MLAB 1415- Hematology Keri Brophy-Martinez Macrocytic Anemias

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)

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

Megaloblastic Anemias: Clinical Findings Anemia is slow to develop Fatigue Weakness Yellow color Weight loss Glossitis

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

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

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)

Causes of Megaloblastic Anemia Vitamin B 12 deficiency Folate deficiency Drugs Myelodysplastic syndromes Acute leukemia

Causes of Vitamin B12 Deficiency- SUMMARY Inadequate dietary intake Malabsorption Pernicious anemia Gastrectomy Blind loop syndrome Fish tapeworm Helicobacter pylori Drugs Increased need

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

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

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

B12 Malabsorption causes (con’t) Gastrectomy Blind loop syndrome bacteria use up the B12 Fish tapeworm= Diphyllobothrium latum completes for B12 Helicobacter pylori infections

Other Causes for B12 Deficiency Drugs Alcohol Nitrous oxide Antitubercular drugs Increased Need Pregnancy/lactation Growth

Causes of Folic Acid Deficiency- SUMMARY Inadequate Dietary Update Malabsorption Increased Need Drugs

Megaloblastic Anemia: Folic Acid (Folate) Deficiency Inadequate dietary intake Poverty Old age Alcoholism

Megaloblastic Anemia: Folic Acid (Folate) Deficiency Malabsorption Ileitis/Crohn’s disease Tropical sprue Blind loop syndrome Nontropical sprue Gluten-sensitive enteropathy Childhood celiac disease

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

Megaloblastic Anemia: Folic Acid (Folate) Deficiency Drugs Methotrexate (chemotherapy drug that is a folate antagonist) Alcohol Oral contraceptives Long term anticoagulant drugs

Treatment of megaloblastic anemia B12 deficiency Vitamin therapy Intramuscular or subcutaneous injections for pernicious anemia to bypass absorption through the gut. Folate deficiency

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

Causes of Non-Megaloblastic Anemia Chronic liver disease Alcoholism alcohol has toxic effect on RBC’s Stimulated Erythropoiesis Newborns

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

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

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. http://health.allrefer.com/health/vitamin-b12-vitamin-b12-source.html http://tiny.cc/hj7iy Turgeon, M. (2005). Clinical Hematology: Theory and Procedures. Baltimore: Lippincott Williams and Wilkins.