basic info about megaloblastic anaemia and its treatment.

1. MEGALOBLASTIC
ANEMIA

2. 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

4. 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.


5. 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

7. Absorption
Active
Passive
1%
• Intrinsic
factor
• buccal
• duodenal
• ileal

8. Absorption

9. 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.

10. 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.


11. 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

13. 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.


16. 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.

22. 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.


24. Haematological findings
Oval macrocytes
 Anisocytosis (varied sizes )
 Poikilocytosis ( abnormal shaped )
 Hypersegmanted neutrophils
 Howell – jolly bodies
 Unconjugated bilirubin
 Haptoglobins
 Urine – urobilinogen, hemosiderin.


26. Howell jolly
bodies are the
basophilic
nuclear
remnants in
the circulating
erythrocytes

28. 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.


29. Treatment

30. 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.

31. 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.


32. 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.


33. 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.


34. Non megaloblastic but
macrocytic anemias
RBC’s are round not oval
 There are no hypersegmented neutrophils
and howell – jolly bodies


35. Macrocytosis without megaloblastosis