Diagnosis Scenario

You admit a well 75 year old woman with community-acquired pneumonia. She responds nicely to appropriate antibiotics but her haemoglobin remains at 100 g/l with a mean cell volume of 80. Her peripheral blood smear shows hypochromia, she is otherwise well, and is on no incriminating medications. You contact her GP and find out that her haemoglobin was 105 g/l 6 months ago. She has never been investigated for anaemia. You discuss this patient with your registrar and debate the use of ferritin in the diagnosis of iron deficiency anaemia. You admit to yourself that you are unsure how to interpret a ferritin result and how precise and accurate a serum ferritin is for diagnosing iron deficiency anaemia.

You therefore form the question, “In an elderly woman with hypochromic, microcytic anaemia, can a low ferritin diagnose iron deficiency anaemia?” You order a ferritin and head for the library (10 days later it comes back at 40 µg/l).

Searching Best Evidence on Disk with the single word “ferritin” yielded a very encouraging meta-analysis of 55 studies and a nice individual study, but your library didn’t carry either journal. You perform a MEDLINE search using the MeSH terms “ferritin” and “sensitivity and specificity” and find an article on diagnosing iron deficiency anaemia in the elderly published in a journal that your library does take
Am J Med 1990;88:205-9.

Read the article and decide:

  • Are the results of this diagnostic article valid?
  • Are the valid results of this diagnostic study important?
  • Can you apply this valid, important evidence about a diagnostic test in caring for your patient?

Completed Diagnosis Worksheet for Evidence-Based Gastroenterology and Hepatology

Citation

Guyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, Meyer R: Diagnosis of iron-deficiency anemia in the elderly.
Am J Med 1990;88:205-9.

Are the results of this diagnostic study valid?

Was there an independent, blind comparison with a reference (“gold”) standard of diagnosis?
Yes, they underwent bone-marrow aspirations.
Was the diagnostic test evaluated in an appropriate spectrum of patients (like those in whom it would be used in practice)?
Yes
Was the reference standard applied regardless of the diagnostic test result?
Yes

Are the valid results of this diagnostic study important?

Ferritin Iron Deficiency No Iron Deficiency Likelihood Ratio
≤ 45 70/85 15/150 8.2
> 45 ≤ 100 7/85 27/150 0.44
> 100 8/85 108/150 0.13
Totals 85 150
  • For pre-test probabilities in the 30-70% range, a ferritin < 45 would be very helpful, yielding post-test probabilities of 78-95% (in the latter case, a SpPin1).
  • In that same pre-test probability range, a ferritin > 100 would yield post-test probabilities of 5-23% (in the former case, a SnNout2).
    So it can give quite important results.

Can you apply this valid, important evidence about a diagnostic test in caring for your patient?

Is the diagnostic test available, affordable, accurate, and precise in your setting?
Needs to be assessed in each setting.
Can you generate a clinically sensible estimate of your patient’s pre-test probability (from practice data, from personal experience, from the report itself, or from clinical speculation)
Approximately 30%.
Will the resulting post-test probabilities affect your management and help your patient? (Could it move you across a test-treatment threshold?; Would your patient be a willing partner in carrying it out?)
Her result of 40 brings her post-test probability to 78%, certainly high enough for you to want to investigate her for causes of anaemia (GI loss, etc.).
Would the consequences of the test help your patient?
Yes, if it led to a reversible cause. But this would have to be weighed against early detection of an untreatable cause (e.g., cancer) that would simply take away “healthy” time. The options would need to be discussed with your patient.

Additional Notes

An excellent overview of 55 studies of lab tests for Fe-deficient anaemia: Guyatt et al:J Gen Intern Med 1992;7:145-53 (with a correction on page 423).

Anaemia: Diagnosis of iron deficiency anemia in the elderly

Clinical Bottom Line

In community dwelling elderly medical patients in whom iron deficiency anaemia is suspected, serum ferritin is a valid, precise diagnostic test.

Citation

Guyatt GH, Patterson CH, Ali M. Diagnosis of iron-deficiency anemia in the elderly.Am J Med 1990;88:205-9.

Clinical Question

In a patient with anaemia can a low serum ferritin be used to diagnose iron deficiency?

Search Terms

“ferritin” and “sensitivity and specificity” in MEDLINE

The Study

  • Gold Standard – bone marrow aspiration
  • Study setting – consecutive pts over the age of 65 yr. who were admitted with anaemia to a university-affiliated hospital in Canada.

The Evidence

Ferritin Iron Deficiency No Iron Deficiency Likelihood Ratio
≤ 45 70/85 15/150 8.2
> 45 ≤ 100 7/85 27/150 0.44
> 100 8/85 108/150 0.13
Totals 85 150

Comments

  • Excluded pts from institutions and pts who were “too ill” or had “severe dementia” although these were not defined.
  • Weighted kappa for bone marrow interpretation by 2 haematologists was 0.84.
  • Low values can SpPin, and high values can SnNout.
  • Also see the meta-analysis in J Gen Intern Med 1992;7:145-53. (with a correction on page 423).
Notes

  1. When a diagnostic test has a very high Specificity, a Positive result Rules-In the diagnosis. 
  2. When a diagnostic test has a very high Sensitivity, a Negative result Rules-Out the diagnosis.