Folic deficiency anemia is megaloblastic anemia caused by a violation of bone marrow hematopoiesis due to a deficiency of folic acid (vitamin B9). With folic deficiency anemia, all signs of anemic syndrome develop (pallor, weakness, tachycardia, decreased blood pressure), minor jaundice, enlarged spleen, anorexia, unstable stool. In order to confirm the diagnosis, a study of the hemogram, bone marrow, determination of the level of folic acid in red blood cells and blood serum is carried out. Treatment of B9-deficiency anemia requires folic acid replacement therapy.
D52 Folate deficiency anemia
Folic deficiency anemia is a complex of clinical and hematological manifestations caused by folic acid deficiency due to its limited intake, reduced absorption or increased expenditure. Folic deficiency anemia is less common than B12 deficiency, but it is often combined with the latter, and also often accompanies iron deficiency anemia. Folate deficiency anemia is particularly dangerous for pregnant women, since it can lead to the formation of malformations of the fetal nervous system, increase the risk of placental abruption, premature birth and the birth of a premature baby. This determines the urgency of the problem not only within the framework of hematology, but also pediatrics, obstetrics and gynecology.
Folic acid (vitamin Bc, B9) enters the body as part of folate compounds present in vegetables (legumes, broccoli, spinach, lettuce, asparagus), liver, meat, chocolate, yeast, etc. Folate reserves in the body are 5-10 mg, and the minimum daily need for them is 50 mcg (2-3 times higher during pregnancy). After stopping the intake of folic acid from the outside, the depletion of its endogenous reserves occurs in 3-5 months. Clinical manifestations of folate deficiency anemia develop with a decrease in the level of vitamin B9 in the blood serum of less than 4 ng/ml.
The etiology of folic deficiency anemia may be associated with insufficient exogenous intake of vitamin B9, impaired absorption in the intestine or increased excretion from the body. Most often, folic acid deficiency is alimentary in nature; it can be caused by unbalanced or insufficient nutrition, prolonged heat treatment of food, feeding children with goat’s milk, etc.
The increased need for folic acid is experienced by pregnant and lactating women, premature babies, adolescents, cancer patients, patients with hemolytic anemia, hemoblastosis, exfoliative dermatitis, psoriasis. These categories of people are at risk for the development of folate deficiency anemia.
Impaired absorption of folic acid in the gastrointestinal tract is observed in chronic alcoholism, a condition after extensive resection of the small intestine, celiac disease, intestinal lymphoma, Crohn’s disease, sprue, vitamin B12 deficiency, taking folate antagonists (anticonvulsants, barbiturates, oral contraceptives, etc.). Excessive excretion of folic acid from the body can contribute to liver cirrhosis, hemodialysis, heart failure.
Folic acid absorption occurs in the duodenum and the initial part of the jejunum. After entering the bloodstream, it binds to plasma proteins and is transported to the liver, where a significant part of folic acid is deposited in the depot, the rest is excreted in the urine.
Folic acid is present in the body in the form of a coenzyme form – tetrahydrofolic acid, which is actively involved in the synthesis of glutamic acid, pyrimidine and purine bases, as well as thymidine monophosphate, a component of DNA. With folic deficiency anemia, first of all, the synthesis of nucleic acids of actively dividing hematopoietic cells is disrupted, as a result of which normoblastic hematopoiesis is replaced by megaloblastic. The consequence of ineffective hematopoiesis is the development of anemia, combined with leukopenia and thrombocytopenia.
Folate deficiency anemia develops more often in young patients and pregnant women. Among the clinical manifestations, signs of anemic syndrome prevail: pallor of the skin with a hint of subictericity, weakness, tachycardia, arterial hypotension, dizziness.
Unlike pernicious anemia, with folic acid deficiency, neurological disorders (funicular myelosis) do not develop, and disorders of the gastrointestinal tract are not significantly expressed. Among the latter, anorexia, instability of the stool, atrophic gastritis, glossitis, minor splenomegaly are sometimes noted. With an in-depth examination, myocardiodystrophy may be detected.
In patients with epilepsy, schizophrenia, mental disorders, folic deficiency anemia exacerbates the course of the underlying disease. Folic acid deficiency during pregnancy is a risk factor for the formation of neural tube defects (anencephaly, hydrocephalus, meningocele), congenital heart defects, cleavage of the lip and palate (“cleft lip” and “cleft palate”), fetal hypotrophy. In addition, the pregnant woman increases the likelihood of miscarriage, bleeding, premature delivery.
After childbirth, women with folic deficiency anemia are more susceptible to the development of postpartum depression, and young children are more susceptible to delayed psychomotor development, impaired bowel function, and decreased immunity.
Blood test with folic deficiency anemia, hyperchromia, macrocytosis, leukopenia, thrombocytopenia, and a decrease in the number of reticulocytes are noted. Confirmation of the diagnosis is facilitated by the determination of a decrease in folic acid in blood serum (norm 6-20 ng / ml) and red blood cells (norm – 100-450 ng / l). The study of the myelogram reveals hyperplasia of the red germ, a megaloblastic type of hematopoiesis.
With folic deficiency anemia, the test with histidine taken orally turns out to be positive: the excretion of formiminglutamic acid in the urine increases significantly (>18 mg). With myocardiodystrophy, according to ECG data, there is a violation of the repolarization of the myocardium of the left ventricle. With the help of ultrasound of the abdominal organs, an increase in the spleen is determined. Folic deficiency anemia has to be differentiated from B12-deficient anemia, acute erythromyelosis, myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria, hypoplastic and autoimmune hemolytic anemia.
Treatment of folic deficiency anemia requires normalization of nutrition, elimination of provoking factors, and replacement therapy. Patients are prescribed oral folic acid at a dose of 1-5 mg per day for 4-6 weeks under the control of laboratory blood parameters. In therapy with vitamin B9 antagonists, its parenteral administration is prescribed. Patients with impaired folic acid absorption should be under the supervision of a hematologist and receive replacement therapy for life.
Pregnant women, patients with thalassemia, hemolytic anemia need preventive folic acid intake. In order to prevent fetal pathology and obstetric complications, folic acid intake of 0.4 mg / day should be started as part of pre-pregnancy preparation (several months before conception) and continued throughout pregnancy and breastfeeding. It is known that the prophylactic intake of folic acid, started before pregnancy, reduces the frequency of birth of children with congenital defects of the central nervous system by 3.5 times.
- American Society for Clinical Laboratory Science. Ten Things Physicians and Patients Should Question. — 2022.
- Long S., Goldblatt J. MTHFR genetic testing: Controversy and clinical implications // Australian Family Physician. — 2016. — № 4. — Р. 237–240.link
- Aisen P. S., Schneider L. S., Sano M. et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial // JAMA. — 2008. — № 15. — Р. 1774–1783. link
- Ilesanmi-Oyelere B. L., Kruger M. C. B vitamins and homocysteine as determinants of bone health: A literature review of human studies // J Hum Nutr Diet. — 2022. link
- Yuan H.-F., Zhao K., Zang Y. et al. Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis // Oncotarget. — 2017. — № 15. — Р. 24130–24141.link
- Bramanti E., Cicciu M., Matacena G. et al. Clinical Evaluation of Specific Oral Manifestations in Pediatric Patients with Ascertained versus Potential Coeliac Disease: A Cross-Sectional Study // Gastroenterol Res Pract. — 2014.link