What lab work should be ordered to confirm severe anemia and check for other issues?

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Laboratory Workup for Severe Anemia (Hemoglobin 6)

For a patient with severe anemia (hemoglobin 6 g/dL), a comprehensive laboratory workup should include iron studies, complete blood count with indices, reticulocyte count, and evaluation for other potential causes of anemia. 1, 2

Initial Laboratory Assessment

  • Complete blood count (CBC) with red cell indices to confirm the severity of anemia and provide clues to etiology 1, 2
  • Reticulocyte count to assess bone marrow response to anemia 1, 2
  • Iron studies including serum ferritin, transferrin saturation (TSAT), serum iron, and total iron-binding capacity (TIBC) 1
  • Serum bicarbonate to assess for metabolic acidosis, especially if chronic kidney disease is suspected 1
  • C-reactive protein to evaluate for inflammation that might affect interpretation of iron studies 2

Iron Deficiency Evaluation

  • Serum ferritin is the most useful single marker for iron deficiency; levels <30 μg/L confirm iron deficiency in the absence of inflammation 1
  • Transferrin saturation <16% suggests iron deficiency but should be interpreted alongside ferritin 1
  • In patients with inflammation, malignancy, or liver disease, ferritin may be falsely elevated; iron deficiency is unlikely if ferritin >100 μg/L 1
  • Consider a trial of iron therapy if iron deficiency is suspected despite equivocal lab results; a hemoglobin rise ≥10 g/L within 2 weeks strongly suggests iron deficiency 1

Additional Testing Based on Initial Results

  • If microcytic anemia (MCV <80 fL):

    • Hemoglobin electrophoresis to rule out hemoglobinopathies, especially in patients with appropriate ethnic background 1
    • Stool guaiac test to check for occult gastrointestinal bleeding 1
  • If normocytic anemia (MCV 80-100 fL):

    • Kidney function tests (BUN, creatinine) to evaluate for chronic kidney disease 1
    • Vitamin B12 and folate levels to rule out deficiencies that may mask microcytosis 3, 4
    • Thyroid function tests to rule out hypothyroidism 2
  • If macrocytic anemia (MCV >100 fL):

    • Vitamin B12 and folate levels 3, 4
    • Methylmalonic acid and homocysteine levels if B12 deficiency is suspected despite normal B12 levels 3
    • Liver function tests to evaluate for liver disease 2
  • If hemolysis is suspected:

    • Lactate dehydrogenase (LDH), haptoglobin, and bilirubin levels 2
    • Direct antiglobulin test (Coombs test) 5

Monitoring Parameters

  • For patients with chronic kidney disease (CKD):
    • Monitor hemoglobin at least every three months if GFR <30 ml/min per 1.73 m² 1
    • Check serum calcium, phosphorus, and intact parathyroid hormone (iPTH) levels 1
    • Monitor serum bicarbonate concentration at least every three months 1

Important Considerations

  • The severity of anemia (hemoglobin 6 g/dL) warrants urgent evaluation and may require blood transfusion based on symptoms and hemodynamic stability 2, 6
  • In men and post-menopausal women with iron deficiency anemia, gastrointestinal evaluation (upper endoscopy and colonoscopy) is recommended to rule out malignancy 1, 7
  • Avoid high-dose folic acid supplementation without ruling out B12 deficiency, as it may mask B12 deficiency symptoms while allowing neurological damage to progress 4
  • Consider bone marrow examination if the diagnosis remains unclear after initial testing, especially if multiple cytopenias are present 8

By following this systematic approach to laboratory evaluation, the underlying cause of severe anemia can be identified, allowing for appropriate targeted therapy to address both the anemia and its underlying etiology.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Anemia Diagnosis and Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnosis and Management of Pernicious Anemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Laboratory evaluation of anemia.

The Western journal of medicine, 1987

Research

Emergency Medicine Evaluation and Management of Anemia.

Emergency medicine clinics of North America, 2018

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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