Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron overload is not uncommon in sickle cell disease (SCD) and requires regular chelation therapy in several instances. The present study evaluates the effect of deferiprone in 15 adult patients with SCD (ten beta(s)/beta(0)thalassemia and five beta(s)/beta(s)) and iron overload. Deferiprone was given at a dose of 75 mg/kg daily for 12 months. The evaluation considered pre- and post-treatment values of serum ferritin, urinary iron excretion, and T2 values of liver and heart obtained by magnetic resonance imaging (MRI). Eleven patients had a liver biopsy prior to starting therapy to evaluate iron concentration (LIC). Twelve patients completed the study with satisfactory compliance. In ten of them (83.3%) the serum ferritin levels decreased significantly at the end of the trial; in eight patients (66.6%) the reduction of serum ferritin was accompanied by a significant increase of their liver T2 values. All patients had a significant increase of urinary iron excretion in response to the drug. Ferritin levels and liver T2 values correlated with liver iron concentration; on the contrary, ferritin levels and liver T2 values failed to show any correlation with heart T2 values. Heart T2 values did not also show any correlation with left ventricular ejection fraction. Deferiprone was well tolerated and did not cause any significant adverse effects. These results suggest that deferiprone may effectively decrease the iron deposition in patients with SCD; moreover, T2 MRI proves to be a reliable and rapid, noninvasive method for assessing the liver iron load in patients with SCD.
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PMID:Deferiprone as an oral iron chelator in sickle cell disease. 1580 85

Transfusional iron overload may occur in the lungs. We hypothesized that quantitating siderophages in the bronchoalveolar fluid (BALF) of heavily transfused patients may prove to be a useful tool in determining lung iron overload in transfusion-dependent patients. The study included six patients (7-20 years) with thalassemia major (TM) who had received multiple blood transfusions, one with hereditary spherocytosis (four blood transfusions) and one with sickle cell disease (never transfused); they were compared to three children with idiopathic pulmonary hemosiderosis (IPH) (2.5-7.0 years) as positive controls. Fiberoptic bronchoscopy with bronchoalveolar lavage was performed in seven patients under general anesthesia for elective surgery and the rest were bronchoscoped electively under sedation. Spirometry was also performed in eight patients. There was no significant difference between children with TM and IPH in siderophages as percentage of total count (95% CI -31.0 to 1.5, P = 0.068). There were positive relationships between both mean serum ferritin values during the preceding year and the total number of units of transfused blood, and percent siderophage count among multiply transfused patients (P = 0.010, P = 0.052, respectively); similar findings were noted for the Golde score (P = 0.001, P = 0.031, respectively). None of the patients showed lung function impairment. In conclusion, in this small study, we found that the BALF of multiply transfused patients with benign hematological disorders contain similar numbers of siderophages to that of patients with IPH; this is strongly suggestive of secondary pulmonary hemosiderosis. The correlation between the patients' serum ferritin, and the BALF siderophages suggests that the later may serve as a marker of pulmonary iron overload in patients requiring blood transfusion and appear to be more sensitive than standard pulmonary function tests.
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PMID:Quantification of siderophages in bronchoalveolar fluid in transfusional and primary pulmonary hemosiderosis. 1687 95

Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin chain of the adult hemoglobin gene. This results in excess accumulation of unpaired alpha-chain gene products leading to reduced red blood cell life span and the development of severe anemia. Current treatment of this disease involves regular blood transfusion and adjunct chelation therapy to lower blood transfusion-induced iron overload. Fetal hemoglobin switching agents have been proposed to treat genetic blood disorders, such as sickle cell anemia and beta-thalassemia, in an effort to compensate for the dysfunctional form of the beta-globin chain in adult hemoglobin. The rationale behind this approach is to pair the excess normal alpha-globin chain with the alternative fetal gamma-chain to promote red blood cell survival and ameliorate the anemia. Reprogramming of differentiation in intact, mature, adult white blood cells in response to inclusion of monoclonal antibody CR3/43 has been described. This form of retrograde development has been termed "retrodifferentiation", with the ability to re-express a variety of stem cell markers in a heterogeneous population of white blood cells. This form of reprogramming, or reontogeny, to a more pluripotent stem cell state ought to recapitulate early hematopoiesis and facilitate expression of a fetal and/or adult program of hemoglobin synthesis or regeneration on infusion and subsequent redifferentiation. Herein, the outcome of infusion of autologous retrodifferentiated stem cells (RSC) into 21 patients with beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC subjected to hematopoietic-conducive conditions into patients with beta-thalassemia reduced mean blood transfusion requirement, increased mean fetal hemoglobin synthesis, and significantly lowered mean serum ferritin. This was always accompanied by an increase in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in such patients. No adverse side effects in response to the infusion of autologous RSC were noted. This novel clinical procedure may profoundly modify the devastating course of many genetic disorders in an autologous setting, thus paving the way to harnessing pluripotency from differentiated cells to regenerate transiently an otherwise genetically degenerate tissue such as thalassemic blood.
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PMID:Infusion of autologous retrodifferentiated stem cells into patients with beta-thalassemia. 1704 17

A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n = 199), and 64 non-Tx-SCD subjects to describe the frequency of iron-related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 +/- 11 years, mean +/- SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thal or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0-2.5) or non-Tx-SCD (RR = 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r= 0.20; P = 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 +/- 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality.
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PMID:Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload. 1709 96

Sickle cell disease (SCD) leads to many complications including osteoporosis and osteopenia. We studied the prevalence and predisposing factors of low bone mass density (BMD) in adults with SCD. In this retrospective study, dual X-ray absorptiometry bone scans were used to determine BMD in the lumbar spine, femoral neck and ultra distal radius of 103 patients (73 females, 30 males, aged 15-80 years). Chart reviews and a patient questionnaire were used to collect patient characteristics, disease course and severity, and low BMD risk factors. The 79.6% of patients (mean age 36.5 +/- 12.5 years) had an abnormal BMD, with a predilection for the lumbar spine (P = 0.001). Analysis by 3 (low BMD versus very low BMD versus normal) or by 2 groups (abnormal versus normal) showed that abnormal BMD was associated with lower body mass index (BMI) (P = 0.003), lower Hb level (P = 0.001) and higher ferritin (P = 0.003). Low BMD patients were more likely to be SS, SC or Sbeta(0)thal than Sbeta(+)thal (P = 0.022). Abnormal BMD was not related to age, sex, menarche, SCD complications, number of crises, iron overload, treatment with hydroxycarbamide or desferal, renal disease, smoking or alcohol. Patients treated with hydroxycarbamide for at least 6 months were more likely to have an abnormal BMD. In this SCD population, abnormal BMD seemed to be independent of sex, age and menopause, whereas BMI, ferritin level, Hb type and level appeared to play a major role.
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PMID:Bone mass density in adults with sickle cell disease. 1722 9

Serum ferritin (SF) and liver iron concentration (LIC), as measured by SQUID biosusceptometry, were assessed in a convenience sample of transfusion independent thalassemia patients (nTx-Thal, n=26), regularly transfused thalassemia (Tx-Thal, n=89), or sickle cell patients (SCD, n=45) to investigate the severity of iron overload and the relationship between SF and LIC in nTx-Thal compared to SCD and Tx-Thal. SF correlated with LIC (RS=0.53, P<0.001), but was found to be a poor predictor for LIC. SF was significantly lower (P<0.001) in nTx-Thal patients than in other groups, despite similar LIC values. The SF-to-LIC ratio was significantly lower in nTx-Thal compared to Tx-Thal and SCD patients (median of 0.32, 0.87, and 1.2, respectively: P<0.001). Due to underestimation of LIC by ferritin levels, chelation treatment may be delayed or misdirected in patients with thalassemia intermedia.
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PMID:Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients. 1755 89

Hypertransfusional (>8 transfusions/year) iron in liver biopsies collected immediately after transfusions in beta-thalassemia and sickle cell disease correlated with increased expression (RNA) for iron regulatory proteins 1 and 2 (3-, 9- to 11-fold) and hepcidin RNA: (5- to 8-fold) (each p <.01), while ferritin H and L RNA remained constant. A different H:L ferritin ratio in RNA (0.03) and protein (0.2-0.6) indicated disease-specific trends and suggests novel post-transcriptional effects. Increased iron regulatory proteins could stabilize the transferrin receptor mRNA and, thereby, iron uptake. Increased hepcidin, after correction of anemia by transfusion, likely reflects excess liver iron. Finally, the absence of a detectable change in ferritin mRNA indicates insufficient oxidative stress to significantly activate MARE/ARE promoters.
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PMID:Iron homeostasis during transfusional iron overload in beta-thalassemia and sickle cell disease: changes in iron regulatory protein, hepcidin, and ferritin expression. 1761 66

Deferasirox (Exjade) is an oral, once-daily iron chelator widely approved for the treatment of transfusional chronic iron overload. In the EU, deferasirox is indicated in patients with beta-thalassaemia major aged > or =6 years and, in the US, in all transfusional chronic iron overload patients aged > or =2 years. Deferasirox is highly selective for iron as Fe3+. In approximately 1-year clinical trials of patients with transfusional chronic iron overload associated with beta-thalassaemia, sickle cell disease, myelodysplastic syndrome or other rare chronic anaemias, deferasirox 20 or 30 mg/kg/day had a beneficial effect on liver iron concentrations (LIC) and serum ferritin levels; tolerability issues were clinically manageable with regular patient monitoring. Although longer-term efficacy and tolerability data are required, in particular examining the prevention of iron overload-related complications and the effect of deferasirox on renal function, deferasirox is an easily administered iron chelator and is a valuable option in the management of transfusional chronic iron overload.
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PMID:Deferasirox : a review of its use in the management of transfusional chronic iron overload. 1792 85

Sickle cell disease (SCD) is an autosomal, recessive hemoglobinopathy characterized by hemolytic anemia, intermittent occlusion of small vessels leading to acute and chronic tissue ischemia, and organ dysfunction. Red blood cell transfusions are a therapeutic mainstay in SCD and repeated transfusions can result in iron overload. Endocrine dysfunction is the most common and earliest organ toxicity seen in subjects with chronic iron-induced cellular oxidative damage and can be seen in those without clinical evidence of iron overload. The predicted risks of iron overload and endocrine organ failure increase with both the duration of disease requiring transfusion therapy and the number of transfusions. Assessing the state of iron-overload in patients with SCD constitutes a diagnostic challenge because of the unreliability of serum ferritin levels and the risks associated with liver biopsy. In turn, MRI is the preferred noninvasive screening tool for iron overload. This article describes the endocrine and metabolic disorders reported in patients with SCD, discusses their management, and identifies gaps in current knowledge and opportunities for future research.
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PMID:Therapy insight: metabolic and endocrine disorders in sickle cell disease. 1821 12

Iron overload occurs in patients who require regular blood transfusions to correct genetic and acquired anaemias, such as beta-thalassaemia major, sickle cell disease, and myelodysplastic syndromes. Although iron overload causes damage in many organs, accumulation of cardiac iron is a leading cause of death in transfused patients with beta-thalassaemia major. The symptoms of cardiac iron overload will occur long after the first cardiac iron accumulation, at a point when treatment is more complex than primary prevention would have been. Direct measurement of cardiac iron using T2* magnetic resonance imaging, rather than indirect methods such as measuring serum ferritin levels or liver iron concentration have contributed to earlier recognition of myocardial iron loading and prevention of cardiac toxicity. Cardiac siderosis occurs in all transfusional anaemias, but the relative risk depends upon the underlying disease state, transfusional load, and chelation history. All three available iron chelators can be used to remove cardiac iron, but each has unique physical properties that influence their cardiac efficacy. More prospective trials are needed to assess the effects of single-agent or combination iron chelation therapy on the levels of cardiac iron and cardiac function. Ultimately, iron chelation therapies should be tailored to meet individual patient needs and lifestyle demands.
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PMID:Cardiac iron across different transfusion-dependent diseases. 1905 52


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