Upload
sukhrian-muhda
View
166
Download
3
Tags:
Embed Size (px)
Citation preview
ANEMIAS OF ABNORMAL NUCLEAR DEVELOPMENT: Megaloblastic Anemia
Etiology
Vitamin B12 deficiency/Pernicious anemia
Folate deficienc
Combined deficiencies
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
Etiology: Folate Deficiency
Dietary deficiencyAlcoholic cirrhosisPregnancyInfant malnutritionFolate antagonists
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
Major Clinical Characteristics
B12 deficiency: Neurologic symptoms,
glossitis (beefy red tongue); gastrointestinal symptoms
Folate deficiency: Similar to features above, but without neurological
problems
Megaloblastic Anemia:Laboratory Testing
HemogramMorphologyBone marrow examination (rare)Serum B12
Serum folateOther tests
Hemogram Pattern in Megaloblastic Anemia
WBC N/Hgb MCVPLT N/
Peripheral Blood Morphology
AnisocytosisMacro-ovalocytesPossible megaloblastsGiant and hyperseg-
mented neutrophils (PA polys)Possible granule deficient platelets
DARAH TEPI
Macrocyte vs. Macrocyte
Macroovalocyte
RPI<2
PolychromatophilicMacrocyte
RPI>3
Bone Marrow Findings
HypercellularPredominantly megaloblastic erythropoiesisGiant granulocyte precursorsNuclear-cytoplasmic asynchronyPossible decreased megakaryocytes
and nuclear changes
BMP ANEMIA MEGALOBLASTIK
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
Serum B12 and Folate Assays
Principle: Competitive protein binding
radioimmunoassay
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
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
Serum B12 and Folate Assays
Specimen requirements Serum preferred EDTA plasma acceptable Fasting specimen for folate Avoid hemolysis for folate assay
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
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
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
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