What causes elevated Mean Corpuscular Volume (MCV)?

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From the Guidelines

Elevated Mean Corpuscular Volume (MCV) is primarily caused by macrocytic anemias, vitamin deficiencies, and certain medications or conditions, with the most common causes including vitamin B12 and folate deficiencies, as indicated by the European Consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1. The causes of elevated MCV can be broken down into several categories, including:

  • Macrocytic anemias, which are characterized by larger than normal red blood cells
  • Vitamin deficiencies, such as vitamin B12 and folate deficiencies, which impair DNA synthesis and lead to larger red blood cells 1
  • Certain medications, such as methotrexate, which can interfere with DNA synthesis and cause macrocytosis, as recommended by the British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016 1
  • Conditions like alcoholism, liver disease, and hypothyroidism, which can also elevate MCV
  • Reticulocytosis, or an increase in immature red blood cells, which can naturally elevate MCV
  • Laboratory errors, such as prolonged storage of blood samples before testing, which can artificially increase MCV values When elevated MCV is detected, further testing, including vitamin B12 and folate levels, liver function tests, thyroid studies, and possibly bone marrow examination, may be necessary to determine the underlying cause, as suggested by the European Consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1.

From the Research

Causes of Elevated MCV

Elevated Mean Corpuscular Volume (MCV) is a condition where the average volume of red blood cells is higher than normal. The causes of elevated MCV can be classified into several categories:

  • Megaloblastic anemia, which is caused by deficiency or impaired utilization of vitamin B12 and/or folate 2
  • Nonmegaloblastic macrocytic anemia, which is caused by various diseases such as:
    • Myelodysplastic syndrome (MDS) 2
    • Liver dysfunction 2
    • Alcoholism 2
    • Hypothyroidism 2
    • Certain drugs 2
    • Inherited disorders of DNA synthesis 2
  • Vitamin B12 deficiency, which can lead to neurological deficits and is associated with an increased MCV 3, 4, 5, 6
  • Folate deficiency, which can also cause elevated MCV 4, 5

Association with Other Conditions

Elevated MCV has been associated with several other conditions, including:

  • Multiple sclerosis, where patients may have low serum vitamin B12 and folate levels and high levels of homocysteine 6
  • Pregnancy, where an MCV cutoff of 93.1 can correctly identify abnormal vitamin B12 levels with 81% sensitivity and 77% specificity 3
  • Aging, where the prevalence of macrocytic anemia may increase due to the growing older population 2

Diagnostic Value of MCV

The diagnostic value of MCV in detecting vitamin B12 deficiency is limited, with a sensitivity of 17-77% depending on the population studied 4. Therefore, MCV should not be used as the only parameter to rule out vitamin B12 deficiency, and further evaluation is necessary to confirm the diagnosis.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis and treatment of macrocytic anemias in adults.

Journal of general and family medicine, 2017

Research

Assessing mean corpuscular volume as a screening tool for gestational vitamin B12 deficiency based on NHANES.

International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition, 2024

Research

Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency.

Scandinavian journal of clinical and laboratory investigation, 2000

Research

Serum vitamin B12, folate, and homocysteine levels and their association with clinical and electrophysiological parameters in multiple sclerosis.

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2009

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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