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Guide to interpretation of iron studies
MCQ: clinical scenario
MCQ: answer
MCQ: explanation
Guide to interpretation of iron studies
Iron studies are often ordered in the setting of suspected cases of iron deficiency or iron overload. Assessment of iron stores is helpful in the patient who presents with non specific symptoms of lethargy. Depending on the laboratory platform, assessment of iron studies includes measurement of:a). Serum iron.
Considerable variation occurs within a day in individuals and assessment of serum iron alone provides little helpful clinical information.
b). Serum transferrin (or total iron binding capacity; TIBC) / Transferrin saturation.
Iron is bound to transferrin in the plasma. Total iron binding capacity (TIBC) is a direct measure of level of transferrin. Transferrin levels are reduced in inflammation.
Level of transferrin saturation is particularly helpful if assessment of early stages of iron overload with levels > 55% for males and > 50% for females indicative of iron overload (should be fasting level for more accurate assessment).
c). Serum ferritin.
Small amount of circulating serum ferritin reflects body iron stores. Is now well established in assessment of iron stores.
Normal range 15 – 300 ug/l (reference ranges vary depending on the method used).
Levels < 15 ug/l reflect absent / reduced iron stores.
Elevated levels may reflect iron overload but will be increased in liver disease, inflammation or malignant disease. In the presence of inflammation, a level of > 100 ug/l generally excludes iron deficiency.
d). Soluble transferrin receptor.
Transferrin receptors are present on cell surfaces and are responsible for the internalization of transferrin resulting in intracellular release or iron. In the absence of adequate iron stores, expression of tranferrin receptors increases.
The amount of soluble transferrin receptor closely reflects iron stores and is not affected by the inflammatory process. Increased levels of soluble transferrin receptor are also found in conditions of increased red cell turnover (e.g. haemolysis).
Note: Interpretation of iron studies can be confusing with a number of the measures affected by iron therapy and acute phase response.
MCQ: clinical scenario
Consider these values.MCV: Decreased; Serum ferritin: Decreased; Total iron binding capacity: Increased; Serum iron: Decreased; Marrow iron: Absent
The most likely diagnosis is:
a) Thalassaemia trait
b) Hypoparathyroidism
c) Hereditary sideroblastic anaemia
d) Anaemia of chronic disease
e) Iron deficiency anaemia
MCQ: answer
The correct answer is E.MCQ: explanation
Iron deficiency anaemia or IDA is recognized from the combination of abnormal iron-supply studies and microcytic, hypochromic red blood cell morphology. The [serum iron] SI falls to very low levels [<4 mol/L (<30 g/dL)], while the total iron binding capacity [TIBC] increases. The ferritin level is always less than 15 g/L. Once the patient's hemoglobin level falls below 100 to 110 g/L (10 to 11 g/dL), poorly hemoglobinized cells begin to enter the circulation. When the anaemia is only of moderate severity, the cells tend to be microcytic but not hypochromic. At lower hemoglobin levels, both microcytosis and hypochromia become more pronounced. Furthermore, red blood cell production becomes increasingly ineffective, resulting in greater degrees of aniso- and poikilocytosis.With very severe iron-deficiency anaemia, cigar- or pencil-shaped red blood cells may be observed. As a rule, target cells are not seen with iron deficiency. When present, they suggest a globin chain production defect, i.e. one of the thalassemias. They may also be seen in the presence of liver disease.
The more common diagnostic problem is the potential confusion between iron deficiency and an inflammatory block in iron delivery from the reticuloendothelial system to the erythroid progenitors [the anaemia of chronic disease or AoCD]. However, while both the SI and TIBC decline in patients with AoCD, the TIBC is increased in iron deficiency anaemia while the SI is decreased. However, serum ferritin is increased in AoCD where it is decreased in iron deficiency anaemia and if a marrow aspiration is performed, AoCD will show normal to increased iron stores together with a hypoproliferative marrow morphology. Moreover, in anaemia of chronic disease [AoCD] patients typically show a low SI, low TIBC, a normal to high serum ferritin level.
Iron deficiency | Anaemia of chronic disease | Iron deficiency and inflammation | Acute phase response | Iron overload | |
---|---|---|---|---|---|
Serum iron | Decreased | Decreased | Decreased | Decreased | Increased |
Serum transferrin, Total iron binding capacity (TIBC) | Increased | Decreased | Decreased (low normal) | Decreased | Decreased or normal |
Transferrin saturation | Decreased | Decreased | Normal or decreased | Decreased | Increased |
Serum ferritin | Decreased | Normal (> 100 ug/l ) | “Normal” | Increased | Increased |
Soluble transferrin receptor | Increased | Normal | Increased | Normal | Decreased |
Also see the separate Q&A article, Interpretation of Iron Studies.
Reference(s)
1). Melbourne Haematology: A guide to interpretation of iron studies. Available online: http://www.melbournehaematology.com.au/pdfs/guidelines/melbourne-haematology-guidelines-iron-studies.pdf
2). UpToDate: Regulation of iron balance. Available online: https://www.uptodate.com/contents/regulation-of-iron-balance
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