31/12/2011 Distinguishing thalassemia trait from iron-deficiency

How to distinguish thalassemia carrier (trait) state from iron-deficient anemia By Dr Mohamed El Missiry The two main causes of microcytic and hypochromic anemia are iron deficiency and thalassemia trait1. Distinguishing between these conditions is important both for awareness and prevention of thalassemia and to avoid unnecessary iron therapy to thalassemia carriers. Both iron deficiency anemia and thalassemia will present with a normocytic hypocromic anemia (small red cells with low hemoglobin concentration) and hemoglobin is decreased in both types of anemia with values ranging from 9 to 11 g/dl in thalassemia minor2. In iron deficiency, complete blood counts (CBC) show MCV and MCH which are decreased proportionately to the degree of anemia, while in thalassemia trait they tend to be quite low even with moderate anemia3. Red cell distribution width (RDW) is high in iron deficiency anemia because there is a wide variation in red cell size while in mild thalassemia (alpha or beta) red cells tend to be more homogeneous and thus RDW is low4, 5. On blood smears, target-shaped cells are characteristic of thalassemia trait while are less frequent in iron deficiency anemia6, 1 In iron deficiency anemia, platelet counts may be slightly increased with counts >450,000/L6, 7. Serum iron, total iron binding capacity and serum ferritin are decreased in iron deficiency anemia while they are generally normal in thalassemia trait3. Qualitative and quantitative Hb analysis, preferably by HPLC rather than standard electrophoresis, for identification of the amount and type of Hb present8 is a very important test: elevated concentrations of the normal minor adult component of hemoglobin HbA2 (usually exceeding 3.5%) can be detected in thalassemia traits2, 9 .HbA2, however, can be falsely lowered by iron deficiency10. Fetal hemoglobin (HbF) is elevated in approximately 50 percent of cases, usually 1-3 % and rarely >5% 2. ZPP (zinc protoporphyrin) is recommended as a second test, in order to discriminate between microcytosis due to iron deficiency and thalassemia syndromes11, 12. ZPP/H ratio (zinc protoporphyrin/Heme ratio) is capable of predicting iron deficiency nearly as well as two or three laboratory tests combined, and by itself can detect pre-anemic deficiency better than other individual tests. Furthermore, ZPP/H ratio is a costeffective test that is performed using as little as one drop of capillary blood13.

Thalassemia DNA gene detection by targeted mutation analysis8 is the conclusive test, and it maybe justified when the gene mutation present in the family or ethinc group is unknown8, 14 In thalassemia-prone communities, carrier detection is very important to avoid overwhelming thalssemia diseased burden.

References 1- Han P, Fung KP. , Discriminant analysis of iron deficiency anaemia and heterozygous thalassaemiatraits: a 3-dimensional selection of red cell indices. Clin Lab Haematol. 1991;13(4):351-62. 2- Weatherall DG and Clegg JB. The thalassemia syndromes. 4th ed. Oxford, UK: Blackwell; 2001. 3- Hoffbrand AV, Moss PAH and Pettit IE Essential Haematology, 2006; 5th edition, Published by Blackwell Publishing Ltd. 4- http://www.pathologystudent.com/?p=2145 5- Harrington AM, Ward PC, Kroft SH. Iron deficiency anemia, beta-thalassemia minor, and anemia of chronic disease: a morphologic reappraisal. Am J Clin Pathol. 2008 Mar;129(3):466-71. 6- http://emedicine.medscape.com/article/202333-workup#a0756) 7- http://en.wikipedia.org/wiki/Iron_deficiency_anemia 8- Galanello R and Origa R, Beta-thalassemia, Orphanet J Rare Dis, 2010;5:11http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893117/?tool=pubmed 9- Olivieri NF. The beta-thalassemias. N Engl J Med. 1999 Jul 8;341(2):99-109 10- Trent RJ. Diagnosis of the haemoglobinopathies. Clin Biochem Rev. 2006 Feb;27(1):27-38. 11- Harthoorn-Lasthuizen EJ, Lindemans J, Langenhuijsen MM. Combined use of erythrocyte zinc protoporphyrin and mean corpuscular volume in differentiation of thalassemia from iron deficiency anemia. Eur J Haematol. 1998 Apr;60(4):24551.http://www.ncbi.nlm.nih.gov/pubmed/9579878 12- Sardn Estvez N, Herruer MH, Jansen R, Bergkamp FJ, Gorgels JP. Diagnostic value of zinc protoporphyrin in a screening strategy for alpha-thalassemia. Eur J Haematol.2009 May;82(5):393-7. Epub 2009 Jan 28.http://www.ncbi.nlm.nih.gov/pubmed/19187279

13- Yu KH. Effectiveness of zinc protoporphyrin/heme ratio for screening iron deficiency in preschool-aged children. Nutr Res Pract. 2011 Feb;5(1):40-5. Epub 2011 Feb 28.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061269/?tool=pubmed 14- Cao A and Galanello R, Beta thalassemia, 2000.http://www.ncbi.nlm.nih.gov/books/NBK1426/

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