Optimal management of β thalassaemia intermedia

Taher, Ali T.; Musallam, Khaled M.; Cappellini, Maria Domenica; Weatherall, D. J.

doi:10.1111/j.1365-2141.2010.08486.x

Cited by 208 publications

(189 citation statements)

References 104 publications

(111 reference statements)

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…The most widely practiced indications for splenectomy in thalassemia are-mechanical discomfort due to huge splenomegaly, increased transfusion demand, poor growth/ development and hypersplenism [14]. In our study, the leading cause (51.39 %) for splenectomy was mechanical discomfort due to huge splenomegaly followed by increased transfusion requirement in 20.83 % patients.…”

Section: Discussionmentioning

confidence: 60%

Does Profile of Hemoglobin Eβ-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India

Mandal

Ghosh²,

Bhattacharyya³

2015

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

Hemoglobin Eb-thalassemia is by far the commonest form of thalassemia intermedia. Its phenotype ranges from mild anemia to severe transfusion-dependency necessitating splenectomy in many patients. The present study aimed to systematically analyze both clinical as well as laboratory parameters in profile of Eb-thalassemia patients after splenectomy in terms of transfusion requirement, infections and other complications. Retrospective study conducted over a period of 3 years included 72 cases of splenectomized Eb-thalassaemia patients, considering decrease in transfusion requirements, new complications, antibiotic, anti-malarial prophylaxis and iron chelation therapy. Out of 1380 registered Eb-thalassemia patients, 618 (44.78 %) were regularly transfused and 72(5.22 %) underwent splenectomy. Mean age of diagnosis was 10.3 years. Nineteen patients (26.4 %) underwent splenectomy between 5 and 10 years, 38 cases (52.7 %) between 10 and 20 years. The leading cause (51.39 %) for splenectomy was mechanical discomfort. Mean steady state hemoglobin raised from pre-splenectomy level of 5.43-6.8 gm/dl after splenectomy. Mean transfusion requirement reduced from 18.1 to 7.8 units/year. Mean serum ferritin level increased from 907.58 to 1,091.6 ng/ml. Post-splenectomy; 21 (29.17 %) patients developed facial deformities, 17 (23.6 %) delayed pubertal growth, 11 (15.28 %) venous thromboembolism, five (6.94 %) pulmonary hypertension and four (5.5 %) had extramedullary hematopoiesis. Five (6.96 %) patients had documented bacterial infections and two (2.78 %) suffered from malaria. Forty eight patients (66.67 %) started with iron chelation therapy; but majority (52.7 %) stopped. Major advantage of splenectomy is reduced transfusion requirement, though it cannot prevent skeletal abnormalities and delayed pubertal growth. In resource constraint countries like India, routine anti-malarial and antibacterial prophylaxis is not desirable; iron chelation therapy should be encouraged and ensured.

show abstract

Section: Discussionmentioning

confidence: 60%

Does Profile of Hemoglobin Eβ-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India

Mandal

Ghosh²,

Bhattacharyya³

2015

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

show abstract

“…1 In b-thalassemia intermedia, patients do not require regular blood transfusions. 1 Even without the added iron load of transfusions, pathological suppression of the iron-regulatory hormone hepcidin [2][3][4][5] in patients with b-thalassemia syndromes results in excessive iron absorption. Subsequent iron accumulation in the liver, endocrine glands, and other organs leads to oxidative damage and severe clinical complications predominantly involving hepatic, endocrine, and vascular systems, but sparing the heart, at least compared with transfused patients.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent iron accumulation in the liver, endocrine glands, and other organs leads to oxidative damage and severe clinical complications predominantly involving hepatic, endocrine, and vascular systems, but sparing the heart, at least compared with transfused patients. 1 Hepcidin acts by binding to ferroportin, 6 the sole known cellular iron exporter, leading to ubiquitination, internalization, and degradation of ferroportin in lysosomes. 7 Decreased hepcidin production leads to the stabilization of ferroportin at the cellular membrane and promotes the absorption of dietary iron in the duodenum.…”

Section: Introductionmentioning

confidence: 99%

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia

Kautz¹,

Jung²,

Du³

et al. 2015

Blood

265

262

View full text Add to dashboard Cite

Inherited anemias with ineffective erythropoiesis, such as β-thalassemia, manifest inappropriately low hepcidin production and consequent excessive absorption of dietary iron, leading to iron overload. Erythroferrone (ERFE) is an erythroid regulator of hepcidin synthesis and iron homeostasis. Erfe expression was highly increased in the marrow and spleen of HbbTh3/+ mice (Th3/+), a mouse model of thalassemia intermedia. Ablation of Erfe in Th3/+ mice restored normal levels of circulating hepcidin at 6 weeks of age, suggesting ERFE could be a factor suppressing hepcidin production in β-thalassemia. We examined the expression of Erfe and the consequences of its ablation in thalassemic mice from 3 to 12 weeks of age. The loss of ERFE in thalassemic mice led to full restoration of hepcidin mRNA expression at 3 and 6 weeks of age, and significant reduction in liver and spleen iron content at 6 and 12 weeks of age. Ablation of Erfe slightly ameliorated ineffective erythropoiesis, as indicated by reduced spleen index, red cell distribution width, and mean corpuscular volume, but did not improve the anemia. Thus, ERFE mediates hepcidin suppression and contributes to iron overload in a mouse model of β-thalassemia.

show abstract

“…1 This leads to an accumulation of α-globin and damage to the red blood cell (RBC) membrane which causes anemia and necessitates intermittent blood transfusion. TI may result from defective production of b-globin chains due to b-globin gene defects, or from the increased production of α-globin chains, resulting from a triplicate or quadruplicate α-genotype associated with b-thalassemia heterozygosity, the latter situation leading to a milder form of TI.…”

Section: Introductionmentioning

confidence: 99%

Thalassemic erythrocytes release microparticles loaded with hemichromes by redox activation of p72Syk kinase

Ferru

Pantaleo

Carta³

et al. 2013

Haematologica

View full text Add to dashboard Cite

© F e r r a t a S t o r t i F o u n d a t i o ndifferent genetic and clinical status provided new insights into the pathogenic role of circulating MP and possible interventions to control their amount in thalassemia. MethodsUnless otherwise stated, all materials were obtained from Sigma-Aldrich, St. Louis, MO, USA. Additional information about the methods are provided in the Online Supplementary Data. Treatment of red blood cellsVenous blood was drawn from 12 healthy individuals, eight non-splenectomized TI patients and six splenectomized TI patients. All subjects provided written, informed consent before entering the study. The study was approved by the local Ethics Committee and conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.Clinical analyses were performed by routine laboratory tests at the Policlinico Hospital (Milan, Italy). Blood anti-coagulated with heparin was stored in citrate-phosphate-dextrose with adenine (CPDA-1) prior to its use. RBC were washed three times with phosphate-buffered saline (PBS: 137mM NaCl, 2.7mM KCl, 8.1mM K 2 HPO 4 , 1.5mM KH 2 PO 4 , pH 7.4) containing glucose 5 mM to obtain packed RBC.To stimulate HMC formation, RBC from healthy donors were suspended at a hematocrit of 30% and incubated with different concentrations (0, 0.25, 0.5, 1, 1.5, 2 mM) of phenylhydrazine at 37 °C for 4 h. To test the antioxidant effect in MP release we incubated 200 μM of 2-mercaptoethanol in the presence of 1 mM phenylhydrazine. When necessary, RBC were pretreated with Syk kinase inhibitors (10 μM Syk inhibitors II and 10 μM Syk inhibitors IV, Calbiochem, Darmstadt, Germany), for 1 h at 37 °C in the dark. Each reaction was terminated by three washes with PBS-glucose. For all protocols described, untreated controls were processed identically except that the stimulant/inducer was omitted from the incubation. Red blood cell membrane preparationStandard hypotonic membranes were prepared, as previously described, 20 and stored frozen at -80°C until use. Membrane protein content was quantified using the DC Protein assay (Biorad, Hercules, CA, USA). Analysis of microparticlesThe MP in plasma were analyzed by flow cytometry using a modification of a previously described method:22 25 μL of plasma diluted 1:1 with PBS-glucose 5mM were analyzed using anti-CD41 (BD, Franklin Lakes, NJ, USA) and anti-glycophorin-A (Dako, Denmark), both diluted 1:10. Assay of hemichromesHMC were quantified by measuring heme absorbance (Abs) using the following equation:HMC= -133xAbs577 -114xAbs630 + 233xAbs560, and expressed as nMoles/mL of solubilized membranes. 23 Microparticle isolationTo induce MP release in vitro, RBC from each volunteer and phenylhydrazine-treated RBC in PBS (30% hematocrit) were incubated as previously described. 24 Electrophoresis and immunoblottingMembrane and MP proteins were solubilized in Laemmli buffer 25 under reducing [2% (w/v) dithiothreitol] or non-reducing conditions at a volume ratio of 1:1. Sodium dodecylsulfate polyacrylamide gel electropho...

show abstract

Optimal management of β thalassaemia intermedia

Cited by 208 publications

References 104 publications

Does Profile of Hemoglobin Eβ-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India

Does Profile of Hemoglobin Eβ-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India

Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia

Thalassemic erythrocytes release microparticles loaded with hemichromes by redox activation of p72Syk kinase

Contact Info

Product

Resources

About