Macrocytic and megaloblastic anemias
Macrocytic anaemia is when the red blood cells have a MCV >96fl. In reality there is one very common anemia from this group (megaloblastic anemia) and a few uncommon ones. We’ll talk about megaloblastic anemia first and then mention the less important ones after!
So, megaloblastic anemia is so called due to characteristic megaloblasts in the bone marrow. Megaloblasts are large, immature, and dysfunctional red blood cells (see image below). And there are a range of things that can cause megaloblastic anaemia.
The most common causes are Vitamin B12 (cobalamin), folate deficiency or less commonly, cytotoxic drugs. All three causes have the same mechanism of action, they lead to a defect in DNA synthesis along with alterations in RNA and protein synthesis. This expresses morphologically as larger-than-normal ‘immature’ nuclei with particulate chromatin.
Vitamin B12 is found in meat, salmon, cod, cheese, eggs and some fortified cereals. This means it is not uncommon in poorly managed vegetarians and vegans. It can also be caused by abnormal intragastric events (e.g. atrophic gastritis) that inhibit absorption. Severe B12 deficiency in the west is most likely to be caused by pernicious anemia.
Folate is found in greens, think broccoli, brussels sprouts, liver, leafy green veg, peas etc. deficits of folate are rarer than B12 in truth, but can be found in those with very unhealthy diets. Alcohol is a big causative factor of folate deficiency as it inhibits the intestinal absorption and transport of folate. Poor folate intake during pregnancy is another cause of megaloblastic anemia, as pregnancy and lactation require additional folate for growth of the fetus and maternal tissues. In the infant this can present as low-birthweight and midline deformities (neural tube defects, cleft lip etc). Other causes of low B12 include ileal resection and Crohn’s disease.
The clinical manifestation of megaloblastic anemia includes hematologic, cardiopulmonary, gastrointestinal, dermatologic (hyperpigmentation of the skin, premature graying), infertility, and psychiatric symptoms. B12 deficiency specifically has additional symptoms, including glossitis, angular cheilosis and a combination of pallor and mild jaundice leading to a ‘lemon tinge’. Patients may also develop neurological symptoms including extensor plantars, absent knee jerks and absent ankle jerks.