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Achille Iolascon - One of the best experts on this subject based on the ideXlab platform.

  • Inherited Microcytic Anemias.
    Hematology. American Society of Hematology. Education Program, 2020
    Co-Authors: Maria Domenica Cappellini, Roberta Russo, Immacolata Andolfo, Achille Iolascon
    Abstract:

    Inherited Microcytic Anemias can be broadly classified into 3 subgroups: (1) defects in globin chains (hemoglobinopathies or thalassemias), (2) defects in heme synthesis, and (3) defects in iron availability or iron acquisition by the erythroid precursors. These conditions are characterized by a decreased availability of hemoglobin (Hb) components (globins, iron, and heme) that in turn causes a reduced Hb content in red cell precursors with subsequent delayed erythroid differentiation. Iron metabolism alterations remain central to the diagnosis of Microcytic Anemia, and, in general, the iron status has to be evaluated in cases of microcytosis. Besides the very common Microcytic Anemia due to acquired iron deficiency, a range of hereditary abnormalities that result in actual or functional iron deficiency are now being recognized. Atransferrinemia, DMT1 deficiency, ferroportin disease, and iron-refractory iron deficiency Anemia are hereditary disorders due to iron metabolism abnormalities, some of which are associated with iron overload. Because causes of microcytosis other than iron deficiency should be considered, it is important to evaluate several other red blood cell and iron parameters in patients with a reduced mean corpuscular volume (MCV), including mean corpuscular hemoglobin, red blood cell distribution width, reticulocyte hemoglobin content, serum iron and serum ferritin levels, total iron-binding capacity, transferrin saturation, hemoglobin electrophoresis, and sometimes reticulocyte count. From the epidemiological perspective, hemoglobinopathies/thalassemias are the most common forms of hereditary Microcytic Anemia, ranging from inconsequential changes in MCV to severe Anemia syndromes.

  • How I Diagnose Non-thalassemic Microcytic Anemias.
    Seminars in hematology, 2015
    Co-Authors: Mariasole Bruno, Luigia De Falco, Achille Iolascon
    Abstract:

    Microcytic Anemia is the most common form of Anemia, characterized by reduced hemoglobin (Hb) synthesis associated with decreased red blood cell volume (MCV). It is a very heterogeneous group of diseases that may be either acquired or inherited. Microcytic hypochromic Anemia can result from defects in globin (hemoglobinopathies or thalassemias) or heme synthesis or in iron availability, or acquisition by the erythroid precursors. Diagnosis of Microcytic anaemia appears to be important in children/adolescents, especially to set, where possible, a treatment plan on the basis of the etiology and pathogenesis. After excluding the acquired causes of Microcytic Anemia that represent the most frequent etiology, according to the differential diagnosis, the analysis of genetic causes, mostly hereditary, must be considered. This review will consider acquired and hereditary Microcytic Anemias due to heme synthesis or to iron metabolism defects and their diagnosis.

  • Molecular basis of inherited Microcytic Anemia due to defects in iron acquisition or heme synthesis.
    Haematologica, 2009
    Co-Authors: Achille Iolascon, Luigia De Falco, Carole Beaumont
    Abstract:

    Microcytic Anemia is the most commonly encountered Anemia in general medical practice. Nutritional iron deficiency and β thalassemia trait are the primary causes in pediatrics, whereas bleeding disorders and Anemia of chronic disease are common in adulthood. Microcytic hypochromic Anemia can result from a defect in globin genes, in heme synthesis, in iron availability or in iron acquisition by the erythroid precursors. These Microcytic Anemia can be sideroblastic or not, a trait which reflects the implications of different gene abnormalities. Iron is a trace element that may act as a redox component and therefore is integral to vital biological processes that require the transfer of electrons as in oxygen transport, oxidative phosphorylation, DNA biosynthesis and xenobiotic metabolism. However, it can also be pro-oxidant and to avoid its toxicity, iron metabolism is strictly controlled and failure of these control systems could induce iron overload or iron deficient Anemia. During the past few years, several new discoveries mostly arising from human patients or mouse models have highlighted the implication of iron metabolism components in hereditary Microcytic Anemia, from intestinal absorption to its final inclusion into heme. In this paper we will review the new information available on the iron acquisition pathway by developing erythrocytes and its regulation, and we will consider only inherited microcytosis due to heme synthesis or to iron metabolism defects. This information could be useful in the diagnosis and classification of these Microcytic Anemias.

  • A novel R416C mutation in human DMT1 (SLC11A2) displays pleiotropic effects on function and causes Microcytic Anemia and hepatic iron overload.
    Blood cells molecules & diseases, 2006
    Co-Authors: Steven Lam-yuk-tseung, Achille Iolascon, Clara Camaschella, Philippe Gros
    Abstract:

    A patient suffering from Microcytic Anemia and hepatic iron overload was found to be compound heterozygote for polymorphisms in the iron transporter DMT1 (Nramp2, SLC11A2), including a 3-bp deletion (DMT1(delCTT)) in intron 4 that partially impairs splicing and an amino acid substitution (DMT1(C1246T), R416C) at a conserved residue in transmembrane domain 9 of the protein. The functional properties and possible contribution to disease of the DMT1 R416C mutation were studied in independent mutants at that position (R416C, R416A, R416K, R416E) expressed in LLC-PK(1) kidney cells. Non-conservative substitutions at R416 (C, A, E) cause multiple functional deficiencies including defective protein processing, loss of transport activity, impaired cell surface targeting, and recycling through endosomes, concomitant with retention of the transporter in the endoplasmic reticulum. Conversely, a conservative isoelectric substitution (R416K) was less vulnerable, resulting in a functional transporter that was properly processed and targeted to the cell surface and to recycling endosomes. We propose that DMT1(C1246T) (R416C) represents a complete loss-of-function, and that a quantitative reduction in DMT1 expression is the cause of the Microcytic Anemia and iron overload in the patient.

  • Microcytic Anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2)
    Blood, 2005
    Co-Authors: Achille Iolascon, Maria D'apolito, Veronica Servedio, Flora Cimmino, Antonio Piga, Clara Camaschella
    Abstract:

    Divalent metal transporter 1 (DMT1) mediates apical iron uptake in duodenal enterocytes and iron transfer from the transferrin receptor endosomal cycle into the cytosol in erythroid cells. Both mk mice and Belgrade rats, which carry an identical DMT1 mutation, exhibit severe Microcytic Anemia at birth and defective intestinal iron use and erythroid iron use. We report the hematologic phenotype of a child, compound heterozygote for 2 DMT1 mutations, who was affected by severe Anemia since birth and showed hepatic iron overload. The novel mutations were a 3-bp deletion in intron 4 (c.310-3_5del CTT) resulting in a splicing abnormality and a C>T transition at nucleotide 1246(p. R416C). A striking reduction of DMT1 protein in peripheral blood mononuclear cells was demonstrated by Western blot analysis. The proband required blood transfusions until erythropoietin treatment allowed transfusion independence when hemoglobin levels between 75 and 95 g/L (7.5 and 9.5 g/dL) were achieved. Hematologic data of this patient at birth and in the first years of life strengthen the essential role of DMT1 in erythropoiesis. The early onset of iron overload indicates that, as in animal models, DMT1 is dispensable for liver iron uptake, whereas its deficiency in the gut is likely bypassed by the up-regulation of other pathways of iron use.

Yasufumi Masaki - One of the best experts on this subject based on the ideXlab platform.

  • castleman kojima disease tafro syndrome a novel systemic inflammatory disease characterized by a constellation of symptoms namely thrombocytopenia ascites anasarca Microcytic Anemia myelofibrosis renal dysfunction and organomegaly a status report and summary of fukushima 6 june 2012 and nagoya meetings 22 september 2012
    Journal of Clinical and Experimental Hematopathology, 2013
    Co-Authors: Hiroshi Kawabata, Kazue Takai, Masaru Kojima, Naoya Nakamura, Sadao Aoki, Shigeo Nakamura, Tomohiro Kinoshita, Yasufumi Masaki
    Abstract:

    Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, Microcytic Anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].

  • Castleman-Kojima Disease (TAFRO Syndrome) : A Novel Systemic Inflammatory Disease Characterized by a Constellation ofSymptoms, Namely, Thrombocytopenia, Ascites (Anasarca), Microcytic Anemia, Myelofibrosis, Renal Dysfunction, and Organomegaly : A Status Report
    2013
    Co-Authors: Hiroshi Kawabata, Kazue Takai, Masaru Kojima, Naoya Nakamura, Sadao Aoki, Shigeo Nakamura, Tomohiro Kinoshita, Yasufumi Masaki
    Abstract:

    Recently, a unique clinicopathologic variant of multicentric Castleman’s disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, Microcytic Anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. 〔J Clin Exp Hematop 53(1): 57-61, 2013〕

Carole Beaumont - One of the best experts on this subject based on the ideXlab platform.

  • Molecular basis of inherited Microcytic Anemia due to defects in iron acquisition or heme synthesis.
    Haematologica, 2009
    Co-Authors: Achille Iolascon, Luigia De Falco, Carole Beaumont
    Abstract:

    Microcytic Anemia is the most commonly encountered Anemia in general medical practice. Nutritional iron deficiency and β thalassemia trait are the primary causes in pediatrics, whereas bleeding disorders and Anemia of chronic disease are common in adulthood. Microcytic hypochromic Anemia can result from a defect in globin genes, in heme synthesis, in iron availability or in iron acquisition by the erythroid precursors. These Microcytic Anemia can be sideroblastic or not, a trait which reflects the implications of different gene abnormalities. Iron is a trace element that may act as a redox component and therefore is integral to vital biological processes that require the transfer of electrons as in oxygen transport, oxidative phosphorylation, DNA biosynthesis and xenobiotic metabolism. However, it can also be pro-oxidant and to avoid its toxicity, iron metabolism is strictly controlled and failure of these control systems could induce iron overload or iron deficient Anemia. During the past few years, several new discoveries mostly arising from human patients or mouse models have highlighted the implication of iron metabolism components in hereditary Microcytic Anemia, from intestinal absorption to its final inclusion into heme. In this paper we will review the new information available on the iron acquisition pathway by developing erythrocytes and its regulation, and we will consider only inherited microcytosis due to heme synthesis or to iron metabolism defects. This information could be useful in the diagnosis and classification of these Microcytic Anemias.

  • Two nonsense mutations in the TMPRSS6 gene in a patient with Microcytic Anemia and iron deficiency.
    Blood, 2008
    Co-Authors: Flavia Guillem, Caroline Kannengiesser, Carole Beaumont, Sarah Lawson, Mark Westerman, Bernard Grandchamp
    Abstract:

    Genetic causes of hypochromic Microcytic Anemia include thalassemias and some rare inherited diseases such as DMT1 deficiency. Here, we show that iron deficiency Anemia with poor intestinal absorption and defective iron utilization of IV iron is caused by inherited mutations in TMPRSS6, a liver-expressed gene that encodes a membrane-bound serine protease of previously unknown role that was recently reported to be a regulator of hepcidin expression.

  • Two new human DMT1 gene mutations in a patient with Microcytic Anemia, low ferritinemia, and liver iron overload.
    Blood, 2006
    Co-Authors: Carole Beaumont, Jean Delaunay, Gilles Hetet, Bernard Grandchamp, Mariane De Montalembert, Gil Tchernia
    Abstract:

    DMT1 mediates the pH-dependent uptake of Fe(2+) from the diet in duodenal enterocytes and in most other cells. It transfers iron from the endosomes to the cytosol following the uptake of the transferrin-transferrin receptor complex. DMT1 mutations are responsible for severe hypochromic Microcytic Anemia in rodents and in 2 human patients described recently. We report a compound heterozygote for 2 new DMT1 mutations, associated with Microcytic Anemia from birth and progressive liver iron overload. The first mutation is a GTG deletion in exon 5, leading to the V114 in-frame deletion in transmembrane domain 2, and the second is a G --> T substitution in exon 8 leading to the G212V replacement in transmembrane domain 5. Together with the 2 previously reported cases, this patient defines a new syndrome of congenital Microcytic hypochromic Anemia, poorly responsive to oral iron treatment, with liver iron overload associated paradoxically with normal to moderately elevated serum ferritin levels.

  • Two New Human DMT1 Mutations in a Compound Heterozygous Patient with Microcytic Anemia and Low Iron Stores.
    Blood, 2005
    Co-Authors: Carole Beaumont, Jean Delaunay, Gilles Hetet, Bernard Grandchamp, Mariane De Montalembert, Gil Tchernia
    Abstract:

    Abstract DMT1 is a divalent metal transporter with 12 transmembrane domains. It is expressed at the apical membrane of duodenal enterocytes, where it mediates pH-dependent uptake of Fe2+. In erythroid cells, it is found in the endosomal membrane where it transfers iron internalized through the transferrin-transferrin receptor pathway from the endosome to the cytosol. The same homozygous G>A substitution resulting in the G185A replacement is responsible for a severe hypochromic Microcytic Anemia in both the mk mouse and in the Belgrade rat. In humans, a homozygous G>C mutation has been described in a Czech patient, affecting the last nucleotide of exon 12. This mutation leads to the G399A replacement, without affecting the transport function of the protein. However, this mutation also induces a preferential in-frame skipping of exon 12, albeit not in all tissues. Accordingly, the patient has impaired iron acquisition in erythrocytes while duodenal iron absorption is increased leading to progressive iron overload. Here, we report a female patient born in 1996, with low birth weight and hypochromic Microcytic Anemia (Hb = 7.5 g/dl; MCV = 53 fL). She was transfused at day 0 and put on oral iron treatment. She was then lost to follow-up for five years. At the age of five, more extensive explorations showed a persistent Microcytic Anemia. The bone marrow displayed normal cellularity, 30% of nucleated cells were erythroid precursors with a moderate maturation defect, acidophilic forms being under-represented as compared to more immature forms. Soluble transferrin receptors were increased (8.3 mg/L; N = 0.83–1.76). Following oral iron therapy, serum ferritin levels remained low (15–25 μg/L; N = 14–197) despite an increase in transferrin saturation from 68 to 95 %. This high transferrin saturation resulted from the combination of reduced transferrin levels (1.64 g/L, N = 2.2–4.0) and increased serum iron levels (35 μmol/L; N = 11–24). On the other hand, hemoglobin raised from 7 to 9 g/dL only through increased number of RBC (5 to 5.7 T/L), since MCV and MCHC remained unchanged. We sequenced the entire transferrin receptor cDNA in this patient and found no mutation. We then sequenced the exons and the intron-exon boundaries of the DMT1 gene and found two heterozygous mutations. One mutation was a deletion of a GTG codon in exon 5, leading to the V114 in-frame deletion, in transmembrane domain 2. The other mutation is a G>T substitution in exon 8 leading to the G212V replacement in transmembrane domain 5. Both parents were asymptomatic, the father being heterozygous for the delV114 mutation and the mother heterozygous for the G212V mutation. This is the second patient described with a neonatal hypochromic Microcytic Anemia due to DMT1 mutations. Our data suggest that the two combined DMT1 mutations are responsible for the defect in iron utilization by erythroid cells, resulting in persistant microcytosis and impaired red cell maturation. The effect of the mutations on intestinal iron absorption is more difficult to evaluate since iron therapy allowed serum iron and transferrin saturation to increase but serum ferritin remained low and hemoglobin did not reach normal values.

Eloísa Urrechaga - One of the best experts on this subject based on the ideXlab platform.

  • Verification of 20 Mathematical Formulas for Discriminating Between Iron Deficiency Anemia and Thalassemia Trait in Microcytic Anemia
    Laboratory medicine, 2020
    Co-Authors: Johannes J M L Hoffmann, Eloísa Urrechaga
    Abstract:

    BACKGROUND Currently, more than 45 mathematical formulas based on simple red blood cell (RBC) parameters have been proposed for differentiating between iron deficiency and thalassemia in Microcytic Anemia, of which 20 are relatively new and have not been thoroughly independently verified. The study goal was to verify these 20 new formulas and to identify which RBC parameters have a decisive impact on the performance of those formulas. METHODS A database containing laboratory and diagnostic data from 2788 subject individuals with Microcytic Anemia was used for assessing performance by receiver operating characteristic (ROC) analysis. RESULTS The new Index26 had excellent performance, equivalent to the Green and King, Jayabose, and Janel formulas previously identified in the literature. The discriminant power of nearly all newer formulas was lower in our study than that claimed by the original authors. We discovered that a well-performing formula requires mean cell volume (MCV), RBC distribution width (RDW), and RBC measurements, whereas hemoglobin measurements appeared not to be essential. CONCLUSIONS Only the new Index26 performed at a level comparable to the very strongest established formulas. All other new formulas had lower performance than was claimed in the original publications, underscoring that independent verification of new formulas is indispensable.

  • critical appraisal of discriminant formulas for distinguishing thalassemia from iron deficiency in patients with Microcytic Anemia
    Clinical Chemistry and Laboratory Medicine, 2017
    Co-Authors: Eloísa Urrechaga, Johannes J M L Hoffmann
    Abstract:

    Background Many discriminant formulas have been reported for distinguishing thalassemia trait from iron deficiency in patients with Microcytic Anemia. Independent verification of several discriminant formulas is deficient or even lacking. Therefore, we have retrospectively investigated discriminant formulas in a large, well-characterized patient population. Methods The investigational population consisted of 2664 patients with Microcytic Anemia: 1259 had iron deficiency, 1196 'pure' thalassemia trait (877 β- and 319 α-thalassemia), 150 had thalassemia trait with concomitant iron deficiency or Anemia of chronic disease, and 36 had other diseases. We investigated 25 discriminant formulas that only use hematologic parameters available on all analyzers; formulas with more advanced parameters were disregarded. The diagnostic performance was investigated using ROC analysis. Results The three best performing formulas were the Jayabose (RDW index), Janel (11T), and Green and King formulas. The differences between them were not statistically significant (p>0.333), but each of them had significantly higher area under the ROC curve than any other formula. The Jayabose and Green and King formulas had the highest sensitivities: 0.917 both. The highest specificity, 0.925, was found for the Janel formula, which is a composite score of 11 other formulas. All investigated formulas performed significantly better in distinguishing β- than α-thalassemia from iron deficiency. Conclusions In our patient population, the Jayabose RDW index, the Green and King formula and the Janel 11T score are superior to all other formulas examined for distinguishing between thalassemia trait and iron deficiency Anemia. We confirmed that all formulas perform much better in β- than in α-thalassemia carriers and also that they incorrectly classify approximately 30% of thalassemia carriers with concomitant other Anemia as not having thalassemia. The diagnostic performance of even the best formulas is not high enough for making a final thalassemia diagnosis, but in countries with limited resources, they can be helpful in identifying those patients who need further examinations for genetic Anemia.

  • differential diagnosis of Microcytic Anemia the role of Microcytic and hypochromic erythrocytes
    International Journal of Laboratory Hematology, 2015
    Co-Authors: Eloísa Urrechaga, Silvia Izquierdo, J J M L Hoffmann, Jesús F. Escanero
    Abstract:

    SUMMARY Introduction: Various indices derived from red blood cell (RBC) parameters have been described for distinguishing thalassemia and iron deficiency. We studied the Microcytic to hypochromic RBC ratio as a discriminant index in Microcytic Anemia and compared it to traditional indices in a learning set and confirmed our findings in a validation set. Methods: The learning set comprised samples from 371 patients with Microcytic Anemia mean cell volume (MCV 6.4 was strongly indicative of thalassemia (area under the curve 0.948). Green-King and England-Fraser indices showed comparable area under the ROC curve. However, the Microcytic to hypochro- mic ratio had the highest sensitivity (0.964). In the validation set, 91.1% of Microcytic patients were correctly classified using the M/ H ratio. Conclusions: Overall, the Microcytic to hypochromic ratio as measured in CELL-DYN Sapphire performed equally well as the Green-King index in identifying thalassemia carriers, but with higher sensitivity, making it a quick and inexpensive screening tool.

  • Multivariable Discriminant Analysis for the Differential Diagnosis of Microcytic Anemia
    Anemia, 2013
    Co-Authors: Eloísa Urrechaga, Urko Aguirre, Silvia Izquierdo
    Abstract:

    Introduction. Iron deficiency Anemia and thalassemia are the most common causes of Microcytic Anemia. Powerful statistical computer programming enables sensitive discriminant analyses to aid in the diagnosis. We aimed at investigating the performance of the multiple discriminant analysis (MDA) to the differential diagnosis of Microcytic Anemia. Methods. The training group was composed of 200 β-thalassemia carriers, 65 α-thalassemia carriers, 170 iron deficiency Anemia (IDA), and 45 mixed cases of thalassemia and acute phase response or iron deficiency. A set of potential predictor parameters that could detect differences among groups were selected: Red Blood Cells (RBC), hemoglobin (Hb), mean cell volume (MCV), mean cell hemoglobin (MCH), and RBC distribution width (RDW). The functions obtained with MDA analysis were applied to a set of 628 consecutive patients with Microcytic Anemia. Results. For classifying patients into two groups (genetic Anemia and acquired Anemia), only one function was needed; 87.9% β-thalassemia carriers, and 83.3% α-thalassemia carriers, and 72.1% in the mixed group were correctly classified. Conclusion. Linear discriminant functions based on hemogram data can aid in differentiating between IDA and thalassemia, so samples can be efficiently selected for further analysis to confirm the presence of genetic Anemia.

  • The role of automated measurement of RBC subpopulations in differential diagnosis of Microcytic Anemia and β-thalassemia screening.
    American journal of clinical pathology, 2011
    Co-Authors: Eloísa Urrechaga, L. Borque, Jesús F. Escanero
    Abstract:

    Cell counter-based formulas have been used in the differential diagnosis of Microcytic Anemia. The measurement of RBC subpopulations is now available on the Sysmex XE 5000 analyzer (Sysmex, Kobe, Japan). We describe the new formulas: % Microcytic - % hypochromic; and % Microcytic - % hypochromic - red cell distribution width (RDW), derived from the percentages of Microcytic and hypochromic RBCs. The present study aimed to prospectively evaluate the reliability of these new formulas in the differential diagnosis of microcytosis and β-thalassemia screening compared with already published indices. The indices were calculated for a set of 250 iron-deficient patients and 270 β-thalassemia carriers. Independent samples t test and receiver-operating characteristics analysis were applied. The % Microcytic - % hypochromic - RDW, % Microcytic - % hypochromic, and Green and King indices provided higher areas under the curve. The % Microcytic - % hypochromic - RDW was the most reliable index evaluated, with 100% sensitivity and 92.6% specificity. This index can be used to efficiently screen patients with microcytosis for further hematologic studies to confirm β-thalassemia.

Hiroshi Kawabata - One of the best experts on this subject based on the ideXlab platform.

  • castleman kojima disease tafro syndrome a novel systemic inflammatory disease characterized by a constellation of symptoms namely thrombocytopenia ascites anasarca Microcytic Anemia myelofibrosis renal dysfunction and organomegaly a status report and summary of fukushima 6 june 2012 and nagoya meetings 22 september 2012
    Journal of Clinical and Experimental Hematopathology, 2013
    Co-Authors: Hiroshi Kawabata, Kazue Takai, Masaru Kojima, Naoya Nakamura, Sadao Aoki, Shigeo Nakamura, Tomohiro Kinoshita, Yasufumi Masaki
    Abstract:

    Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, Microcytic Anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].

  • Castleman-Kojima Disease (TAFRO Syndrome) : A Novel Systemic Inflammatory Disease Characterized by a Constellation ofSymptoms, Namely, Thrombocytopenia, Ascites (Anasarca), Microcytic Anemia, Myelofibrosis, Renal Dysfunction, and Organomegaly : A Status Report
    2013
    Co-Authors: Hiroshi Kawabata, Kazue Takai, Masaru Kojima, Naoya Nakamura, Sadao Aoki, Shigeo Nakamura, Tomohiro Kinoshita, Yasufumi Masaki
    Abstract:

    Recently, a unique clinicopathologic variant of multicentric Castleman’s disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, Microcytic Anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. 〔J Clin Exp Hematop 53(1): 57-61, 2013〕