MEGALOBLASTIC

ANEMIA
What is Megaloblastic anemia?
 Megaloblastic anemias are characterized
by the presence of abnormally large
developing red cells in the bone marrow.
 The marrow is usually cellular.
 Anemia is based on ineffective
erythropoiesis.
 These red cells are large in shape
Etiology
 Cobalamin: Deficiency / abnormal
metabolism.
 Folate: Deficiency / abnormal metabolism
/ antifolate drugs.
 Drugs interfering with synthesis of DNA.
 Rarely- orotic aciduria, AML,
myelodysplasia.
 Arsenic poisoning
 Nitrous oxide inhalation.
Cobalamin / Vitamin B12
Forms :
1. Ado (2-deoxyadenosyl) form; found in
mitochondria; Cofactor for Methyl Malonyl
CoA Mutase.
2. Methyl cobalamin; found in
plasma,cytoplasm; Cofactor for Methionine
synthase.
3. Hydroxocobalamin
Absorption

• Intrinsic
Active factor

Passive • buccal
• duodenal
1% • ileal
Absorption
Proteins involved in active absorption are,
◦ Intrinsic factor { IF=HCl }.
◦ Haptocorrins.
◦ Cubilin.
◦ Transcobalamin II.
◦ TC I – cobalamin analogues.
IFs are destroyed in illeal cells
Cobalamin enters portal blood after 6 hrs
of oral ingestion.
 Amount recirculated in bile 0.5 - 5µg.
 Body stores 2-3mg.
 Sufficient for 3-4 years without dietary
intake of cobalamin.
 Daily requirement: 1-3µg.
 Only traces are excreted in urine; in
pharmacological doses large part is
excreted in urine.
Causes of cobalamin defiency
 Nutritional –Vegans (legumes)
 Abnormalities - TC II deficiency; Congenital
absence of IF
 Malabsorption
Gastrectomy (total / partial)
Tropical sprue
Intestinal stagnant loop syndrome
Selective malabsorption
Ileal resection
Crohn’s disease
Pernicious anemia
Folate
 Destroyed easily by cooking especially in
large amounts of water.
 Storage in liver (sufficient for 3-4 months)
 Total body folate around 10mg.
 Daily requirements: 200-300µg.
 Pregnancy: 400µg.
Absorption –
• Upper small intestine.
Transport –
• Plasma protein bound 1/3.
• Considerable enterohepatic circulation
occurs
• Alcohol interferes with the release of
methyl-THFA by hepatocytes
• only traces are excreted; but in
pharmacological doses 50-90% are excreted.
 Epithelial surfaces: macrocytosis
 Infertility in both men and women
 CVD – IHD.
 Malignancy : Acute Lymphoblastic
Leukemia of childhood.
 Neurologic : bilateral peripheral
neuropathy and degeneration; Alzhiemer’s
disease
 Maternal: prematurity; abortion; neural
tube defects
 Children: poor brain development ;
impaired intellectual development.
Haematological findings
 Oval macrocytes
 Anisocytosis (varied sizes )
 Poikilocytosis ( abnormal shaped )
 Hypersegmanted neutrophils
 Howell – jolly bodies
 Unconjugated bilirubin
 Haptoglobins
 Urine – urobilinogen, hemosiderin.
 Howell jolly
bodies are the
basophilic
nuclear
remnants in
the circulating
erythrocytes
ELISA findings
 Serum cobalamin
normal:160-1000 ng/L
severe anemia <100ng/L
 Serum folate
normal: 2µg/L-15µg/L
 Red cell folate
normal: 160 - 640µg/L.
Treatment
Cobalamin:
 Hydroxocobalamin is preferred because it
is more highly protein-bound and
therefore remains longer in the
circulation.
 Initial therapy should consist of 100–1000
mcg of vitamin B12 intramuscularly daily
or every other day for 1–2 weeks to
replenish body stores.
 Maintenance therapy consists of 100–
1000 mcg intramuscularly once a month
for life.
 If neurologic abnormalities are present,
maintenance therapy injections should be
given every 1–2 weeks for 6 months
before switching to monthly injections.
 Oral doses of 1000 mcg of vitamin B12
daily are usually sufficient to treat patients
with pernicious anemia who refuse or
cannot tolerate the injections.
 After pernicious anemia is in remission
following parenteral vitamin B12 therapy,
the vitamin can be administered
intranasally as a spray or gel.
 Folate: 5-15mg; for 4 months
 Parenteral administration of folic acid is
rarely necessary, since oral folic acid is
well absorbed even in patients with
malabsorption syndromes.
 Therapy should be continued until the
underlying cause of the deficiency is
removed or corrected.
 Therapy may be required indefinitely for
patients with malabsorption or dietary
inadequacy.
 Folic acid supplementation to prevent
folic acid deficiency should be considered
in high-risk patients, including pregnant
women, patients with alcohol dependence,
hemolytic anemia, liver disease, or certain
skin diseases, and patients on renal
dialysis.
 Prophylactic folic acid foods – bread,
wheat, rice.
 Potasssium supplements if needed.
 Antiplatelets if needed.
Non megaloblastic but
macrocytic anemias
 RBC’s are round not oval
 There are no hypersegmented neutrophils
and howell – jolly bodies
Macrocytosis without megaloblastosis