Basic yearly blood work generally includes a CBC, or a complete blood count. This gives a breakdown of red blood cells (their sizes and distributions), white blood cells and their subtypes, and platelets. It can offer clues to certain aspects of overall health.

One of the measurements pertaining to red blood cells is the MCV (Mean Corpuscular Volume). This is a measurement of the size of the red blood cell. When it’s too high, this is called macrocytosis (large red blood cells). When coupled with lower than normal hemoglobin levels, this becomes macrocytic anemia.

You can have macrocytosis without macrocytic anemia, though. Often, elevated MCV without anemia occurs along with high MCH (Mean Corpuscular Hemoglobin) and high MCHC (Mean Corpuscular Hemoglobin Concentration). These mean that there’s more hemoglobin stuffed into individual red blood cells than usual, because they’re bigger.

Causes of Macrocytosis (High MCV)

Most often, both macrocytosis and macrocytic anemia occur due to deficiency in Vitamin B12 or folate. Pernicious anemia is an autoimmune destruction of the cells that make Intrinsic Factor, necessary to absorb B12. Therefore, macrocytic anemia follows.

But if you’ve already tried supplementing B12 and folate, and macrocytosis persists, one likely cause is hypothyroidism. According to this paper, macrocytosis is found in up to 55% of hypothyroid patients, although all types of anemia can be associated with hypothyroidism. This is because thyroid hormone is necessary to stimulate the production of red blood cells. (Note that this doesn’t mean you have to actually be outside the lab reference range! If you have the symptoms of hypothyroidism and your levels are suboptimal, this can still be the cause.) 

Another possible, and common, cause is Non-Alcoholic Fatty Liver Disease (although fatty liver secondary to alcoholism will cause this as well). NAFLD is highly correlated with insulin resistance and metabolic syndrome. A fatty liver can lead to fibrosis, preventing the liver from doing its important job of detoxifying the chemicals you are exposed to on a regular basis. Two of the best markers on regular blood work for this are basic liver enzymes, and ferritin (elevation can imply a fatty liver). 

The Upshot:

If you have chronic macrocytosis and B12 and folate haven’t changed your numbers, consider asking your doctor to evaluate you for hypothyroidism. This means a full thyroid panel, not just TSH and total T4. Also consider evaluation for NAFLD. Both conditions are quite common.