Guideline for the laboratory diagnosis of functional iron deficiency.
Functional iron deficiency (FID) is a state in which there is insufficient iron incorporation into erythroid precursors in the face of apparently adequate body iron stores, as defined by the presence of stainable iron in the bone marrow together with a serum ferritin value within normal limits (Macdougall et al, 1989). In its broadest sense this definition encompasses the partial block in iron transport to the erythroid marrow seen in subjects with infectious, inflammatory and malignant diseases, and is a major component of the anaemia of chronic disease (ACD). One form of FID, found in some subjects treated with erythropoiesis-stimulating agents (ESAs), has been the subject of numerous studies following the widespread use of these agents, especially in subjects with chronic kidney disease (CKD).
The clinical assessment of iron status has largely been focussed on the level of iron stores, as reflected in the serum ferritin concentration. However iron in stores is metabolically inactive and is not only unavailable for immediate use but may be difficult to bring into use at all. The real clinical issue lies in active iron metabolism, the movement of iron from effete red cells and into further generations of developing red cells. It is nevertheless true that replenishment of iron lost from the red cell pool will be compromised and iron supply to the erythroid marrow will be suboptimal as iron stores become depleted. Irrespective of cause, inadequate iron supply leads to impaired haemoglobin production and a reduction in the mean cell haemoglobin (MCH) value that becomes apparent after several weeks of impairment. In contrast, it has long been evident that the adequacy of iron supply might be estimated from the haemoglobin content of the reticulocyte within a time span of a few days. With the widespread introduction of automated cell counters capable of measuring the numbers, volume and haemoglobin content of reticulocytes, many laboratories are now in a position to detect the early indications of a failure of iron supply in this way.
In 2006 the National Institute for Health and Clinical Excellence (NICE) published a guideline entitled, ‘Anaemia management in people with chronic kidney disease (CKD).’ (NICE, 2006). Among tests recommended for the assessment of iron status was the percentage of hypochromic red cells (%HRC). This variable, which continues to be recommended in the updated guideline (guideline 114, NICE, 2011), has limited availability, whilst the reticulocyte measures mentioned above have become more widely available. It is thus timely to review the use of these newer variables, together with more established measures of iron status, in the management of patients with FID.