Background. The two most frequent types of microcytic anemia are beta thalassemia trait (β-TT) and iron deficiency anemia (IDA). We retrospectively evaluated the reliability of various indices for differential diagnosis of microcytosis and β-TT in the same patient groups. Methods. A total of 290 carefully selected children aged 1.1–16 years were evaluated. We calculated 12 discrimination indices in all patients with hemoglobin (Hb) values of 8.7–11.4 g/dL. None of the subjects had a combined case of IDA and β-TT. All children with IDA received oral iron for 16 weeks, and HbA2 screening was performed after iron therapy. The patient groups were evaluated according to red blood cell (RBC) count; red blood distribution width index; the Mentzer, Shine and Lal, England and Fraser, Srivastava and Bevington, Green and King, Ricerca, Sirdah, and Ehsani indices; mean density of hemoglobin/liter of blood; and mean cell density of hemoglobin. Results. The Mentzer index was the most reliable index, as it had the highest sensitivity (98.7%), specificity (82.3%), and Youden’s index (81%) for detecting β-TT; this was followed by the Ehsani index (94.8%, 73.5%, and 68.3%, resp.) and RBC count (94.8%, 70.5%, and 65.3%). Conclusion. The Mentzer index provided the highest reliabilities for differentiating β-TT from IDA.

https://downloads.hindawi.com/journals/anemia/2014/576738.pdf

Hematological indices for differential diagnosis of Beta thalassemia trait and iron deficiency anemia.

Background More 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. Methods 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. Results 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. Conclusions 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.

https://www.degruyter.com/downloadpdf/j/cclm.2015.53.issue-12/cclm-2015-0179/cclm-2015-0179.xml

Discriminant indices for distinguishing thalassemia and iron deficiency in patients with microcytic anemia: a reply

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.

/pdf/the-role-of-automated-measurement-of-rbc-subpopulations-in-30d2dbyj71.pdf

The role of automated measurement of RBC subpopulations in differential diagnosis of microcytic anemia and β-thalassemia screening.

Background: % Microcytic and % hypochromic red cells show an inverse trend in b thalassemia trait and in iron deficiency anemia (IDA). The aim of this study was to assess the discriminant value of % microcytic/ % hypochromic ratio, as can be obtained from the Advia 2120 (Siemens) analyzer, in the differential diagnosis of microcytic anemia, compared to the conventional England and Fraser, Green and King, Mentzer, Ricerca, Shine and Lal and Srivastava indices. Methods: Receiver operating characteristic (ROC) curves, sensitivity, specificity and Youden index of indices were calculated for a set of 148 IDA patients and 170 b thalassemia carriers. Results: The Green and King index showed the best area under the curve (AUC, 0.962), with a Youden index of 80.9%; the % microcytic/% hypochromic ratio ranked second (AUC 0.943), with a Youden index of 76.3% and a sensitivity of 99.2%. Conclusions: This index, with high sensitivity for b thalassemia screening, can be a useful tool in the differential diagnosis of microcytic anemia, so samples can be chosen for HbA2 analysis, to confirm the presumptive diagnosis of the disease. As specificity is 77.1%, we assume it will be 22.9% for false positives, but these samples will have HbA2 values within the reference range, for correct diagnosis. Clin Chem Lab Med 2008;46:1752–8.

Discriminant value of % microcytic/% hypochromic ratio in the differential diagnosis of microcytic anemia.

BACKGROUND

Tuberculosis (TB) induces a systemic inflammatory state affecting iron homeostasis. Patients with TB often have additional comorbidities such as anemia which can result in poorer treat outcomes. We studied the contribution of anemia and the role of the iron regulatory hormone hepcidin among TB patients and household contacts.

METHODS

We analyzed serum samples from 102 TB cases and 98 controls without TB, matched by age/sex, for hepcidin, iron, and inflammation parameters. Five controls developed TB within 12 months. We used linear regression to assess associations.

RESULTS

Anemia of chronic disease (ACD) was more frequent among cases than controls (59.8% vs. 26.1%), but iron-deficiency anemia more frequent in controls (10% vs. 1%). The median hepcidin level was higher in cases than controls (63.7 vs. 14.2 ng/mL), but coinfections with HIV, helminths, and respiratory pathogens did not show cumulative effects. Hepcidin was associated with more severe TB symptom scoring (coefficient 0.8, 95% confidence interval [CI] 0.5-1.2) and higher mycobacterial load (0.7, 95% CI 0.4-1.0). Hepcidin was higher in TB cases and controls who developed TB compared to controls without TB (p<0.001), even when restricting to HIV-negative study participants.

CONCLUSIONS

ACD was the predominate etiology in TB patients suggesting limited benefit from iron supplementation. Increased hepcidin levels long before active disease, indicating altered iron metabolism, may be a marker for developing disease among TB-exposed individuals. Clinical management of anemia and nutrition interventions in TB patients need to be considered to improve the clinical course and outcomes.

/pdf/anemia-in-tuberculosis-cases-and-household-controls-from-17t0gi3zri.pdf

Anemia in tuberculosis cases and household controls from Tanzania: contribution of disease, coinfections, and the role of hepcidin

The present study aimed to retrospectively evaluate the usefulness of cell counter–based parameters and formulas in β-thalassemia trait (BTT) detection. The study included 170 BTT cases (hemoglobin [Hb]A 2 >4.0% [0.04]) and 30 non-BTT cases (HbA 2 , 2.3%3.5% [0.02-0.04]). Depending on the hemoglobin level and iron deficiency, the BTT group was further classified into classic BTT (n = 112) and BTT with iron deficiency anemia (n = 58). The RBC count, MCH, MCV, RDW, and Shine and Lal, Mentzler, Srivastava, England and Fraser, Ricerca, and Green indexes were applied. For the first time in the population of India, these 10 cell counter parameters and manual formulas were compared with high-performance liquid chromatography–derived HbA 2 levels for deriving a cost-effective alternative method; and receiver operating characteristic curves were applied. We found that the Shine and Lal, Srivastava, and Mentzler indexes, MCV, and MCH have better discriminative function than the RBC count and red cell distribution width and their related formulas. Thalassemia is a genetic disorder affecting synthesis of the globin moiety of the hemoglobin molecule. β-Thalassemia is prevalent in a broad belt extending from the Mediterranean basin to Southeast Asia. It is estimated that 1.5% of the world’s population carries β-thalassemia, ie, at least 80 to 90 million people with an estimated 60,000 new carriers born each year. The Southeast Asian region (which includes India, Thailand, and Indonesia) accounts for about 50% of the world’s carriers, ie, around 40 million people and almost half of homozygous births, whereas in the developed world, Europe and the Americas jointly account for just 10% to 13% of the world’s carriers. 1 The prevalence of β-thalassemia trait (BTT) is about 3.3% in India. In various parts of India, the prevalence of BTT is different: 6.5% in Punjab, 8.4% in Tamilnadu, 4.3% in south India, and 3.5% in Bengal. βThalassemia has a high prevalence in some communities, such as Sindhi, Luvana, Tribes, and Rajputs. The incidence of BTT in Gujarat is 10% to 15% in these communities, whereas the incidence in the general population is 2% to 3%. 2 Because a majority of people with BTT are asymptomatic, they may not be aware of their carrier state. BTT is associated with mild or no anemia but with reduced mean corpuscular volume (MCV) mean corpuscular hemoglobin (MCH) values and an elevated hemoglobin A 2 (HbA 2 ) level. The prevention of this homozygous condition can be

Usefulness of Cell Counter-Based Parameters and Formulas in Detection of β-Thalassemia Trait in Areas of High Prevalence

Platelet concentrates made from cell separators are used more frequently due to less donor exposure and leucodepletion. This retrospective study was done to compare plateletpheresis done on two cell separators: Baxter CS 3000 plus and Haemonetics MCS 3p. Plateletpheresis procedures, done from January 1997 to April 2002, were included in the study. One hundred and seven procedures were done on Haemonetics MCS 3p using SDP protocol, 49 procedures were done on Haemonetics MCS 3p using PLP protocol, and 107 were done on Baxter CS 3000 plus. Pre-procedure donor's platelet count and haemoglobin were comparable in all the groups. Platelet yield was comparable in PLP (6.44 x 10(11) platelets) and SDP (5.27 x 10(11)) protocols, but significantly less in Baxter (4.05 x 10(11) platelets, P < 0.001 for PLP and P < 0.05 for SDP). Efficiency of platelet removal was statistically significantly different in all the groups (P < 0.0001), however it was more in PLP (PLP-55.02%, SDP-47.38%, Baxter 38.98%). A significant number of products (19.51%) of Baxter failed to comply platelet count of product < or = 2,435 x 10(9)/l compared to 5.13% in PLP and 1.23% in SDP group; 36.96% of units from PLP and 28% from SDP qualified for split products compared to 1.18% of Baxter. PLP protocol of Haemonetics MCS 3p gives better platelet yield compared to Baxter CS 3000 plus and SDP protocol of Haemonetics MCS 3p.

Vinod Patel

Papers

Usefulness of Cell Counter-Based Parameters and Formulas in Detection of β-Thalassemia Trait in Areas of High Prevalence

Comparative study of plateletpheresis using Baxter CS 3000 plus and Haemonetics MCS 3P