Critical appraisal of discriminant formulas for distinguishing thalassemia from iron deficiency in patients with microcytic anemia

2017 ◽  
Vol 55 (10) ◽  
Author(s):  
Eloísa Urrechaga ◽  
Johannes J.M.L. Hoffmann
Keyword(s):  
Iron Deficiency ◽  
Patient Population ◽  
Diagnostic Performance ◽  
Roc Analysis ◽  
Critical Appraisal ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Anemia Of Chronic Disease ◽  
Independent Verification ◽  
Thalassemia Trait

AbstractBackground: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.

Verification of 20 Mathematical Formulas for Discriminating Between Iron Deficiency Anemia and Thalassemia Trait in Microcytic Anemia

2020 ◽  
Vol 51 (6) ◽  
pp. 628-634 ◽  
Author(s):  
Johannes J M L Hoffmann ◽  
Eloísa Urrechaga
Keyword(s):  
Iron Deficiency ◽  
Operating Characteristic ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Mean Cell Volume ◽  
Distribution Width ◽  
Independent Verification ◽  
Mathematical Formulas ◽  
Thalassemia Trait ◽  
Discriminant Power

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.

scholarly journals Reticulocyte hemoglobin equivalent in differential diagnosis of iron deficiency, iron deficiency anemia and β thalassemia trait in children.

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Yeter Düzenli Kar ◽  
Konca Altınkaynak
Keyword(s):  
Differential Diagnosis ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Roc Analysis ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Healthy Children ◽  
Hypochromic Microcytic Anemia ◽  
Thalassemia Trait ◽  
Diagnostic Power

AbstractObjectivesThis study investigated the diagnostic power of reticulocyte hemoglobin equivalent (Ret-He) in the differential diagnosis of hypochromic microcytic anemia to differentiate iron deficiency anemia (IDA) and thalassemia trait (TT) based on the traditionally used erythrocyte index and formulas.MethodsTwenty-six children with iron deficiency (ID), 26 with IDA, 33 with β-TT, 41 healthy children were assessed. Complete blood count parameters, Ret-He, immature reticulocyte fraction (IRF), low-fluorescence ratio (LFR), Mentzer’s indexes (MI) were evaluated. The diagnostic power of Ret-He in distinguishing between IDA and β-TT was investigated using ROC analysis.ResultsRet-He levels were (median(Q1-Q3)) 20.6(19.7–21.5) pg in β-TT, 16.1(13.1–20) pg in IDA, 29.7(27.2–30.7) pg in ID, 30.5(29.8–31.7) pg in healthy controls. Based on ROC analysis, diagnostic power for distinguishing between IDA and β-TT was determined as RBC>MI>Ret-He>RDW>LFR>IRF. The highest sensitivity and specificity for differential diagnosis was obtained when the Ret-He cut-off value was 18.2pg. The AUC (95%CI) value was calculated as 0.765(0.637–0.866), and a statistically significant difference was found between groups (p<0.0006).ConclusionsIn patients with hypochromic microcytic anemia, Ret-He≤18.2pg combined with RBC≤5.3x106/L and MI>10.42 can be safely used to distinguish IDA from β-TT. In particular, patients with low Ret-He who don’t respond to iron therapy should be examined for β-TT.

scholarly journals Diagnostic performance of hematological discrimination indices to discriminate between βeta thalassemia trait and iron deficiency anemia and using cluster analysis: Introducing two new indices tested in Iranian population

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mina Jahangiri ◽  
Fakher Rahim ◽  
Amal Saki Malehi
Keyword(s):  
Cluster Analysis ◽  
Iron Deficiency ◽  
Diagnostic Accuracy ◽  
Iron Deficiency Anemia ◽  
Diagnostic Performance ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Thalassemia Trait ◽  
Accuracy Measures ◽  
Good Diagnostic Accuracy

AbstractAlthough the discrimination between β-thalassemia trait (βTT) and Iron deficiency anemia (IDA) is important clinically, but it is challenging and normally difficult; so if a patient with IDA is diagnosed as βTT, then it is deprived of iron therapy. This study purpose was to evaluate the 26 different discriminating indices diagnostic function in patients with microcytic anemia by using accuracy measures, and also recommending two distinct new discriminating indices as well. In this study, 907 patients were enrolled with the ages over 18-year-old with either βTT or IDA. Twenty-six discrimination indices diagnostic performance presented in earlier studies, and two new indices were introduced in this study (CRUISE index and index26) in order to evaluate the differential between βTT and IDA by using accuracy measures. 537 (59%) patients with βTT (299 (56%) women, and 238 (44%) men), and also 370 (41%) patients with IDA (293 (79%) women, and 77 (21%) men) were participated in this study for evaluating the 28 discrimination indices diagnostic performance. Two new introduced indices (CRUISE index and index26) have better performance than some discrimination indices. Indices with the amount of AUC higher than 0.8 had very appropriate diagnostic accuracy in discrimination between βTT and IDA, and also CRUISE index has good diagnostic accuracy, too. The present study was also the first cluster analysis application in order to identify the homogeneous subgroups of different indices with similar diagnostic function. In addition, new indices that offered in this study have presented a relatively closed diagnostic performance by using cluster analysis for the different indices described in earlier studies. Thus, we suggest the using of cluster analysis in order to determine differential indices with similar diagnostic performances.

Frequency and types of hemoglobinopathies in children with microcytic anemia

2020 ◽  
pp. 1-10
Author(s):  
Sabeen Khan ◽  
Sahira Aaraj ◽  
Syeda Namayah Fatima Hussain
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anaemia ◽  
Health Centre ◽  
Thalassemia Major ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Antenatal Screening ◽  
Microcytic Anaemia ◽  
Deficiency Anaemia ◽  
Thalassemia Trait

Abstract Objective: To study the frequency and types of haemoglobinopathies in children with microcytic anaemia. Method: The prospective study was conducted at the Paediatric Out-patient Department of Shifa Falahi Community Health Centre, Islamabad, Pakistan, from July to December, 2018, and comprised patients aged from 3 months to 14 years who had haemoglobin <10mg/dl and mean corpuscular volume <70fL. Serum ferritin and haemoglobin electrophoresis were done to check for iron deficiency anemia and haemoglobinopathies. Data was analysed using SPSS 23. Results: Of 175 subjects, 33(18.9%) had haemoglobinopathies and 142(81.1%) had iron deficiency anaemia. Thalassemia trait 18(10.3%) was the leading cause amongst haemoglobinopathies, followed by thalassemia major 8(4.6 %) and intermedia 5(2.9%). There were 2(1.1%) patients with haemoglobin D. Conclusion: The prevalence of hemoglobinopathies was high. Identification of haemoglobinopathies is important for proper treatment, antenatal screening and future genetic counselling. Key Words: Haemoglobinopathy, Iron deficiency anaemia, Microcytic, MCV, IDA.

scholarly journals Red cell cytogram in CELL-DYN® Sapphire: a ready-to-use function for recognizing thalassemia trait

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Eloísa Urrechaga ◽  
Ohiane Boveda ◽  
Johannes J.M.L. Hoffmann
Keyword(s):  
Iron Deficiency ◽  
Visual Inspection ◽  
Numerical Data ◽  
Hemoglobin Concentration ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Red Cell ◽  
Optical Analysis ◽  
Presumptive Diagnosis ◽  
Thalassemia Trait

<p>Single-cell optical analysis of red blood cells provides information on the cellular hemoglobin concentration and volume of red cells. We evaluated the reliability of the typical profiles of the cytogram hemoglobin concentration/ volume (Mie Map), produced by the CELL-DYN<sup>®</sup> Sapphire analyzer (Abbott Diagnostics, Santa Clara, CA, USA) in the discrimination of iron deficiency anemia (IDA) and thalassemia trait. A total of 380 patients with microcytic anemia were studied: 220 with IDA, 101 β-thalassemia trait, 30 β-thalassemia trait with concomitant iron deficiency, 29 α-thalassemia trait. Three professionals reviewed the Mie maps, with no information regarding the disease of the patient. The observers made a presumptive diagnosis (genetic or acquired anemia) and the percentages of correct classifications were recorded. IDA showed broad shaped shift of the cytogram while carriers presented narrow clustering in the lower microcytic area: 100 % IDA were correctly classified and 96-82% of carriers were recognized. Visual inspection of the Mie map reveals different profiles in IDA and thalassemia trait; those patterns are in concordance with the numerical data Mie map helps in the evaluation of large amounts of data.</p><p> </p><p>红细胞单细胞光学分析提供了关于细胞血红蛋白浓度及红细胞体积的信息。 我们评价了典型的细胞图血红蛋白浓度/体积分布（Mie Map）在缺铁性贫血（IDA）和地中海贫血特征的识别方面的可靠性，分布曲线由CELL-DYN® Sapphire分析仪（Abbott Diagnostics, Santa Clara, CA, USA）生成。 一共对380例小细胞性贫血进行了研究：220例患有IDA，101例β有地中海贫血特征，30例β有地中海贫血特征合并缺铁性，29 α例地中海贫血特征。 由三名专业人员在没有任何患者病情信息的情况下进行Mie map读图。 读图者作出初步诊断（遗传性或获得性贫血），记录正确分类的百分比。 IDA表现出细胞图较宽发散形状的偏移，而基因携带者在更低的小细胞区域呈现较窄的聚集：100%的IDA被正确分类，96-82%的基因携带者得到确认。 Mie map的目测检查揭示了IDA和地中海贫血特征方面不同的分布；这些模式与数值数据相一致。Mie map有助于大量数据的评估。</p>

scholarly journals Comparison of red cell distribution width and a red cell discriminant function incorporating volume dispersion for distinguishing iron deficiency from beta thalassemia trait in patients with microcytosis

1996 ◽  
Vol 114 (5) ◽  
pp. 1265-1269 ◽  
Author(s):  
Carmen Silvia Passos Lima ◽  
Aparecida Ribeiro de Carvalho Reis ◽  
Helena Zerlotti Wolf Grotto ◽  
Sara Teresinha Ollala Saad ◽  
Fernando Ferreira Costa
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Discriminant Function ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Beta Thalassemia ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width ◽  
Thalassemia Trait

The red cell distribution width (RDW), and another red cell discriminant function incorporating RDW (MCV² x RDW/Hgb x 100) were determined in a group of 30 patients with iron deficiency anemia, 30 patients with beta thalassemia trait, and 30 normal subjects. Both RDW and (MCV² x RDW/Hgb x 100) mean values were significantly higher in iron deficiency anemia than in beta thalassemia trait (p<0.001). Taking RDW equal or above 21.0 percent among microcytic anemia patients, we identified correctly 90.0 percent of patients with iron deficiency anemia. The sensitivity and specificity of the test were 90.0 percent (IC 95 percent: 0.75 - 0.96) and 77.0 percent (IC 95 percent: 0.60 - 0.88), respectively. RDW values below 21.0 percent identified correctly 77.0 percent of beta thalassemia trait with a sensitivity and a specificity of 77.0 percent (IC 95 percent: 0.60 - 0.88) and 90.0 percent (IC 95 percent: 0.75 - 0.96), respectively. Taking values of (MCV² x RDW/Hgb x 100) above and below 80.0 percent as indicative of iron deficiency and beta thalassemia trait, respectively, we identified correctly 97.0 percent of those patients in each group. Both sensitivity and specificity were 97.0 percent (IC 95 percent: 0.84 - 0.99). These results indicated that the red cell discriminant function incorporating volume dispersion (MCV² x RDW/Hgb x 100) is a highly sensitive and specific method in the initial screening of patients with microcytic anemia and is better than RDW in differentiating iron deficiency anemia from beta thalassemia trait.

scholarly journals ThalPred: a web-based prediction tool for discriminating thalassemia trait and iron deficiency anemia

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
V. Laengsri ◽  
W. Shoombuatong ◽  
W. Adirojananon ◽  
C. Nantasenamat ◽  
V. Prachayasittikul ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Nearest Neighbor ◽  
Laboratory Data ◽  
Model Performance ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Support Vector ◽  
Web Based ◽  
Thalassemia Trait

Abstract Background The hypochromic microcytic anemia (HMA) commonly found in Thailand are iron deficiency anemia (IDA) and thalassemia trait (TT). Accurate discrimination between IDA and TT is an important issue and better methods are urgently needed. Although considerable RBC formulas and indices with various optimal cut-off values have been developed, distinguishing between IDA and TT is still a challenging problem due to the diversity of various anemic populations. To address this problem, it is desirable to develop an improved and automated prediction model for discriminating IDA from TT. Methods We retrospectively collected laboratory data of HMA found in Thai adults. Five machine learnings, including k-nearest neighbor (k-NN), decision tree, random forest (RF), artificial neural network (ANN) and support vector machine (SVM), were applied to construct a discriminant model. Performance was assessed and compared with thirteen existing discriminant formulas and indices. Results The data of 186 patients (146 patients with TT and 40 with IDA) were enrolled. The interpretable rules derived from the RF model were proposed to demonstrate the combination of RBC indices for discriminating IDA from TT. A web-based tool ‘ThalPred’ was implemented using an SVM model based on seven RBC parameters. ThalPred achieved prediction results with an external accuracy, MCC and AUC of 95.59, 0.87 and 0.98, respectively. Conclusion ThalPred and an interpretable rule were provided for distinguishing IDA from TT. For the convenience of health care team experimental scientists, a web-based tool has been established at http://codes.bio/thalpred/ by which users can easily get their desired screening test result without the need to go through the underlying mathematical and computational details.

scholarly journals Iron Deficiency and Erythropoiesis: New Diagnostic Approaches

2003 ◽  
Vol 49 (10) ◽  
pp. 1573-1578 ◽  
Author(s):  
Carlo Brugnara
Keyword(s):  
Chronic Disease ◽  
Iron Deficiency ◽  
Transferrin Saturation ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Anemia Of Chronic Disease ◽  
Body Iron ◽  
Iron Stores ◽  
Human Erythropoietin ◽  
Iron Deficient

Abstract Iron deficiency anemia is one of the most common diseases worldwide. In the majority of cases, the presence of hypochromic microcytic anemia and biochemical evidence for depletion of body iron stores makes the diagnosis relatively straightforward. However, in several clinical conditions, classic biochemical indices such as serum iron, transferrin saturation, and ferritin may not be informative or may not change rapidly enough to reflect transient iron-deficient states (functional iron deficiency), such as the ones that develop during recombinant human erythropoietin (r-HuEPO) therapy. The identification and treatment of iron deficiency in settings such as r-HuEPO therapy, anemia of chronic disease, and iron deficiency of early childhood may be improved by the use of red cell and reticulocyte cellular indices, which reflect in almost real time the development of iron deficiency and the response to iron therapy. In the anemia of chronic disease, measurements of plasma cytokines and iron metabolism regulators such as hepcidin (when available) may be helpful in the characterization of the pathophysiologic basis of this condition. The ratio of serum transferrin receptor (sTfR) to serum ferritin (R/F ratio) has been shown to have excellent performance in estimating body iron stores, but it cannot be used widely because of the lack of standardization for sTfR assays. The combination of hematologic markers such as reticulocyte hemoglobin content, which decreases with iron deficiency, and R/F ratio may allow for a more precise classification of anemias.

Discriminant indices for distinguishing thalassemia and iron deficiency in patients with microcytic anemia: a meta-analysis

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
Johannes J.M.L. Hoffmann ◽  
Eloísa Urrechaga ◽  
Urko Aguirre
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Meta Analysis ◽  
Diagnostic Odds Ratio ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Extensive Literature ◽  
Discriminant Index ◽  
Extensive Literature Search ◽  
Thalassemia Trait

AbstractMore than 40 mathematical indices have been proposed in the hematological literature for discriminating between iron deficiency anemia and thalassemia trait in subjects with microcytic red blood cells (RBCs). None of these discriminant indices is 100% sensitive and specific and also the ranking of the discriminant indices is not consistent. Therefore, we decided to conduct the first meta-analysis of the most frequently used discriminant indices.An extensive literature search yielded 99 articles dealing with 12 indices that were investigated five or more times. For each discriminant index we calculated the diagnostic odds ratio (DOR) and summary ROC analysis was done for comparing the performance of the indices.The ratio of microcytic to hypochromic RBCs (M/H ratio) showed the best performance, DOR=100.8. This was significantly higher than that of all other indices investigated. The RBC index scored second (DOR=47.0), closely followed by the Sirdah index (DOR=46.7) and the Ehsani index (DOR=44.7). Subsequently, there was a group of four indices with intermediate and three with lower DOR. The lowest performance (DOR=6.8) was found for the RDW (Bessman index). Overall, the indices performed better for adults than for children.The M/H ratio outperformed all other discriminant indices for discriminating between iron deficiency anemia and thalassemia trait. Although its sensitivity and specificity are not high enough for making a definitive diagnosis, it is certainly of value for identifying those subjects with microcytic RBC in whom diagnostic tests for confirming thalassemia are indicated.

Red Blood Cell Distribution Width in Pediatric Microcytic Anemias

PEDIATRICS ◽  
1987 ◽  
Vol 80 (2) ◽  
pp. 251-254 ◽  
Author(s):  
Robert W. Novak
Keyword(s):  
Iron Deficiency ◽  
Normal Values ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Normal Children ◽  
Distribution Width ◽  
Age Appropriate ◽  
Pediatric Populations ◽  
Thalassemia Trait ◽  
Better Than

The RBC distribution width has been reported to be of value in the discrimination of iron deficiency anemia from other microcytic anemias, but studies in pediatric populations are lacking. A population of 734 normal children was studied to establish age-appropriate normal values for RBC distribution width. The RBC distribution width of 47 patients with microcytic anemia was then evaluated. RBC distribution width was elevated in 19 of 22 patients with iron deficiency but was also increased in six of 14 patients with thalassemia trait and two of 11 patients with anemia secondary to inflammatory disease. The resulting discrimination was better than that obtained by using Mentzer's index or the discriminant function in the patients studied. The RBC distribution width, albeit a less then perfect tool, can be of value in evaluating pediatric patients with microcytic anemia.

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