What is the initial laboratory workup for a new unexplained anemia?

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From the Guidelines

The initial laboratory workup for a new unexplained anemia should include a complete blood count (CBC) with differential, iron studies (serum iron, total iron binding capacity, ferritin), vitamin B12 and folate levels, and urinalysis or urine microscopy, as well as screening for coeliac disease (CD) serologically. This approach is based on the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1. The guidelines recommend taking a detailed history and initial investigation of confirmed iron deficiency anemia (IDA) should include urinalysis or urine microscopy, screening for coeliac disease (CD) and in appropriate cases, endoscopic examination of the upper and lower GI tract 1. Key points to consider in the initial laboratory workup include:

  • A detailed history to provide important clues as to the cause(s) of IDA
  • Initial investigation of confirmed IDA should include urinalysis or urine microscopy
  • Screening for coeliac disease (CD) serologically
  • Age, sex, Hb concentration and mean cell volume are all independent predictors of risk of GI cancer in IDA Some additional tests that may be considered include:
  • Reticulocyte count to assess bone marrow response
  • Thyroid function tests to rule out thyroid disorders
  • Hemoglobin electrophoresis to identify hemoglobinopathies
  • Direct Coombs test, lactate dehydrogenase (LDH), and haptoglobin to diagnose hemolytic anemias However, the most recent and highest quality study recommends prioritizing iron studies, vitamin B12 and folate levels, and urinalysis or urine microscopy, as well as screening for coeliac disease (CD) serologically 1.

From the Research

Initial Laboratory Workup for New Unexplained Anemia

The initial laboratory workup for a new unexplained anemia includes:

  • A complete blood cell count (CBC) to provide important clues to the classification and cause of anemia 2
  • Examination of the mean corpuscular volume to help classify the anemia 2
  • Supplemental tests such as:
    • Peripheral blood smear 2, 3
    • Reticulocyte count to serve as a useful screen for hemolysis or blood loss 2, 3
    • Iron panel (ie, ferritin and iron levels, total iron-binding capacity, transferrin saturation) 2
    • Levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin 2

Diagnostic Tests for Anemia

Diagnostic tests for anemia may also include:

  • Molecular testing to aid in the diagnostic process 3
  • Examination of the bone marrow, occasionally required for diagnosis 3
  • Serum ferritin, which is considered the gold standard for diagnosing iron deficiency anemia, with a specificity of 99% and sensitivity of 80% at a concentration of 30 ng/ml 4

Limitations of Certain Tests

It's worth noting that:

  • Serum iron and total iron binding capacity (TIBC) give no additional information in the diagnosis of iron deficiency anemia and are redundant if serum ferritin is available 4
  • Serum iron and TIBC have limited sensitivity and specificity, with values of 63.5% and 38.6% for serum iron, and 64.5% and 42.8% for TIBC, respectively 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anemia: Evaluation of Suspected Anemia.

FP essentials, 2023

Research

Anemia: Evaluation and Diagnostic Tests.

The Medical clinics of North America, 2017

Research

Diagnostic Accuracy of Serum Iron and Total Iron Binding Capacity (TIBC) in Iron Deficiency State.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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