CBC Biomarkers: Mean Corpuscular Volume (MCV)

Optimal Takeaways

The mean corpuscular volume (MCV) refers to the “average” size of red blood cells in circulation. The MCV is used to classify anemias that may be associated with large RBCs (macrocytic) as seen with folate or B12 deficiency and characterized by an elevated MCV, or small RBCs (microcytic) seen with iron deficiency and characterized by a decreased MCV.

The MCV may not reflect the presence of both very large and very small cells, which may average out to a normal MCV. Therefore, the red cell distribution width should be evaluated along with MCV.

Standard Range: 80 - 100 fL

The ODX Range: 82 - 89.9 fL

Low MCV is associated with iron-deficiency anemia, B6 deficiency (which may be caused by isoniazid), sideroblastic anemia, copper deficiency, thalassemia, malabsorption, blood loss, H. pylori infection, colorectal cancer, alcoholism, and lead poisoning. MCV may be low or normal in anemia of chronic disease, which can occur with diabetes, rheumatological disease, autoimmune disease, or malignancy (Cappellini 2015, Maner 2021).

High MCV is associated with pernicious anemia (B12 malabsorption), megaloblastic anemia due to B12 or folate deficiency, alcoholism, liver disease, myelodysplasia, elevated reticulocytes (Cappellini 2015), and hypothyroidism (Nagao 2017). A very high MCV of 101 fL or higher may be associated with hemochromatosis (Barton 2000). Medications that can increase MCV include phenytoin, azathioprine, and zidovudine (Pagana 2019).

Overview

The mean corpuscular volume reflects the average size or volume of a red blood cell. A decreased MCV indicates small or microcytic RBCs which occur with iron-deficiency anemia, sideroblastic anemia, or thalassemia. An increased MCV indicates the RBC is larger than normal and is considered macrocytic, a condition associated with megaloblastic anemia due to folate or B12 deficiency. Macrocytic non-megaloblastic anemia can be seen with hepatic insufficiency, chronic alcohol abuse, congenital Diamond-Blackfan anemia (Maner 2021), myelodysplastic syndrome, hypothyroidism, inherited orders of DNA metabolism, and certain drugs (Nagao 2017).

The mean corpuscular volume may be normal (normocytic) with anemia of chronic disease, chronic kidney disease, myelodysplasia, and mixed nutrient deficiencies such as both iron and folate or B12 deficiency, where some cells are small and some are large, creating a normal mean value (Cappellini 2015). Interestingly, in one evaluation of 9,645 NHANES participants, only 4.4% of those with serum B12 below 190 pg/mL (140 pmol/L) had an MCV above conventional range. However, 56.2% in this group had an elevated methylmalonic acid, a better indicator of B12 status than MCV (Wolffenbuttel 2020).

An increased mean corpuscular volume is associated with a number of dysfunctions, likely associated with nutrient insufficiencies. Cognitive decline was significantly greater in those with a higher MCV of at least 97 fL compared to those with a lower MCV of 91 fL or below (Gamaldo 2013).

Individuals with peripheral artery disease were found to have significantly higher MCV compared to controls i.e., 94 fL versus 90.9 fL. Higher MCV is also associated with elevated homocysteine, elevated gamma-glutamyl transferase, and compromised folate and B12 status, potential factors in peripheral artery disease (Mueller 2001).

In a large prospective study of individuals undergoing coronary angiography, incident all-cause mortality was low when MCV was below 89.8 fL and lowest at 86.7 fL or below (Anderson 2007).

A review of intensive care records revealed that a mean MCV of 89 fL was associated with survival in critical care myocardial infarction patients whereas a mean MCV of 91 fL was associated with mortality (Huang 2016).

References

Anderson, Jeffrey L et al. “Usefulness of a complete blood count-derived risk score to predict incident mortality in patients with suspected cardiovascular disease.” The American journal of cardiology vol. 99,2 (2007): 169-74. doi:10.1016/j.amjcard.2006.08.015

Barton, J C et al. “Screening for hemochromatosis in routine medical care: an evaluation of mean corpuscular volume and mean corpuscular hemoglobin.” Genetic testing vol. 4,2 (2000): 103-10. doi:10.1089/10906570050114786

Cappellini, M Domenica, and Irene Motta. “Anemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change With Aging?.” Seminars in hematology vol. 52,4 (2015): 261-9. doi:10.1053/j.seminhematol.2015.07.006

Gamaldo, Alyssa A et al. “Relationship between mean corpuscular volume and cognitive performance in older adults.” Journal of the American Geriatrics Society vol. 61,1 (2013): 84-9. doi:10.1111/jgs.12066

Huang, Yuan-Lan, and Zhi-De Hu. “Lower mean corpuscular hemoglobin concentration is associated with poorer outcomes in intensive care unit admitted patients with acute myocardial infarction.” Annals of translational medicine vol. 4,10 (2016): 190. doi:10.21037/atm.2016.03.42

Maner, Brittany S. and Leila Moosavi. “Mean Corpuscular Volume.” StatPearls, StatPearls Publishing, 10 July 2021.

Mueller, T et al. “Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study.” Angiology vol. 52,9 (2001): 605-13. doi:10.1177/000331970105200904  

Nagao, Takayo, and Makoto Hirokawa. “Diagnosis and treatment of macrocytic anemias in adults.” Journal of general and family medicine vol. 18,5 200-204. 13 Apr. 2017, doi:10.1002/jgf2.31                   

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Wolffenbuttel, B H R et al. “Association of vitamin B12, methylmalonic acid, and functional parameters.” The Netherlands journal of medicine vol. 78,1 (2020): 10-24.