Screening primary care patients for hereditary hemochromatosis with transferrin saturation and serum ferritin level: systematic review for the American College of Physicians

Ann Intern Med. 2005 Oct 4;143(7):522-36. doi: 10.7326/0003-4819-143-7-200510040-00011.


Background: Therapeutic phlebotomy for hereditary hemochromatosis is relatively safe and presumably efficacious when offered before cirrhosis develops, so screening primary care patients is of substantial interest.

Purpose: To conduct a systematic review of the evidence on 1) the prevalence of the disease in primary care, 2) the risk for morbid or fatal complications for untreated patients, 3) the diagnostic usefulness of transferrin saturation and serum ferritin level in identifying early disease, 4) the efficacy of early treatment, and 5) whether the benefits of screening outweigh the risks.

Data sources: MEDLINE search from 1966 through April 2004, complemented by reference review of identified original studies and review articles published in English.

Study selection: PubMed Clinical Queries filters search of prognosis, diagnosis, etiology, or treatment were used depending on the question. Two authors reviewed all titles and abstracts.

Data extraction: Two investigators independently reviewed extracted data.

Data synthesis: The prevalence of hereditary hemochromatosis was 1 in 169 patients to 1 in 556 patients (n = 3 studies). Uncontrolled, prospective studies of genetic homozygous patients did not consistently identify a link to overt hereditary hemochromatosis. A serum ferritin level less than 1000 microg/L was predictive of absence of cirrhosis. Six studies demonstrated reduced survival in patients with cirrhosis. Diagnostic studies varied with respect to case definition. No blinded, independent comparisons of screening tests with the gold standard (biopsy or results of quantitative phlebotomy) or randomized, controlled trials of phlebotomy were identified. Cost-effectiveness analysis was limited by lack of prospective data on the natural history of the disease.

Limitations: Varied case definition and lack of prospective cohort studies or randomized trials.

Conclusions: The available evidence does not demonstrate that benefits outweigh the risks and costs of screening for hemochromatosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Evidence-Based Medicine
  • Ferritins / blood
  • Genetic Testing*
  • Hematologic Tests
  • Hemochromatosis / diagnosis*
  • Hemochromatosis / epidemiology
  • Hemochromatosis / genetics*
  • Hemochromatosis / therapy
  • Humans
  • Phlebotomy
  • Prevalence
  • Primary Health Care
  • Risk Assessment
  • Sensitivity and Specificity
  • Transferrin / analysis


  • Transferrin
  • Ferritins