What is the appropriate workup and treatment for anemia?

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Last updated: June 9, 2025View editorial policy

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From the Guidelines

The appropriate workup for anemia begins with a complete blood count (CBC) and peripheral blood smear to determine the type of anemia based on red cell indices (microcytic, normocytic, or macrocytic), as recommended by the most recent guidelines 1.

Initial Evaluation

The initial evaluation of anemia should include:

  • Complete blood count (CBC) and peripheral blood smear
  • Reticulocyte count to assess bone marrow response
  • Iron studies (serum iron, ferritin, total iron binding capacity)
  • Vitamin B12 and folate levels
  • Hemolysis markers if indicated

Diagnosis and Treatment

Treatment depends on the underlying cause of anemia.

  • For iron deficiency anemia, intravenous iron is recommended as first-line treatment in patients with clinically active inflammatory bowel disease (IBD), previous intolerance to oral iron, hemoglobin below 100 g/L, and in patients who need erythropoiesis-stimulating agents 1.
  • Oral iron supplementation may be used in patients with mild anemia, whose disease is clinically inactive, and who have not been previously intolerant to oral iron.
  • For B12 deficiency, cyanocobalamin 1000 mcg daily orally or intramuscularly for 1 week, then weekly for 4 weeks, followed by monthly maintenance is effective.
  • Folate deficiency requires folic acid 1 mg daily orally.
  • Severe anemia (hemoglobin <7 g/dL) or symptomatic patients may require blood transfusion.
  • Erythropoiesis-stimulating agents like epoetin alfa may be used for anemia of chronic disease or kidney disease.

Monitoring and Follow-up

Regular monitoring of hemoglobin levels and reticulocyte response is essential to assess treatment efficacy.

  • Re-treatment with intravenous iron should be initiated as soon as serum ferritin drops below 100 mg/L or hemoglobin below 120 or 130 g/L according to gender 1.
  • Addressing the underlying cause is crucial, whether it's occult bleeding, malabsorption, chronic disease, or bone marrow disorders.

Special Considerations

In patients with cancer, iron treatment should be given before the initiation of and/or during erythropoiesis-stimulating agent (ESA) therapy in the case of functional iron deficiency 1. In patients with IBD, the distinction between iron deficiency anemia and anemia of chronic disease is important, since both conditions typically overlap 1.

From the FDA Drug Label

• Evaluate iron status before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia before initiating treatment (2.1). The appropriate workup for anemia includes:

  • Evaluating iron status before and during treatment
  • Maintaining iron repletion
  • Correcting or excluding other causes of anemia before initiating treatment The treatment of anemia with epoetin alfa (SQ) involves:
  • Individualized dosing based on patient population (e.g. CKD, HIV, cancer) and response to treatment
  • Regular monitoring of hemoglobin levels and adjustment of dose as needed
  • Consideration of concomitant therapies (e.g. iron supplementation, blood transfusions) as needed 2 2

From the Research

Workup of Anemia

  • The workup of anemia involves a thorough history and physical examination, as well as laboratory tests such as a complete blood cell count (CBC) and peripheral blood smear 3.
  • The CBC and mean corpuscular volume provide important clues to the classification and cause of anemia 3.
  • Supplemental tests may include a reticulocyte count, iron panel, and levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin 3.

Diagnostic Approach

  • The diagnostic approach to anemia in primary care settings is focused on history, physical examination, laboratory findings, including complete blood cell count, reticulocyte count, and peripheral smear examination 4.
  • The evaluation of a patient with anemia includes clinical history, physical examination, and laboratory findings, with fecal occult blood test and abdominal ultrasound 4.
  • Anemia is classified and diagnosed by the values of hematological parameters, underlying pathological mechanism, and patient history 4.

Laboratory Tests

  • The first-line laboratory test for suspected anemia is the full blood count, which may suggest the anemia is caused by a nutritional deficiency of iron, vitamin B12, or folate 5.
  • Laboratory measurement of the concentration in blood of iron, vitamin B12, and folate, along with several other tests, are useful in the differential diagnosis of anemic patients 5.
  • The reticulocyte count serves as a useful screen for hemolysis or blood loss, and testing for specific causes of anemia is performed 6.

Treatment and Management

  • Treatment of iron deficiency anemia with oral iron can increase serum folate and vitamin B12 levels, even in patients with baseline low levels of serum vitamin B12 7.
  • Healthcare practitioners should be aware of the changes in metabolic pathways, including vitamin B12, folate, and lipids, that occur during iron therapy 7.
  • The mechanisms controlling these changes remain to be explained, but they are probably related to the control of iron homeostasis (iron deficiency mediated stimuli) 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anemia: Evaluation of Suspected Anemia.

FP essentials, 2023

Research

Anemia as a Problem: GP Approach.

Digestive diseases (Basel, Switzerland), 2022

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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