5. Physiologic roles of folic acid
• DNA synthesis, RNA synthesis, DNA methylation
• Folic acid play a critical role in DNA and RNA
synthesis.
• Folic acid deficiency can therefore impair DNA
synthesis, which in turn can cause a cell to arrest in
the DNA synthesis (S) phase of the cell cycle, make
DNA replication errors, and/or undergo apoptotic death
• Hematopoiesis
• Hematopoietic precursor cells are among the most
rapidly dividing cells in the body and hence are one of
the cell types most sensitive to abnormal DNA
synthesis.
6. • Two major effects of the deficiency on hematopoiesis
• Megaloblastic changes
• caused by slowing of the nuclear division cycle relative to the
cytoplasmic maturation cycle (ie, nuclear-cytoplasmic
dyssynchrony).
• Ineffective erythropoiesis
• occurs when there is premature death (eg, phagocytosis or
apoptosis) of the developing erythropoietic precursor cells in the
bone marrow .
• There may be hypercellularity of the bone marrow
• laboratory findings of hemolysis, including elevated serum iron,
indirect bilirubin, and lactate dehydrogenase (LDH), and low
haptoglobin.
• The reticulocyte count is typically low.
12. lnvestigations
• CBC and blood smear
• Anemia
• Macrocytic red blood cells (MCV >100 fL) or macro-ovalocytosis
• An MCV value >115 fL is more specific to vitamin B12 or folate
deficiency
• Mild leukopenia and/or thrombocytopenia
• Low reticulocyte count
• Hypersegmented neutrophils on the peripheral blood smear (ie, >5
percent of neutrophils with ≥5 lobes or ≥1 percent of neutrophils with
≥6 lobes)
• Increased lactate dehydrogenase
• Increased bilirubin
13. Peripheral smear and Bone marrow
Peripheral blood smear showing a
hypersegmented neutrophil (seven
lobes) and macroovalocytes, a pattern
that can be seen with vitamin B12
(cobalamin) or folate deficiency
Erythroid precursors in the bone marrow
(Left panel) Normal erythropoiesis.
(Right panel) Megaloblastic
erythropoiesis
.
14. • Serum folate measurement is very
sensitive to dietary intake; a single folate-
rich meal can normalise it in a patient with
true folate deficiency, whereas anorexia,
alcohol and anticonvulsant therapy can
reduce it in the absence of
megaloblastosis.
• For this reason, red cell folate levels are a
more accurate indicator of folate stores
and tissue folate deficiency.
15. Serum folic acid levels
• Above 4 ng/mL (above 9.1 nmol/L) – Normal.
• Suggests folate is not deficient, unless the individual has recently
consumed a folate-containing meal or supplement.
• In such cases, RBC folate can be obtained or prefer metabolite
testing .
• RBC folate more costly to obtain.
• From 2 to 4 ng/mL (from 4.5 to 9.1 nmol/L) – Borderline
Additional testing may be indicated depending on the clinical
circumstances and the degree of suspicion for folate deficiency.
• Below 2 ng/mL (below 4.5 nmol/L) – Low
• Consistent with folate deficiency.
• Values may be slightly higher in the first six months of life.
16. • MMA and homocysteine normal – No deficiency of
folate,vitamin B12.
• MMA and homocysteine elevated – Deficiency of
vitamin B12 (does not eliminate the possibility of folate
deficiency).
• MMA normal, homocysteine elevated – No
deficiency of vitamin B12. Consistent with deficiency of
folate.
• RBC folate — RBC folate is a surrogate for tissue
folate levels. RBC folate provides information about
folate status over the lifetime of RBCs, similar to
hemoglobin A1C for blood glucose levels.
• An RBC folate level below 150 ng/mL (<150 mcg/L;
<340 nmol/L) is consistent with folate deficiency as
long as there is not concomitant vitamin B12
deficiency (RBC folate is lower in individuals with
vitamin B12 deficiency).
17. Treatment of folate deficiency
• Oral folic acid 1 to 5 mg daily
• Duration
• Reversible cause of deficiency- one to four months or until there is
laboratory evidence of hematologic recovery.
• For those with a chronic cause of folate deficiency, such as chronic
hemolytic anemia - indefinitely.
• Intravenous folic acid indications
• Unable to take an oral medication (eg, due to vomiting or obtundation)
• Severe or symptomatic anemia
• Can partially reverse some of the hematologic abnormalities associated
with vitamin B12 deficiency .however, the neurologic manifestations of
vitamin B12 deficiency are not treated by folic acid.
• Thus, administration of folic acid to an individual with vitamin B12
deficiency can potentially mask untreated vitamin B12 deficiency or even
worsen the neurologic complications.
• Because of this, testing for (and treatment of) vitamin B12 deficiency
may be appropriate in certain patients being treated with folic acid
• Prevention of folate deficiency
• Enrich cereals and grain products with folic acid to reduce the risk of
neural tube defects.
18. Folic acid prophylaxis
• All women,from the moment they begin trying
to conceive until 12 weeks of gestation to
prevent neural tube defects
• Hemolytic anemias/hyperproliferative
hematologic states
• Patients with rheumatoid arthritis or psoriasis
on methotrexate
• Patients on antiepileptic drugs
• Patients with ulcerative colitis
