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v    Causes:

1.     Megaloblastic anemia.

2.     Alcohol: when it causes liver diseases.

3.     Liver diseases.

4.     Reticulocytosis.

5.     Cytotoxic drugs: e.g. methotrexate.

6.     Aplastic anemia.

7.     Myelodysplastic syndromes.

8.     Neonatal.

Megaloblastic Anemia

Causes

o       Vit B₁₂ def.

o       Folate def.

o       Alcohol.

Vit B₁₂ (cobalamine)

v    Physiology:  

v    Deficiency:

Table 1.  Causes of Vit B₁₂ deficiency.  Note that deficiency inevitably takes at least 2 years to develop.

Malabsorption:

PA, total / partial gastrectomy.

Intestinal causes:

ü     Celiac disease.

ü     Terminal ileal resection.

ü     Crohn’s disease.

ü     Fish tapeworm.

o       Pernicious Anemia (PA):

§        Achlorhydria.

§        No IF.

§        Autoimmune & associated with other autoimmune diseases.

§        Associated with blood group A.

§        Anti-parietal cells Abs (I & II) & anti-IF Abs.

Folate

v    Physiology:

o       Not synthesized in humans.

à Require preformed vitamin.

o       Absorbed through duodenum & jejunum.

o       Folates are needed in:

§        Transfer of   C1 fragments.

§        DNA synthesis:

·        Purines, Thymine (a pyrimidine), Methionine synthesis.

Fig. 2.  The biochemical bases for megaloblastic anemia due to Vit B₁₂ / folate deficiency. 5, 10-methylene THF polyglutamate is folate coenzyme.

* THF = Tetrahydrofolate

v    Deficiency:

Table 2.  Causes of folate deficiency.

Malabsorption:

Tropical sprue, celiac diseases, Crohn’s disease.

Excess Utilization:

Physiological:  Pregnancy, lactation, prematurity.

Pathological: Hemolytic anemia, malignancies.

Clinical  Features

o       Mild jaundice.

o       Glossitis (beefy-red, sore tongue).

o       Angular stomatitis (cheilosis).

o       Weight loss.

·        N.B. Vit B₁₂ neuropathy (subacute combined degeneration of the cord):

o       Complications of Vit B₁₂ deficiency.

o       Cause (?).

o       Symmetrical, but affects > lower limb.

o       ♂

o       Demyelination of dorsal & dorsolateral columns.

Lab

1.    Blood film:

a.     Oval macrocytes.

b.    Hypersegmented PMNs.

c.     Basophilic stippling.

2.    CBC:  

Retics. WBCs. Platelets. Mature RBCs. Hb, Hct.
MCV

3.:

S-unconj Bilirubin.
LDH

4.     BM:   Hypercellular megaloblasts, giant metamyelocytes.

5.    Serum Vit B₁₂.

6.     Schilling test:

a.      Give labeled (oral) & non-labeled B₁₂ (i.m to restore liver stores).

b.     Collect urine for 24h.

Normal subjects excrete > 10% of radioactive B₁₂.

à Indirect measurement of B₁₂ absorption.

Differential   diagnosis   for Macrocytic  anemia  depends  on:

1.    History:

o       Family history.

o       Malabsorption.

o       Autoimmune diseases.

o       Previous GI diseases / operations.

2.    Physical exam:

o       Jaundice.

o       Glossitis.

o       Neuropathy

3.    Lab diagnosis.  

written by: Khalid Bin Yaroof. FMHS, UAE University.