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MEGALOBLASTIC ANEMIA
Clinical Competencies
Be able to describe:
- the etiology of megaloblastic anemia caused by
vitamin B12 and folate deficiency
- the pathophysiology of megaloblastic anemia
- the principal management of megaloblastic anemia
caused by vitamin B12 and folate deficiency
Be able to diagnose megaloblastic anemia based on
clinical features and laboratory findings
Faculty of Medicine
University of Brawijaya
Introduction
Megaloblastic anemia
A heterogeneous group of anemia characteristics:
- RBC are larger: nuclear-to-cytoplasmic ratio >
normoblast
- The maturation of nuclei is delayed, cytoplasmic
development is normal
Based on the appearance of developing erythroblasts in
the bone marrow: megaloblastic & non-megaloblastic
There are several causes, but megaloblastic anemia is
usually caused by vitamin B12 or folate deficiency.
Faculty of Medicine
University of Brawijaya
Etiology
In clinical practice, this is usually caused by vitamin B12
(cobalamine) or folate deficiency.
Causes of vitamin B12 deficiency
Nutritional
Malabsorption: gastric and intestinal causes
Causes of folate deficiency
Nutritional
Malabsorption
Excess urinary folate loss
Drugs
Excess utilization
Mixed
Faculty of Medicine
University of Brawijaya
Faculty of Medicine
University of Brawijaya
Faculty of Medicine
University of Brawijaya
Pathophysiology
The molecular basis: a failure in the synthesis and
assembly of DNA.
Cobalamin & folate metabolism are intricately related, and
abnormalities in these pathways are believed to lead
to the attenuated production of DNA.
Megaloblastosis is caused by interference of folate
metabolism by the inhibition of methionine synthesis.
Dietary folate deficiency the size of the deoxythymidine
triphosphate (dTTP) pool is normal or increased in
persons with megaloblastosis.
Faculty of Medicine
University of Brawijaya
Faculty of Medicine
University of Brawijaya
Faculty of Medicine
University of Brawijaya
Diagnosis
Based on clinical features and laboratory findings
Clinical Features
Mildly jaundice (lemon yellow tint)
Glossitis (a beefy-red, sore tongue)
Angular stomatitis
Mild symptoms of malabsorption with loss of weight
caused by epithelial abnormality
Purpura as a result of thrombocytopenia and widespread
melanin pigmentation
Faculty of Medicine
University of Brawijaya
Faculty of Medicine
University of Brawijaya
Laboratory Findings
Pancytopenia
Increased MCV and MCHC
Hypersegmented neutrophils (five lobes or more
in segmented neutrophils)
Increased bilirubin
Increased LDH
Hyperplasia in the bone marrow
Decreased M:E ratio
Reticulocytopenia
Faculty of Medicine
University of Brawijaya
Faculty of Medicine
University of Brawijaya
Folate Deficiency
Compound: folic acid
Route: oral
Dose: 5 mg
Initial dose: daily for 4 months
Maitenance: depends on underlying disease; life-long
therapy may be needed in chronic inherited hemolytic
anemia, myelofibrosis, renal dialysis
Prophylactic: pregnancy, severe hemolytic anemia,
dialysis, prematurity
Faculty of Medicine
University of Brawijaya