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MLAB 1415- Hematology Keri Brophy-Martinez
Macrocytic Anemias
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Macrocytic Anemia Megaloblastic Nonmegaloblastic
Abnormal DNA synthesis, usually due to vitamin B12 or folate deficiencies Results in delayed nuclear development, causing the larger cells Nonmegaloblastic Mechanism not well defined Increase in membrane lipids DNA synthesis unimpaired Characterized by large erythrocytes( MCV> 100)
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Megaloblastic Anemias
“Megaloblast”: large abnormal marrow erythocyte precursor Group of disorders characterized by defective nuclear maturation caused by impaired DNA synthesis. Impairment is a result of a substitution in the nucleic acid chain, causing DNA replication to be fragmented. Nuclear replication is slowed down or stopped resulting in maturation delays, prolonging the premitotic interval Cellular observation Large nucleus Cytoplasm development normal Hgb synthesis normal- because RNA strands are not affected
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Megaloblastic Anemias: Clinical Findings
Anemia is slow to develop Fatigue Weakness Yellow color Weight loss Glossitis
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Megaloblastic Anemia: Lab Features: Hematology
Macrocytic, normochromic anemia Increased MCH: due to large cell volume Normal MCHC RBC, HGB, Hct decreased to normal Reticulocytopenia Granulocytes and Thrombocytes are affected as well. Granulocytes are hypersegmented as a result of impaired DNA synthesis Megakaryoctyes are abnormal resulting in thrombocytopenia
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Megaloblastic Anemia: Lab Features: Peripheral blood
Triad of: oval macrocytes Howell-Jolly bodies-DNA fragments hypersegmented neutrophils Anisocytosis, Poikilocytosis RBC’s are fragile, lifespan is shortened and many die in the bone marrow which causes ↑ LDH
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Megaloblastic Anemia: Lab Features: Misc
Bone marrow Chemistries Hypercellular with megaloblastic erythroid precursors M:E ratio decreased Vitamin B12 Folate Iron Panel Methylmalonic acid (MMA) Homocysteine Lactic dehydrogenase(LDH)
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Causes of Megaloblastic Anemia
Vitamin B 12 deficiency Folate deficiency Drugs Myelodysplastic syndromes Acute leukemia
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Causes of Vitamin B12 Deficiency- SUMMARY
Inadequate dietary intake Malabsorption Pernicious anemia Gastrectomy Blind loop syndrome Fish tapeworm Helicobacter pylori Drugs Increased need
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Megaloblastic Anemias: Deficiency of Vitamin B12
Vitamin B12 (cyanocobalamin) deficiency Inadequate dietary intake B12 is found in food of animal origin: red meat, fish, poultry, eggs, dairy products
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Megaloblastic Anemias: Deficiency of Vitamin B12
Malabsorption Pernicious anemia Caused by gastric parietal cell atrophy which causes decreased secretion of intrinsic factor (IF). IF is necessary for B12 absorption. Atrophy due to immune destruction of the acid-secreting portion of the gastric mucosa Onset is usually after age 40, primarily women Affects people of Northern European backgrounds Neurologic problems Schilling test used for diagnosis
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Schilling test Establishes the cause of vitamin B12 deficiency
Test performed in two parts If parts one & two abnormal: Pernicious anemia If part one only abnormal: malabsorption
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B12 Malabsorption causes (con’t)
Gastrectomy Blind loop syndrome bacteria use up the B12 Fish tapeworm= Diphyllobothrium latum completes for B12 Helicobacter pylori infections
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Other Causes for B12 Deficiency
Drugs Alcohol Nitrous oxide Antitubercular drugs Increased Need Pregnancy/lactation Growth
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Causes of Folic Acid Deficiency- SUMMARY
Inadequate Dietary Update Malabsorption Increased Need Drugs
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Megaloblastic Anemia: Folic Acid (Folate) Deficiency
Inadequate dietary intake Poverty Old age Alcoholism
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Megaloblastic Anemia: Folic Acid (Folate) Deficiency
Malabsorption Ileitis/Crohn’s disease Tropical sprue Blind loop syndrome Nontropical sprue Gluten-sensitive enteropathy Childhood celiac disease
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Megaloblastic Anemia: Folic Acid (Folate) Deficiency
Increased need Pregnancy There is increased demand during pregnancy and should be supplemented prior to and during pregnancy. Deficiency during pregnancy can cause neural tube defects in utero. Infancy Hematologic diseases that involve rapid cellular proliferation such as sickle cell anemia
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Megaloblastic Anemia: Folic Acid (Folate) Deficiency
Drugs Methotrexate (chemotherapy drug that is a folate antagonist) Alcohol Oral contraceptives Long term anticoagulant drugs
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Treatment of megaloblastic anemia
B12 deficiency Vitamin therapy Intramuscular or subcutaneous injections for pernicious anemia to bypass absorption through the gut. Folate deficiency
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Non-Megaloblastic Anemia
DNA synthesis not impaired MCV doesn’t go as high as in megaloblastic Macrocytes are round NOT oval No hypersegmented neutrophils Leukocytes and platelets are normal Jaundice, glossitis and neuropathy are absent
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Causes of Non-Megaloblastic Anemia
Chronic liver disease Alcoholism alcohol has toxic effect on RBC’s Stimulated Erythropoiesis Newborns
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Anemia associated with liver disease
Causes of: Blood Picture: Blood loss Alcoholism Folate Deficiency Impaired bone marrow response Hemolysis Target cells Acanthocytes Macrocytes Hypochromia Microcytosis
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Anemia associated with:
Alcoholism: Ethanol has a toxic effect on precursor cells Red cells are macrocytic Stimulated erythropoiesis: Increased EPO, adequate iron Release of stress reticulocytes
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References Harmening, D. M. (2009). Clinical Hematology and Fundamentals of Hemostasis. Philadelphia: F.A Davis. McKenzie, S. B., & Williams, J. L. (2010). Clinical Laboratory Hematology . Upper Saddle River: Pearson Education, Inc. Turgeon, M. (2005). Clinical Hematology: Theory and Procedures. Baltimore: Lippincott Williams and Wilkins.
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