This observation in my own blood counts brought about an interesting “case study” and eventually an investigation of the existing research and clinical importance of larger than normal red blood cells.

Red blood cell size is measured in mean corpuscular volume (MCV), which is part of a routine complete blood count (CBC).  Macrocytosis is the term used to describe larger than normal red blood cells,  defined as above the normal range of 80-96fL.  Although it is not a disease by itself, it may indicate other problems including vitamin B12 or folate deficiency, liver disease, or a range of other conditions.

Throughout high school and college I had periodic blood counts and my MCV consistently measured above 100fL, with the highest value of 104.5fL. Measures between 80-100fL are considered normal. However, since I had no other abnormal blood counts or symptoms, my abnormally high values were disregarded as a mystery.  However, through my research on iron regulation in runners I came across the phenomenon of runner’s macrocytosis.  The elevated red blood cell size that has been observed in runners is proposed to be caused by the destruction of red blood cells during footstrike. 

The mechanism of hemolysis

The hypothesis is that MCV is elevated because impact forces destroy more of the  older red blood cells and shift the proportion toward larger, younger cells and reticulocytes, which are immature red blood cells.  This is also referred to as runner’s hemolysis, footstrike hemolysis, or the misleading term of runner’s anemia (more on this later).  As I looked back on my training logs and blood count history, the progression of my MCV was consistent with my increase in training.

Hemolysis destroys more older cells, leading to a larger average size

Note that my MCV was never below the normal range of 80-96fL, even with iron deficiency anemia. MPW is a measure of running miles per week

The lack of literature on this topic is surprising and the most influential publications are case studies. One frequently cited case study describes the increasing MCV values of a 40 year old male recreational runner and is one of the first to characterize the phenomenon of runner’s macrocytosis due to hemolysis in 1985.  Blood indicators were tracked over eight years as the subject was training for marathons and logging an average of 45 mile weeks.  Over this time period, the MCV increased from 85fl to 96fL  accompanied by a decrease in hemoglobin.  

Another case study published as a Grand rounds report from Johns Hopkins, describes the evaluation of a woman with low hemoglobin, high MCV, but normal ferritin.  An extensive battery of tests was performed with no indication of pathology until the patient history revealed an exercise routine of running five miles every other day and eventually was given the “rare diagnosis” of runner’s anemia.

But how rare is this phenomenon? It is not isolated in case studies, as several larger cohort studies have noted this trend as well. One study I was involved in of 20 female collegiate runners revealed a significantly higher MCV in the runners compared to age and body matched controls with 41% of runners with MCV values over 95fL. This phenomenon is not isolated to runners as a study of aerobic dance instructors also showed a significant elevation over controls and and 33% had values over 95fL.

But is this considered runner’s anemia? Runner’s anemia is often used as an umbrella term to characterize changes in both MCV and hemoglobin. Ultimately, it is an ambiguous phenomenon and an instigator of confusion. So what does this actually mean? And does it matter that my cells are too big?

All valid questions to be answered in the following posts.