Anemias megaloblastic
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Transcript of Anemias megaloblastic
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ANEMIAS OF ABNORMAL NUCLEAR DEVELOPMENT: Megaloblastic Anemia
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Etiology
Vitamin B12 deficiency/Pernicious anemia
Folate deficienc
Combined deficiencies
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Etiology: Pernicious Anemia
Gastric atrophy
Results in decreased secretion of intrinsic factor (IF) by parietal cells
Destruction of vitamin B12 in GI tract
Other causes
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Etiology: Folate Deficiency
Dietary deficiencyAlcoholic cirrhosisPregnancyInfant malnutritionFolate antagonists
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Pathophysiology
B12 and folate deficiencies result in
defective DNA synthesis
This results in an abnormal cell maturation processMost likely megaloblastic cells die in the bone marrow
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Major Clinical Characteristics
B12 deficiency: Neurologic symptoms,
glossitis (beefy red tongue); gastrointestinal symptoms
Folate deficiency: Similar to features above, but without neurological
problems
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Megaloblastic Anemia:Laboratory Testing
HemogramMorphologyBone marrow examination (rare)Serum B12
Serum folateOther tests
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Hemogram Pattern in Megaloblastic Anemia
WBC N/Hgb MCVPLT N/
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Peripheral Blood Morphology
AnisocytosisMacro-ovalocytesPossible megaloblastsGiant and hyperseg-
mented neutrophils (PA polys)Possible granule deficient platelets
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DARAH TEPI
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Macrocyte vs. Macrocyte
Macroovalocyte
RPI<2
PolychromatophilicMacrocyte
RPI>3
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Bone Marrow Findings
HypercellularPredominantly megaloblastic erythropoiesisGiant granulocyte precursorsNuclear-cytoplasmic asynchronyPossible decreased megakaryocytes
and nuclear changes
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BMP ANEMIA MEGALOBLASTIK
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Megaloblastic vs. Megaloblastoid
Megaloblastic Caused by B12 or
folate deficiency
All blood cell lines affected
Megaloblastoid Not caused by B12 or
folate deficiency; seen in myeloproliferative and myelodysplastic disorders
Selected cell lines affected; other nuclear anomalies may be present
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Serum B12 and Folate Assays
Principle: Competitive protein binding
radioimmunoassay
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Serum B12 and Folate Assays
B12
57Co
IF
F
L125I
IF
L
F
125IF
125I
B12
B12
57Co
57Co
B12 Pt’s Vitamin B12
F Pt’s Folate
57Co 57Co-labeled cobalamin
125I 125I-labeled folic acid
IF Intrinsic factor L -lactoglobulin
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Serum B12 and Folate Assays
Washing to remove unbound radioactive labels
-scintillation countingResidual radioactivity is inversely
proportional to the amount of patient’s B12 and folate
Result determined by comparison to standard curve
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Serum B12 and Folate Assays
Specimen requirements Serum preferred EDTA plasma acceptable Fasting specimen for folate Avoid hemolysis for folate assay
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Serum B12 and Folate Assays
Specimen storage Protect from light (folate) 2-8°C for 3 hours -20°C longer periods
Specimen preparation: boiled or exposed to an alkaline agent
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Serum B12 and Folate Assays
Reference ranges Serum B12: 100-700 pg/mL Serum Folate: 3-16 ng/mL
Lower limit for B12 deficiency not well defined
In untreated patients with folate deficiency levels are usually <1.0 ng/mL
Other tests may be needed in borderline cases
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Other Tests
Schilling testUrine formiminoglutamic acid (FIGlu):
Increased in B12 and folate deficiencyUrine/serum methylmalonic acid
(MMA) Specific for B12 deficiency
Elevated in B12 deficiency
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TreatmentIntramuscular injections of vitamin B12 every
1-3 monthsEffects
Increased retic count in 5-7 days HCT in reference range in 1-2 months Other RBC parameters return to normal Hypersegmented neutrophils disappear in 2
weeks
Platelet count normal within 7 days