Percentage of hypochromic erythrocytes and haemoglobin levels of reticulocytes - sensitive markers for functional iron deficiency diagnostics

Functional iron deficiency develops when the iron supply is insufficient for erythropoiesis (iron deficient erythropoiesis) despite sufficiently filled iron stores (normal or elevated ferritin).

This may lead to functional iron deficiency if

  1. sufficient existing iron from the stores cannot be made available quickly enough for the increased iron needs of stimulated erythropoiesis when there is high-dose therapy with recombinant erythropoietin,

  2. the iron, which is mainly stored in macrophages of the reticuloendothelial system, cannot be sufficiently mobilised because of an iron distribution disorder due to chronic diseases (infections, tumours, liver cirrhosis, alcoholism, autoimmune diseases, chronic renal insufficiency).

The early stages of iron deficient erythropoiesis cannot be reliably diagnosed with the usual haematological and biochemical markers for iron deficiency at the beginning of erythropoietin therapy or in cases of chronic inflammation or tumours.

Haematological parameters such as haemoglobin and the erythrocyte indices MCH and MCV are not sensitive enough. Changes do not become evident until after a period of some weeks.

Ferritin is an excellent marker of iron storage reserves, but as an acute phase parameter in inflammatory processes, it can mimic sufficient filling of the iron stores, falsely indicating that there is an adequate iron supply for erythropoiesis.

When interpreting transferrin values – similar to ferritin – any influence, including from acute and chronic inflammatory processes, needs to be taken into account.

Transferrin saturation, as a measure for transferrin iron loading and thus an indirect measurement of iron supply for erythropoiesis, is affected by the strong circadian fluctuations of serum iron.

The concentration of the soluble transferrin receptor has proven to be a good indirect marker of functional iron deficiency in chronic diseases. Its concentration increases when less iron is available for erythropoiesis. In hypoproliferative erythropoiesis, such as in renal anaemia, the concentration of the soluble transferrin receptor is reduced in spite of functional iron deficiency.

In addition to using the proven parameters of iron metabolism mentioned above, improved measurement technology with automated blood count determination has now made direct and highly sensitive diagnosis of the early stages of iron deficient erythropoiesis possible by calculating the haemoglobin content of the reticulocytes and the percentage of hypochromic erythrocytes, both during erythropoietin therapy in patients with chronic renal insufficiency as well as in iron distribution disorders.
If there is not enough iron available during erythropoietin therapy, this leads to a decrease in haemoglobin levels in the reticulocytes within 2 days. An increase in the percentage of hypochromic erythrocytes manifests itself within a week.

Both of these parameters therefore enable optimal adjustments between erythropoietin and iron to be made. Appropriate iron replacement therapy can improve therapy management and reduce costs.

Ret-Hb is measured in connection with determining the reticulocytes.
The percentage of hypochromic erythrocytes is determined in the context of full blood count testing.


  • Monitoring therapy in renal anaemia
  • Therapy optimisation for patients with chronic diseases
  • Early diagnosis of functional iron deficiency in pregnant women and small children

Reference ranges
Ret-Hb: > 29 pg
percentage of hypochromic red cells: < 5 %

Test material
3 ml of EDTA blood

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