What labs should I order for a patient with severe anemia?

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Laboratory Tests for Severe Anemia Evaluation

For patients with severe anemia, a comprehensive laboratory workup should include complete blood count with red cell indices, reticulocyte count, iron studies (serum ferritin, transferrin saturation), vitamin B12, folate, inflammatory markers, and additional tests based on suspected etiology. 1

Initial Laboratory Assessment

  • Complete Blood Count (CBC) with red blood cell indices including:

    • Hemoglobin and hematocrit (to confirm and quantify severity of anemia) 1
    • Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH) (to classify anemia as microcytic, normocytic, or macrocytic) 1
    • Red Cell Distribution Width (RDW) (particularly helpful in distinguishing iron deficiency from thalassemia) 1, 2
  • Reticulocyte count to assess bone marrow response to anemia (low counts suggest inadequate production, high counts suggest hemolysis or blood loss) 1, 2

  • Iron studies - the cornerstone of anemia evaluation:

    • Serum ferritin (most specific test for iron deficiency; <30 μg/L confirms iron deficiency in absence of inflammation) 1, 2
    • Transferrin saturation (TSAT) (helps identify iron availability for erythropoiesis; particularly useful when ferritin may be falsely normal due to inflammation) 1, 2
    • Serum iron and total iron-binding capacity (TIBC) (complementary to ferritin and TSAT) 1

Additional Essential Tests

  • C-reactive protein (CRP) to assess for inflammation (important for interpreting ferritin levels) 1, 2

  • Vitamin B12 and folate levels to rule out deficiencies that may contribute to or cause anemia 1, 2

  • Differential blood cell count to assess for abnormalities in other cell lines that might suggest bone marrow disorders 1

Specialized Tests Based on Clinical Suspicion

  • Hemolysis panel if hemolytic anemia is suspected:

    • Lactate dehydrogenase (LDH) 1, 3
    • Haptoglobin 1, 3
    • Bilirubin (direct and indirect) 3
  • Hemoglobin electrophoresis if thalassemia or hemoglobinopathy is suspected, particularly in patients with microcytosis and normal iron studies 1

  • Percentage of hypochromic red cells and reticulocyte hemoglobin content if available (more sensitive markers of iron-restricted erythropoiesis) 1

  • Serum transferrin receptor levels may be helpful when ferritin levels are equivocal (46-99 μg/L) 4

Interpretation Guidelines

  • In patients with inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 1, 2
  • A combination of true iron deficiency and anemia of chronic disease is likely if ferritin is between 30-100 μg/L with inflammation 2
  • A good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) strongly suggests iron deficiency, even with equivocal iron studies 1

Clinical Pitfalls to Avoid

  • Misinterpreting normal ferritin in inflammatory states, which may be falsely elevated despite iron deficiency 1, 2
  • Failing to consider multiple causes of anemia, especially in elderly patients 5
  • Overlooking the need for GI evaluation in unexplained iron deficiency anemia, especially in men and postmenopausal women 5
  • Not recognizing that microcytosis and hypochromia can occur in conditions other than iron deficiency (thalassemia, sideroblastic anemia, anemia of chronic disease) 1

By following this systematic approach to laboratory testing, you can efficiently diagnose the cause of severe anemia and initiate appropriate treatment to improve patient outcomes.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Anemia Evaluation and Diagnosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Laboratory evaluation of anemia.

The Western journal of medicine, 1987

Research

Iron deficiency anemia.

American family physician, 2007

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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