Review Question - QID 107667

A young, pregnant female presenting with symptoms of anemia without folate supplementation and with macrocytosis on her CBC likely has anemia due to folate deficiency. She should be treated with folate supplementation of at least 400 mcg daily.

Folate deficiency is a common cause of neural tube defects due to it's role in the development of the central nervous system. It has been reduced with the fortification of various foods (such as cereals and flour) with folate along with the folate supplementation for patients susceptible to deficiency (pregnant patients, alcoholics, etc). It most commonly presents with symptoms of anemia along with megaloblastic characteristics on peripheral blood smear (macrocytosis with neutrophils with 5 or more lobes). This occurs because, though RNA and protein synthesis allow the RBC membrane to grow, the lack of folate prevents DNA synthesis and replication.

Kaferle et al. discuss the evaluation of macrocytosis. They suggest the causes of megaloblastic anemia (demonstrated by macroovalocytes and hypersegmented neutrophils) to be most likely either vitamin B12 or folate deficiency. When the peripheral smear is non-megaloblastic, they suggest hypothyroidism, liver disease, medications (such as methotrexate, phenytoin, and bactim) and primary bone marrow dysplasias are other differentials to consider. When considering B12 or folate deficiency, they suggest using homocysteine levels (elevated in both) and methylmalonic acid levels (only elevated in B12 deficiency) to differentiate between the two, along with folate and B12 levels.

Crider et al. use a bayesian model to determine estimated RBC folate concentration at time of neural tube closure and risk of neural tube defects associated with various folate levels in a population in China. They determined that risk of neural tube defects was 25.4 (95% uncertainty interval 20.8 to 31.2) neural tube defects per 10,000 births at 500 nmol/L of folate and decreased as estimated RBC folate concentration increased. This decreased to 6 neural tube defects per 10,000 births at 1180 nmol/L of folate and was found to be consistent with the prevalence of neural tube defects in the US population before and after food fortification with folic acid.

Figure A is a peripheral blood smear demonstrating macrocytic RBCs with a neurophil with an 8-lobed nucleus, classifying this anemia as megaloblastic.

Incorrect Answers:
Answer 1 and 2: Iron deficiency anemia and thalassemia normally present with microcyctic, hypochromic anemias with possible target cells.
Answer 3: Vitamin B12 deificency presents with megaloblastic anemia, but is much less common than folate deficiency, especially in the setting of pregnancy.
Answer 4: Chronic diseases often cause anemia that is normocytic or microcytic.