Diagnosis

All about ferritin and iron studies.

Ferritin

Ferritin is the gold standard test that reflects total body iron stores. As the ferritin falls below approximately 50 μg/L the positive likelihood ratio for iron deficiency progressively increases above 1 (see Table 1). In a retrospective study at St. Michael’s Hospital, 90% of women were iron deficient in pregnancy.

Ferritin is an acute-phase reactant and levels can be elevated in the face of inflammation. In the absence of an active comorbidity and/or inflammation, a ferritin value >100 μg/L suggests adequate iron stores and a low likelihood of iron deficiency.

Table 1. Positive Likelihood ratio of serum ferritin for ID (Adapted from Guyatt et al, 1992)

Serum Ferritin Likelihood Ratio 95% Confidence Interval
≤15 μg/L 51.85 41.53-62.27
15 – 25 μg/L 8.83 7.22-10.44
25 – 35 μg/L 2.54 2.11-2.97
35 – 45 μg/L 1.83 1.47-2.19
45 – 100 μg/L 0.54 0.48-0.60
≥100 μg/L 0.08 0.07-0.09

A ferritin above 200μg/L is considered high. Elevated ferritin levels occur infrequently. In a retrospective study at St. Michael’ Hospital, only 3 out of 2400 (0.13%) ferritin tests ordered were levels above 200μg/L during pregnancy.

BOTTOM LINE: The prenatal multivitamin is not enough. Essentially every pregnant woman needs an additional iron supplement. A ferritin under 50µg/L suggests iron deficiency and almost every pregnant women is affected.

Guyatt GH, Oxman AD, Ali M, Willan A, McIlroy W, Patterson C. Laboratory diagnosis of iron-deficiency anemia – an overview. J Gen Intern Med 1992; 7:145–153.

Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 2005;352:1769-77.

Koperdanova, M., & Cullis, J. O. (2015). Interpreting raised serum ferritin levels. BMJ, 351, h3692.

What does a high ferritin mean?

A ferritin levels >200 μg/L in premenopausal women is considered elevated and may warrant further investigation. It is important to consider two broad etiologic categories:

  1. Raised ferritin without iron overload (i.e. inflammatory state) or,
  2. Raised ferritin due to iron overload. See Figure 1. These can usually be distinguished through a clinical assessment and a measure of transferrin saturation (TSAT).

Note – recent intravenous iron infusions (i.e. within the last 4 to 6 weeks) can temporarily raise ferritin levels to above 200μg/L. This is not true iron overload- and is no cause for concern.

Causes of high ferritin without iron overload:

  • Recent illness (such as an acute infection)
  • Excessive alcohol intake
  • Liver disease (such as hepatitis)
  • Acute or chronic inflammatory conditions (such as systemic lupus erythematosus)
  • Metabolic syndrome
  • Renal failure
  • Malignancy

Causes of high ferritin with iron overload:

  • Chronic blood transfusion for a red blood cell disorder
  • Inherited red blood cell disorder even in the absence of chronic transfusions (thalassemia major, thalassemia intermedia or sickle cell anemia NOT thalassemia minor/minima or sickle cell trait)
  • Hereditary hemochromatosis (very rare in premenopausal women)

Figure 1. Causes of high ferritin. (Adapted from Koperdanova & Cullis, 2015).

BOTTOM LINE: Do not worry about iron overload in pregnancy. Almost all pregnant women need iron – we suggest that you treat even before the ferritin test comes back.

Koperdanova, M., & Cullis, J. O. (2015). Interpreting raised serum ferritin levels. BMJ, 351, h3692.

Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 2005;352:1769-77.

When are additional iron studies needed?

Additional iron studies include serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT). They are only needed when ferritin levels are elevated (i.e. >200 μg/L ). There is no need to order iron studies regularly. Ferritin is the gold standard test for iron deficiency.

Do not worry about iron overload in pregnancy. Almost all pregnant women need iron – we suggest you to treat even before the ferritin test comes back.

BOTTOM LINE: Ferritin is the gold standard test for diagnosing iron deficiency.

Koperdanova, M., & Cullis, J. O. (2015). Interpreting raised serum ferritin levels. BMJ, 351, h3692.

Camaschella C. Iron-deficiency anemia. New England journal of medicine. 2015 May 7;372(19):1832-43.