New diagnostics for iron deficiency based on the blood count

Due to the approximate life time of four months for erythrocytes in peripheral blood, iron deficits in erythropoiesis cannot be detected using classic haematological parameters such as Hb, MCV and MCH until a late stage.

However, modern haematology systems offer additional tests that are outstandingly suited to diagnosing and monitoring the therapy response in functional iron deficiency. These include determination of the percentage of hypochromic erythrocytes (%HYPO-He) and of the reticulocyte haemoglobin content (RET-He). Both parameters are recommended in the „European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure” in addition to the determination of transferrin saturation in this context.

Hypochromic erythrocytes (%HYPO-He) – „long-term parameter”
This parameter is regarded as having a good predictive value for the presence of iron deficient erythropoiesis extending back for more than the last 3 months. It determines the percentage of young and mature hypochromic erythrocytes containing less than 17 pg of haemoglobin equivalent. If the percentage of hypochromic erythrocytes (%HYPO-He) is greater than 2.7 %, then this indicates that there has been functional iron deficiency for a prolonged period of time.

Reticulocyte haemoglobin (RET He) – „short-term parameter”

While determining the number of reticulocytes, the preliminary stages of erythrocytes, allows for a prompt statement concerning the „quantity” of erythropoiesis in the bone marrow, the measurement of the haemoglobin content of the reticulocytes reflects the current iron supply for erythropoiesis and makes it possible to assess the „quality” of the cells. Changes in the iron status can therefore be detected much earlier. The reference range for RET He is approx. 28 to 35 pg. A value below 28 pg is indicative of iron deficiency.

Clinical chemical tests
Traditional biochemical markers for testing the iron status, such as serum iron, transferrin or ferritin, are so heavily influenced by factors like inflammation from an acute phase response that a clinical interpretation of the results is difficult or impossible.

Thus, factors such as low ferritin values unambiguously point to iron deficiency, while normal or elevated values do not permit any clear statements to be made without determining inflammation parameters (e.g. CRP). In chronic diseases – such as rheumatoid arthritis, but also liver damage, tumours and end-stage renal disease (dialysis patients) – ferritin levels may be increased in spite of iron deficiency.

In contrast, determining the serum iron is completely unsuitable for estimating a patient’s iron status. Besides major fluctuations within the course of a day and fluctuations from day to day, the reasons for this also include the strong decrease in the iron concentration when there is acute inflammation.

On the other hand, measuring the haemoglobin content of the reticulocytes (RET-He) as a „short-term parameter” and determining the hypochromic erythrocytes (%HYPO-He) as a „long-term parameter” shows whether sufficient iron is available for haemoglobin synthesis even in patients with chronic diseases.

Test material for hypochromic erythrocytes (%HYPO-He) and reticulocyte haemoglobin (RET-He)
1 small EDTA tube

Reference ranges
Hypochromic erythrocytes (%HYPO-He): < 2.7 %
Reticulocyte haemoglobin (RET-He): 28-35 pg (per cell)

The tests can also be requested for social health insurance patients (EBM).

Buttarello M. et al. (2010): Diagnosis of Iron Deficiency in Patients Undergoing Hemodialysis. Am J Clin Pathol 2010;133:949-954.
Urrechaga E. et al. (2011): Erythrocyte and reticulocyte parameters in iron deficiency and thalassemia. J Clin Lab Anal 25: 223–228.
Urrechaga E et al. (2011): The role of automated measurement of red cell subpopulations on the Sysmex XE-5000 analyzer in the differential diagnosis of microcytic anemia. Int J Lab Hematol 33: 30–36.
Urrechaga E et al. (2009): Potential utility of the new Sysmex XE 5000 red blood cell extended parameters in the study of disorders of iron metabolism. Clin Chem Lab Med 47: 1411–1416.

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