What is the appropriate workup for anemia (iron deficiency disorder)?

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From the Guidelines

A comprehensive anemia workup should begin with a complete blood count (CBC) with differential, peripheral blood smear, reticulocyte count, and iron studies including serum iron, total iron binding capacity, ferritin, and transferrin saturation, as recommended by the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1. The workup should be guided by the patient's history, physical examination findings, and initial laboratory results. Anemia classification based on red cell size (microcytic, normocytic, macrocytic) and reticulocyte count (low versus high) helps narrow the differential diagnosis, as outlined in the Journal of the National Comprehensive Cancer Network study on cancer- and chemotherapy-induced anemia 1. Key considerations include:

  • Iron deficiency anemia, which typically presents with microcytic hypochromic cells and low ferritin
  • B12 or folate deficiency, which causes macrocytic anemia
  • Chronic disease anemia, which shows normal-sized cells with low iron but normal or elevated ferritin
  • Hemolytic anemias, which present with elevated reticulocyte counts and markers of red cell destruction Additional tests should include:
  • Vitamin B12 and folate levels
  • Hemoglobin electrophoresis if hemoglobinopathy is suspected
  • Direct antiglobulin test, haptoglobin, lactate dehydrogenase, and bilirubin levels for suspected hemolytic anemia
  • Kidney function tests, as renal disease can cause anemia, with a glomerular filtration rate (GFR) of less than 60 mL/min/1.73m2 indicating potential chronic kidney disease (CKD) 1 If the cause remains unclear, bone marrow examination may be necessary. Proper diagnosis is essential for targeted treatment of the underlying cause rather than simply supplementing iron or other nutrients. In patients with CKD, the investigation and management of anaemia is complex and requires consultation with specific guidelines relevant to UK practice published by NICE and the Renal association 1.

From the Research

Anemia Workup

  • The initial evaluation of suspected anemia consists of a thorough history and physical examination, as well as a complete blood cell count (CBC) 2
  • The CBC and mean corpuscular volume provide important clues to the classification and cause of anemia 2
  • Supplemental tests that may be included in the workup are:
    • Peripheral blood smear
    • Reticulocyte count
    • Iron panel (including ferritin and iron levels, total iron-binding capacity, and transferrin saturation)
    • Levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin 2
  • A logical approach to the clinical and laboratory evaluation of anemia is necessary, with the complete blood count and red cell indices offering clues to diagnosis 3
  • The reticulocyte count can serve as a useful screen for hemolysis or blood loss, and testing for specific causes of anemia should be performed 3
  • In some cases, examination of the bone marrow or molecular testing may be required to aid in the diagnostic process 3

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

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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