1. MLAB 1415- Hematology Keri Brophy-Martinez Macrocytic Anemias

2. Macrocytic Anemia Megaloblastic Abnormal DNA synthesis, usually due to vitamin B 12 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)

3. Megaloblastic Anemias “Megaloblast”: large abnormal marrow erythocyte precursor Group of disorders characterized by defective nuclear maturation caused by impaired DNA synthesis. 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

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

5. 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 Megakaryoctyes are abnormal resulting in thrombocytopenia

6. Megaloblastic Anemia: Lab Features: Peripheral blood Triad of oval macrocytes, Howell-Jolly bodies and hypersegmented neutrophils Anisocytosis, Poikilocytosis RBC’s are fragile, lifespan is shortened and many die in the bone marrow which causes ↑ LDH

7. Megaloblastic Anemia: Lab Features: Misc Bone marrow Hypercellular with megaloblastic erythroid precursors M:E ratio decreased Chemistries Vitamin B12 Folate Methylmalonic acid (MMA) Homocysteine Lactic dehydrogenase(LDH)

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

10. Megaloblastic Anemias: Deficiency of Vitamin B 12 Vitamin B 12 (cyanocobalamin) deficiency 1. Inadequate dietary intake a. B 12 is found in food of animal origin: red meat, fish, poultry, eggs, dairy products

11. Megaloblastic Anemias: Deficiency of Vitamin B 12 2. Malabsorption a. Pernicious anemia  Caused by gastric parietal cell atrophy which causes decreased secretion of intrinsic factor (IF). IF is necessary for B 12 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

12. Schilling test Establishes the cause of vitamin B 12 deficiency Test performed in two parts If parts one & two abnormal: Pernicious anemia If part one only abnormal: malabsorption

13. B 12 Malabsorption causes (con’t) b. Gastrectomy c. Blind loop syndrome bacteria use up the B 12 d. Fish tapeworm= Diphyllobothrium latum completes for B 12 e. Helicobacter pylori infections

14. Other Causes for B 12 Deficiency 3. Drugs a. Alcohol b. Nitrous oxide c. Antitubercular drug 4. Increased Need a. Pregnancy/lactation b. Growth

15. Megaloblastic Anemia: Folic Acid (Folate) deficiency 1. Inadequate dietary intake a. Poverty b. Old age c. Alcoholism

16. Megaloblastic Anemia: Folic Acid (Folate) deficiency 2. Malabsorption a. Ileitis/Crohn’s disease b. Tropical sprue c. Blind loop syndrome d. Nontropical sprue a. Gluten-sensitive enteropathy b. Childhood celiac disease

17. Megaloblastic Anemia: Folic Acid (Folate) deficiency 3. Increased requirement a. Pregnancy i. 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. b. Infancy c. Hematologic diseases that involve rapid cellular proliferation such as sickle cell anemia

18. Megaloblastic Anemia: Folic Acid (Folate) deficiency 4. Drugs a. Methotrexate (chemotherapy drug that is a folate antagonist) b. Alcohol c. Oral contraceptives d. Long term anticoagulant drugs

19. Treatment of megaloblastic anemia B 12 deficiency Vitamin therapy Intramuscular or subcutaneous injections for pernicious anemia to bypass absorption throught the gut. Folate deficiency Vitamin therapy

20. 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

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

22. Anemia associated with liver disease Causes of: Blood loss Alcoholism Folate Deficiency Impaired bone marrow response Hemolysis Blood Picture: Target cells Acanthocytes Macrocytes Hypochromia Microcytosis

23. 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

24. 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://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.