What is the workup for a patient with macrocytosis (Mean Corpuscular Volume (MCV) > 100)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: April 27, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

A high mean corpuscular volume (MCV) of 111 fL indicates macrocytosis and requires a systematic workup, starting with a thorough history and laboratory tests including complete blood count with peripheral smear, vitamin B12 and folate levels, thyroid function tests, liver function tests, reticulocyte count, and serum LDH, as recommended by the most recent guidelines 1. The workup for macrocytosis should focus on identifying the underlying cause, which can include vitamin B12 or folate deficiency, alcoholism, liver disease, myelodysplastic syndrome, and certain medications.

  • Key laboratory tests to order include:
    • Complete blood count with peripheral smear
    • Vitamin B12 and folate levels
    • Thyroid function tests
    • Liver function tests
    • Reticulocyte count
    • Serum LDH
  • Consider testing for methylmalonic acid and homocysteine levels if B12 deficiency is suspected despite normal serum B12, as suggested by 1 and 1.
  • The most common causes of macrocytosis are vitamin B12 or folate deficiency, alcoholism, liver disease, myelodysplastic syndrome, and certain medications, as noted in 1 and 1.
  • If B12 deficiency is confirmed, treat with cyanocobalamin 1000 mcg intramuscularly daily for one week, then weekly for one month, followed by monthly injections or high-dose oral supplementation (1000-2000 mcg daily), as recommended by 1.
  • For folate deficiency, prescribe folic acid 1-5 mg daily, as suggested by 1.
  • Address underlying causes such as alcoholism or medication effects, and consider hematology consultation for bone marrow examination to rule out myelodysplastic syndrome or other hematologic disorders if initial workup is negative, as recommended by 1.

From the Research

Workup of MCV 111

The workup of a mean corpuscular volume (MCV) of 111 involves several steps to determine the underlying cause of macrocytosis.

  • The most common etiologies of macrocytosis are alcoholism, vitamin B12 and folate deficiencies, and medications 2.
  • A peripheral smear can help differentiate between megaloblastic and non-megaloblastic anemia, with megaloblastic anemia characterized by macro-ovalocytes and hyper-segmented neutrophils 2, 3.
  • Vitamin B12 and folate levels should be checked to rule out deficiencies, as these are common causes of megaloblastic anemia 2, 3, 4.
  • A reticulocyte count can help differentiate between drug or alcohol toxicity and hemolysis or hemorrhage 2.
  • Other possible etiologies of macrocytosis include hypothyroidism, liver disease, and primary bone marrow dysplasias, such as myelodysplasia and myeloproliferative disorders 2, 4.

Diagnostic Approach

  • The diagnostic approach to macrocytosis involves a combination of laboratory tests and physical examination 2, 4.
  • The MCV value can help guide the diagnostic workup, but it should not be used as the sole criterion for ruling out certain etiologies 5.
  • A broader set of laboratory tests, including vitamin B12 and folate levels, reticulocyte count, and peripheral smear, should be used to determine the underlying cause of macrocytosis 2, 3, 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of macrocytosis.

American family physician, 2009

Research

Investigation of macrocytic anemia.

Postgraduate medicine, 1979

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.