T2* MRI in Regularly Transfused Children with Thalassemia Intermedia: Serum Ferritin Does Not Reflect Liver Iron Stores

Tony, Surekha; Daar, Shahina; Elshinawy, Mohamed; Al-Zadjaly, Shoaib; Al-Khabori, Murtadha; Wali, Yasser

doi:10.3109/08880018.2012.708891

Cited by 12 publications

(10 citation statements)

References 27 publications

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“…After being on chronic transfusion therapy for four months, his growth improved to the 25 th centile, and his liver and spleen are palpable just under the costophrenic angle. The modest elevation in ferritin level, which is discrepant with the T2* of his liver showing moderate iron overload, is similar to what has been reported in patients with thalassemia intermedia [18]. Also, iron loading in thalassemia intermedia can occur even in the absence of prolonged transfusion therapy and responds well to iron chelation therapy [19].…”

Section: Resultssupporting

confidence: 68%

Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: Review of all reported cases and development of a clinical diagnostic paradigm

Jaffray

Mitchell

Gnanapragasam

et al. 2013

Blood Cells, Molecules, and Diseases

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KLF1 is an erythroid specific transcription factor that is involved in erythroid lineage commitment, globin switching and terminal red blood cell maturation. Various mutations of KLF1 have been identified in humans, which has led to both benign and pathological phenotypes. The E325K mutation, within the second zinc finger of the KLF1 gene, has been shown to cause a new form of congenital dyserythropoietic anemia (CDA) now labeled as CDA type IV. We report the fourth documented case of this mutation, and propose a clinical diagnostic model to better identify this disease in other patients. Our patient is a Taiwanese child who presented to us at 8 years of age with severe hemolytic anemia, splenomegaly, elevated fetal hemoglobin (HbF), iron overload, and dyserythropoiesis in the bone marrow. KLF1 sequence analysis revealed a G-to-A transition in one allele of exon 3, which resulted in the substitution of a glutamate 325 by a lysine. Flow cytometry analysis revealed decreased protein expression of CD44 on the red blood cells, and decreased red blood cell deformability as measured using an ektacytometer. Blood typing revealed his red blood cells to be Co(a−b−), In(b−), LW(ab−) and Lu(b+), even though DNA testing predicted he would be Co(a+b−) and LW(a+b−ab+). This newly discovered CDA combines features of a hemoglobinopathy, RBC membrane defect and hereditary persistence of HbF (HPFH) which is not seen in previous types of CDA. Increased awareness of this phenotype may improve more prompt and accurate diagnosis of these patients.

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Section: Resultssupporting

confidence: 68%

Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: Review of all reported cases and development of a clinical diagnostic paradigm

Jaffray

Mitchell

Gnanapragasam

et al. 2013

Blood Cells, Molecules, and Diseases

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“…It has been observed that serum ferritin levels can underestimate iron load in patients with β‐TI, compared with patients with thalassaemia major. Therefore, relying on this measurement may expose patients with NTDT to high iron levels and delay necessary chelation therapy . Similar findings were reported in the THALASSA trial of deferasirox in patients with NTDT including HbE/β‐thalassaemia and α‐thalassaemia .…”

Section: Transfusion Considerationssupporting

confidence: 66%

When to consider transfusion therapy for patients with non‐transfusion‐dependent thalassaemia

2014

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Non-transfusion-dependent thalassaemia (NTDT) refers to all thalassaemia disease phenotypes that do not require regular blood transfusions for survival. Thalassaemia disorders were traditionally concentrated along the tropical belt stretching from sub-Saharan Africa through the Mediterranean region and the Middle East to South and South-East Asia, but global migration has led to increased incidence in North America and Northern Europe. Transfusionists may be familiar with β-thalassaemia major because of the lifelong transfusions needed by these patients. Although patients with NTDT do not require regular transfusions for survival, they may require transfusions in some instances such as pregnancy, infection or growth failure. The complications associated with NTDT can be severe if not properly managed, and many are directly related to chronic anaemia. Awareness of NTDT is important, and this review will outline the factors that should be taken into consideration when deciding whether to initiate and properly plan for transfusion therapy in these patients in terms of transfusion interval and duration of treatment.

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“…ref. [149][150][151][152][153][154][155][156][157][158], also widely used for brain imaging (e.g. ref.…”

Section: Serum Ferritin Can Be a Marker Of Iron Stores But Is Also Anmentioning

confidence: 99%

Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells

2014

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"Serum ferritin" presents a paradox, as the iron storage protein ferritin is not synthesised in serum yet is to be found there. Serum ferritin is also a well known inflammatory marker, but it is unclear whether serum ferritin reflects or causes inflammation, or whether it is involved in an inflammatory cycle. We argue here that serum ferritin arises from damaged cells, and is thus a marker of cellular damage. The protein in serum ferritin is considered benign, but it has lost (i.e. dumped) most of its normal complement of iron which when unliganded is highly toxic. The facts that serum ferritin levels can correlate with both disease and with body iron stores are thus expected on simple chemical kinetic grounds. Serum ferritin levels also correlate with other phenotypic readouts such as erythrocyte morphology. Overall, this systems approach serves to explain a number of apparent paradoxes of serum ferritin, including (i) why it correlates with biomarkers of cell damage, (ii) why it correlates with biomarkers of hydroxyl radical formation (and oxidative stress) and (iii) therefore why it correlates with the presence and/or severity of numerous diseases. This leads to suggestions for how one might exploit the corollaries of the recognition that serum ferritin levels mainly represent a consequence of cell stress and damage.

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T2* MRI in Regularly Transfused Children with Thalassemia Intermedia: Serum Ferritin Does Not Reflect Liver Iron Stores

Cited by 12 publications

References 27 publications

Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: Review of all reported cases and development of a clinical diagnostic paradigm

Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: Review of all reported cases and development of a clinical diagnostic paradigm

When to consider transfusion therapy for patients with non‐transfusion‐dependent thalassaemia

Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells

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