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

2. 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)

3. 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

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 as a result of impaired DNA synthesis
Megakaryoctyes are abnormal resulting in thrombocytopenia

6. 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

7. 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)

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

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

11. 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

12. 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

13. 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

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

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

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

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

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

19. 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

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

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

22. 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

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

24. 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

25. 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

26. 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.