Anemias megaloblastic

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ANEMIAS OF ABNORMAL NUCLEAR DEVELOPMENT: Megaloblastic Anemia

EtiologyVitamin B12 deficiency/Pernicious anemia Folate deficienc Combined deficiencies

Etiology: Pernicious AnemiaGastric atrophy Results in decreased secretion of intrinsic factor (IF) by parietal cells Destruction of vitamin B12 in GI tract Other causes

Etiology: Folate DeficiencyDietary deficiency Alcoholic cirrhosis Pregnancy Infant malnutrition Folate antagonists

PathophysiologyB12 and folate deficiencies result in defective DNA synthesis This results in an abnormal cell maturation process Most likely megaloblastic cells die in the bone marrow

Major Clinical CharacteristicsB12 deficiency: Neurologic symptoms, glossitis (beefy red tongue); gastrointestinal symptoms Folate deficiency: Similar to features above, but without neurological problems

Megaloblastic Anemia: Laboratory TestingHemogram Morphology Bone marrow examination (rare) Serum B12 Serum folate Other tests

Hemogram Pattern in Megaloblastic AnemiaWBC Hgb MCV PLT N/qq q oo N/q

Peripheral Blood MorphologyAnisocytosis Macro-ovalocytes Possible megaloblasts Giant and hypersegmented neutrophils (PA polys) Possible granule deficient platelets

DARAH TEPI

Macrocyte vs. MacrocytePolychromatophilic Macrocyte

Macroovalocyte

RPI3

Bone Marrow FindingsHypercellular Predominantly megaloblastic erythropoiesis Giant granulocyte precursors Nuclear-cytoplasmic asynchrony Possible decreased megakaryocytes and nuclear changes

BMP ANEMIA MEGALOBLASTIK

Megaloblastic vs. MegaloblastoidMegaloblasticCaused by B12 or folate deficiency All blood cell lines affected

MegaloblastoidNot 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 AssaysPrinciple: Competitive protein binding radioimmunoassay

Serum B12 and Folate AssaysB12 B1257Co 57Co

F F125I 125I 125I

F

B12

57Co

B12 F

Pts Vitamin B12 Pts Folate Intrinsic factor

57Co 125I

57Co-labeled 125I-labeled

cobalamin

folic acid

F-lactoglobulin

Serum B12 and Folate AssaysWashing to remove unbound radioactive labels K-scintillation counting Residual radioactivity is inversely proportional to the amount of patient s B12 and folate Result determined by comparison to standard curve

Serum B12 and Folate AssaysSpecimen requirementsSerum preferred EDTA plasma acceptable Fasting specimen for folate Avoid hemolysis for folate assay

Serum B12 and Folate AssaysSpecimen storageProtect from light (folate) 2-8C for 3 hours -20C longer periods

Specimen preparation: boiled or exposed to an alkaline agent

Serum B12 and Folate AssaysReference rangesSerum 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