Awanui Labs are changing the configuration of e-ordering to better reflect best practice and better utilisation of tests.
Iron studies will be available in the e-ordering system as follows:
- Ferritin only Iron studies without ferritin (ideally when the patient is well and off iron supplements).
- One or both can be ordered as outlined below.
- Serum ferritin is the most useful test used to assess body iron status in both primary care and inpatient settings.
For referrers using paper request forms:
- If available to you we would encourage to adopt e-ordering, this leads to less manual coding of tests into the laboratory information systems, less work and less chance for errors.
- If “iron studies” are ordered, then ferritin only will be performed, ideally when patient is otherwise well (no inflammatory illness and normal CRP) and not on iron replacement.
- If full iron studies are required, request the specific tests (iron, transferrin, transferrin saturation).
Background
Ferritin is a soluble 450kDa protein produced by the liver. It is found in all cells, providing an easily accessible intracellular iron store to support cellular function. In addition, ferritin is stored at higher concentrations in bone marrow macrophages, the spleen, and liver cells. Relatively small amounts are found in the serum in health, but the serum ferritin (SF) can increase quite rapidly, though transiently, in inflammation from ferritin release by the macrophages/reticuloendothelial cells. In health, SF is directly proportional to iron store levels, with 1 microgram/L of SF representing 8mg of stored iron. It is an accurate investigation to assess body iron stores.
Low ferritin always indicates iron deficiency, while high ferritin could be due to iron overload or many other causes. An example of the latter is the raised ferritin in inflammatory conditions, as ferritin is an acute phase protein. Useful tests in the further investigation of an unexpectedly raised serum ferritin is to exclude an acute phase (inflammatory) response such as performing a CRP, and to evaluate the serum transferrin saturation.
High serum ferritin levels with a normal transferrin saturation is commonly seen in primary care, most commonly caused by inflammation, liver, and renal disease. Less common causes include metabolic syndrome, malignancy, and haematological disorders with ineffective erythropoiesis.
If serum ferritin is unexpectedly high, and there is no history of transfusional iron overload, a high transferrin saturation (see cut-off levels below) >45% may point towards genetic haemochromatosis, particularly if there is a positive family history.
Genetic haemochromatosis is a relatively uncommon cause of high serum ferritin levels in non-Europeans. HFE haemochromatosis, the type seen in people of Western European ancestry, can be excluded in most cases by a normal transferrin saturation. There are, however, rare forms of genetic haemochromatosis, notably Type IV due to a ferroportin mutation that may present with a normal transferrin saturation. Please seek advice from a haematologist regarding this. The EASL guidelines recommend, if iron saturation is >45% and ferritin is >200ug/l in women; or if iron saturation is >55% and ferritin is >300ug/l in men, then testing for the hemochromatosis gene (HFE) is indicated. If iron saturation is raised but ferritin is normal on the first tests, then repeat the test ideally when the patient is well on a second occasion before considering testing for HFE. Ferritin is only required when monitoring patients with known haemochromatosis.
Ferritin is generally thought to be low if <30ug/l. However, mean ferritin levels depend upon age, sex, and ethnicity (Africans and Asians generally have higher ferritin levels). Marginally low or low ferritin in a male or post-menopausal woman that is otherwise unexplained, needs further investigation to determine a cause.
Other iron studies (transferrin and iron to calculate transferrin saturation) should only be performed when other causes of a raised transferrin (inflammation, acute and chronic liver disease, chronic kidney failure, and rarely in some types of neoplastic disease) are not present.
Iron studies should generally not be performed within three months of a blood transfusion or iron infusion as the results may cause confusion due to falsely elevated ferritin relative to body iron stores. Response to iron therapy is best judged by monitoring haemoglobin concentration. Ferritin monitoring is generally not required often, and usually no more often than every 6 months.
Iron saturation is decreased in iron deficiency and anaemia associated with anaemia of chronic inflammation. If anaemic, order full iron studies, and consider other causes (see below):
Suggested Tests in Different Clinical Situations
Dr Richard Steele
Chief Medical Officer
Awanui Labs