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Macrocytic Anemia
Megaloblastic 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.
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
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 Megakaryoctyes are abnormal resulting in
thrombocytopenia
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
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)
Causes of Megaloblastic Anemia
Vitamin B 12 deficiency Folate deficiency Drugs Myelodysplastic syndromes Acute leukemia
Megaloblastic Anemias: Deficiency of Vitamin B12
Vitamin B12 (cyanocobalamin) deficiency
1. Inadequate dietary intake
a. B12 is found in food of animal origin: red meat, fish, poultry, eggs, dairy products
Megaloblastic Anemias: Deficiency of Vitamin B12
2. Malabsorption
a. 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)
b. Gastrectomy
c. Blind loop syndrome bacteria use up the B12
d. Fish tapeworm= Diphyllobothrium latum completes for B12
e. Helicobacter pylori infections
Other Causes for B12 Deficiency
3. Drugsa. Alcohol
b. Nitrous oxide
c. Antitubercular drug
4. Increased Needa. Pregnancy/lactation
b. Growth
Megaloblastic Anemia:Folic Acid (Folate) deficiency
1. Inadequate dietary intake
a. Poverty
b. Old age
c. Alcoholism
Megaloblastic Anemia:Folic Acid (Folate) deficiency
2. Malabsorption
a. Ileitis/Crohn’s disease
b. Tropical sprue
c. Blind loop syndrome
d. Nontropical spruea. Gluten-sensitive enteropathy
b. Childhood celiac disease
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
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
Treatment of megaloblastic anemia
B12 deficiencyVitamin therapyIntramuscular or subcutaneous
injections for pernicious anemia to bypass absorption throught the gut.
Folate deficiencyVitamin therapy
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 loss Alcoholism Folate Deficiency Impaired bone marrow
response Hemolysis
Blood Picture: 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.