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
1
are iron deficiency and thalassemia trait . 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 anemia 3. 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 anemia 6, 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 trait 3.
Qualitative and quantitative Hb analysis, preferably by HPLC rather than standard
electrophoresis, for identification of the amount and type of Hb present 8 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 traits 2,
9
.HbA2, however, can be falsely lowered by iron deficiency 10. 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 syndromes 11, 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 cost-effective
test that is performed using as little as one drop of capillary blood 13.

Thalassemia DNA gene detection by targeted mutation analysis 8 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
2010;5:11http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893117/?tool=pubmed

Dis,

9- Olivieri NF. The beta-thalassemias. N Engl J Med. 1999 Jul 8;341(2):99-109

10- Trent
RJ.
Diagnosis of
Feb;27(1):27-38.

the haemoglobinopathies. Clin

Biochem

Rev. 2006

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
14Cao
A
and
Galanello
2000.http://www.ncbi.nlm.nih.gov/books/NBK1426/

R,

Beta

thalassemia,