What is the appropriate workup and treatment for a 75-year-old female with macrocytic anemia?

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From the Guidelines

The workup for a 75-year-old female with macrocytic anemia, as indicated by an MCV of 105, MCH 34.9, RDW 11.5, and RBC 3.64, should prioritize the identification and treatment of vitamin B12 and folate deficiencies, with immediate treatment of vitamin B12 deficiency being crucial, especially if neurological involvement is suspected. The initial steps in the workup should include a complete blood count with peripheral smear, reticulocyte count, vitamin B12 and folate levels, thyroid function tests, liver function tests, and serum creatinine [ 1 ]. Given the potential for vitamin B12 deficiency to cause neurological symptoms, it is essential to assess for any sensory, motor, or gait symptoms, in which case urgent specialist advice from a neurologist and hematologist should be sought [ 1 ]. For the treatment of vitamin B12 deficiency without neurological involvement, hydroxocobalamin 1 mg intramuscularly should be administered three times a week for 2 weeks, followed by maintenance treatment with 1 mg intramuscularly every 2–3 months for life [ 1 ]. In cases of folate deficiency, after excluding vitamin B12 deficiency, oral folic acid 5 mg daily should be given for a minimum of 4 months [ 1 ]. Medication review is also crucial as certain drugs can affect folate and vitamin B12 levels, and addressing alcohol use, if applicable, is important [ 1 ]. Regular monitoring of complete blood counts and specific deficiencies is necessary to assess treatment response and adjust therapy accordingly, keeping in mind that some causes may require lifelong therapy.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Pernicious Anemia Parenteral vitamin B12 is the recommended treatment and will be required for the remainder of the patient's life.

WARNINGS Administration of folic acid alone is improper therapy for pernicious anemia and other megaloblastic anemias in which vitamin B12 is deficient.

The appropriate workup for a 75-year-old female with macrocytic anemia (indicated by an MCV of 105) would involve investigating the underlying cause of the anemia, with a focus on vitamin B12 deficiency.

  • The patient should be evaluated for pernicious anemia.
  • Schilling test may be considered to assess vitamin B12 absorption.
  • Folic acid deficiency should also be considered, but folic acid alone is not sufficient for treatment if vitamin B12 deficiency is present 2.
  • Treatment with parenteral vitamin B12 (e.g., cyanocobalamin) may be indicated, with an initial dose of 100 mcg daily for 6-7 days, followed by maintenance therapy 3.

From the Research

Initial Evaluation

The patient's laboratory results show an MCV of 105, MCH 34.9, RDW 11.5, and RBC 3.64, indicating macrocytic anemia. The initial evaluation should include:

  • A carefully obtained history and examination to identify potential causes of macrocytosis 4
  • Evaluation of a peripheral blood smear and reticulocyte count to guide further testing 4
  • Determination of the rate of development of anemia to provide diagnostic clues 5

Laboratory Testing

The following laboratory tests are recommended:

  • Serum vitamin B12 and folate levels to diagnose megaloblastic anemia 6, 4, 5
  • Serum thyroid studies to rule out hypothyroidism as a cause of macrocytosis 4
  • Liver function studies to evaluate for liver disease as a potential cause 4
  • Bone marrow aspirate and biopsy with cytogenetic analysis may be required to confirm a diagnosis suspected on the basis of the initial evaluation 4

Differential Diagnosis

The differential diagnosis for macrocytic anemia includes:

  • Megaloblastic anemia caused by deficiency or impaired utilization of vitamin B12 and/or folate 6
  • Nonmegaloblastic macrocytic anemia caused by various diseases such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, certain drugs, and inherited disorders of DNA synthesis 6
  • Other causes such as hemolysis or bleeding, exposure to chemotherapy, and primary bone marrow disorders 4

Treatment

Treatment of macrocytic anemia is cause-specific, and it is crucial to differentiate nonmegaloblastic from megaloblastic anemia 6. Vitamin B12 and folate deficiencies should be treated with replacement therapy, and underlying causes such as liver disease or hypothyroidism should be addressed 4, 5. If MDS is suspected, a hematology consultation may be appropriate 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of Anemia.

Obstetrics and gynecology clinics of North America, 2016

Research

Diagnosis and treatment of macrocytic anemias in adults.

Journal of general and family medicine, 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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