, after adjustment for age. Among the 215 non-transplanted thalassemia major patients, the median serum ferritin level was 1240 ng/mL and the rates of iron-related complications were 10%, 6%, 10% and 48% for cardiac failure, diabetes, hypothyroidism, and hypogonadism, respectively. From 2005 to 2008, a dramatic switch in chelation treatment, from deferoxamine to deferasirox, was observed.
The rates of complications of iron overload in French thalassemia major patients appeared similar to those reported in other developed countries in which this condition is not endemic. There were no significant differences in height and parenthood rates between patients with the major and the intermedia forms of the disease, underlining the progress in clinical care. Future developments will focus on mortality and morbidity under oral chelation treatment.
[Show abstract][Hide abstract] ABSTRACT: Hepatic complications are a major cause of death in patients with congenital anaemia and chronic hepatitis C. Ribavirin is usually contraindicated in patients with haemolytic anaemia. This pilot study evaluated the efficacy and safety of antiviral treatment in patients with sickle cell disease (SCD) or beta-thalassaemia major (TM).
Eleven consecutive SCD and TM patients were included. Interferon monotherapy was administrated in the two first thalassaemic patients. Other patients received combination therapy with full dose of pegylated interferon 2b and increasing doses of ribavirin, starting with a low dose of ribavirin (400 mg/day).
Hepatitis C virus genotypes were 1 or 4 in nine cases. A sustained virological response achieved in five of 11 patients despite unfavourable factors to response (genotypes, nonresponders to an earlier treatment). Haemoglobin level at the end of treatment was higher than baseline levels in five of six SCD patients. No SCD patient needed a transfusion during and after treatment period, neither presented vasoocclusive crisis. The mean increase in transfusion requirements was 32.5% in the thalassaemic group.
A sustained virological response can be obtained in SCD and TM patients. No earlier study of excellent haematological tolerance among SCD patients under ribavirin has been reported to date. The results of this study suggest that full dose ribavirin could be used from the start of treatment in SCD patients.
No preview · Article · May 2009 · European journal of gastroenterology & hepatology
[Show abstract][Hide abstract] ABSTRACT: Iron overload occurs in two categories of hematological diseases. 1) Hematological diseases inducing a spontaneous intestinal iron hyperabsorption, which can be treated through phlebotomies; 2) hematological diseases treated with regular transfusions of red blood cells, which require iron-chelating therapy. The main organs affected by iron overload are the heart, the liver, some endocrine glands (hypophysis, gonads, thyroid, parathyroid, endocrine pancreas) and bones. The evaluation of iron storage may be done through direct methods: measurement of liver iron concentration by means of liver biopsies, imaging techniques (SQUID method, RMN techniques). Indirect methods are used in routine medical practise: measurement of serum iron levels, transferrine saturation, and, overall, serum ferritin levels. Over the last forty years, the iron chelating treatment mainly used deferoxamine (Desféral®) with a dosage of 20-50 mg/kg body weight/day. The efficiency of this treatment was demonstrated thanks to a decreased mortality rate and morbidity for patients submitted to regular blood transfusion of red blood cells. The toxicity of deferoxamine is low. However, the parenteral mode of administration is not well tolerated and 20 to 40% of patients become bad compliant in the long term. Deferiprone (Ferriprox®, Kelfer®) is a drug given per os at a dosage of 75 mg/kg body weight/day, three times a day. In patients treated with deferiprone iron overload may decrease, increase or stay equal. Deferiprone seems to have a better protective effect against iron overload in the heart than deferoxamine. The main complications of deferiprone are neutropenia and arthralgias. Over the last five years, many clinicians treated their patients with both deferoxamine and deferiprone. Deferasirox (Exjade®) is an iron-chelating agent which is active per os. Several phase III trials including more than 1 000 patients were reported in December 2005. These reports showed deferasirox as having a global efficiency in reducing iron liver concentration and serum ferritin in patients receiving 25-30 mg/kg body weight/day during one year. This efficiency was non-inferior to that of deferoxamine given at the dosage 50 mg/kg body weight/day. An improvement of cardiac and/or hepatic anomalies preexisting to the treatment was observed in the patients at the end of the trial. The compliance to the treatment by deferasirox revealed to be highly better than that to treatment by deferoxamine. In the next future, deferasirox will be largely used in children and in adults to treat post transfusional iron overload. The expected issue of these on going long-term studies is the demonstration of a non-inferior effect of deferasirox versus deferoxamine regarding morbidity and mortality in patients regularly transfused with red blood cells.
[Show abstract][Hide abstract] ABSTRACT: Sickle cell disease (SCD) affects the kidney by acute mechanisms as well as by insidious renal medullary/papillary necrosis, resulting in tubular defects, which increase the risk of dehydration and subsequent sickle crisis. Hypoxia has been reported to stimulate endothelin-1 (ET-1) synthesis by endothelial cells and also in the renal tubule.
This case-control study measured ET-1 in urine as a marker of its renal synthesis in asymptomatic SCD patients. Baseline plasma and urinary ET-1 levels were measured and followed during a water deprivation study and a subsequent administration of desmopressin.
Urine and plasma levels of ET-1 were elevated in patients with SCD, compared with carefully matched African-French and African controls, and urine ET-1 excretion was associated with a marked urine-concentrating defect. Moreover, urinary ET-1 output was correlated with microalbuminuria in SCD patients.
ET-1 is known to antagonize the tubular effects of vasopressin and to promote renal scarring; increased renal production of ET-1 could produce nephrogenic diabetes insipidus and dehydration in SCD patients through a combination of fibrosis and functional resistance to vasopressin. This study provides a rationale for trials with endothelin receptor antagonists in sickle cell disease nephropathy.
Full-text · Article · Dec 2005 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Compliance with parenteral administration of deferoxamine is often poor in thalassemic patients with iron overload. We tested the efficacy and tolerance of the drug at high dosage 2 d per week for 24 months in two adult thalassemic patients with permanently high serum ferritin using a portable pump and an implanted chamber.
Deferoxamine was administered using a pressure-operated portable pump through an implanted chamber. The patients were infused over 48 h every week with 198 mg/kg/d (patient 1) and 170 mg/kg/d (patient 2). Serum ferritin levels were measured at regular intervals.
Serum ferritin decreased progressively from 2967 to 457 microg/L in patient 1 and from 6476 to 1951 microg/L in patient 2. Compliance and tolerance to treatment were excellent in the two patients.
Intravenous administration of high-dose deferoxamine over 48 h per week using a portable pump and implanted chamber improved compliance in two thalassemic adult patients, resulting in a significant decrease in iron overload. We suggest that high-dose chelation therapy should be assessed in selected groups of iron-overload thalassemic patients receiving regular blood transfusions.
No preview · Article · Nov 2001 · European Journal Of Haematology
[Show abstract][Hide abstract] ABSTRACT: Sickle cell disease patients suffering from frequent painful crises were submitted to phlebotomies in order to reduce hospitalization days due to pain, through hemoglobin (Hb) level reduction and iron deficiency in patients with an hemoglobin level equal to or above 9.5 g/dL.
Seven sickle cell disease patients (four SC, three SS), aged four to 24 years, were submitted to sequential phlebotomies during periods from 18 months to four years.
The number of hospitalization days for crises was considered. The volumes and frequencies of phlebotomies were adjusted according to the patients ages, the hemoglobin concentrations and the serum ferritin levels.
One hundred and forty-four hospitalization days were recorded in the seven patients in the year preceding the treatment. During the study period, the annual numbers of hospitalization days were respectively 20, five, six and one. Mean hemoglobin concentration was 10.7 g/dL before phlebotomies and 8.8 to 9.2 g/dL during the four years of treatment. Mean corpuscular volume, mean corpuscular hemoglobin concentration and serum ferritin were also reduced. The volume of phlebotomies was 116 to 39 mL/kg/year according to the patients.
The striking decrease of the number of hospitalization days for all the patients suggests a closed relationship between therapy and clinical improvement. The mechanism of this effect is probably multifactorial: a) the concentration of Hb level is known to influence the blood viscosity and its decrease always improved rheology in sickle cell disease patients; b) the mean corpuscular hemoglobin concentration is a critical factor concerning the HbS molecule polymerization in sickle cell disease, and its slight reduction may have an important biological effect. We observed these two biological modifications in our patients and suggest that they mediate the clinical effects. The iron deficiency induced by phlebotomies has no evident deleterious consequence either on height and weight in the children or on intellectual performance in any patients.
No preview · Article · Apr 2000 · Archives de Pédiatrie