Transcript MLAB 1315- Hematology Fall 2007 Keri Brophy

MLAB 1415- Hematology
Keri Brophy-Martinez
Chapter 12: Macrocytic Anemias
Macrocytic Anemia
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Megaloblastic
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Nonmegaloblastic
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Abnormal DNA synthesis, usually due to vitamin B12 or folate
deficiencies
Results in delayed nuclear development, causing the larger cells
Mechanism not well defined
Increase in membrane lipids
Characterized by large erythrocytes( MCV> 100)
Megaloblastic Anemias
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“Megaloblast”: large abnormal marrow erythocyte precursor
Group of disorders characterized by defective nuclear maturation
caused by impaired DNA synthesis.
Nuclear replication is slowed down resulting in maturation delays,
prolonging the premitotic interval
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Results
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Large nucleus
Increased cytoplasmic RNA
Early hgb synthesis
Megaloblastic Anemias:
Clinical Findings
•Anemia
is slow to
develop
•Fatigue
• Weakness
• Yellow color
•Weight loss
•Glossitis
Megaloblastic Anemia:
Lab Features: Hematology
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Macrocytic, normochromic anemia
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Increased MCH: due to large cell volume
Normal MCHC
RBC, HGB, Hct decreased
Granulocytes and Thrombocytes are
affected as well.
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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
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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)
Megaloblastic Anemia: Causes
of
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Vitamin B 12 deficiency
Folate deficiency
Drugs
Myelodysplastic syndromes
Acute leukemia
Megaloblastic Anemias:
Deficiency of Vitamin B12
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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
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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
c.
d.

bacteria use up the B12
Fish tapeworm= Diphyllobothrium latum
d.

completes for B12
Other Causes for B12 Deficiency
3.
Drugs
a.
b.
c.
Alcohol
Nitrous oxide
Antitubercular drug
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 sprue
a.
b.
Gluten-sensitive enteropathy
Childhood celiac disease
Megaloblastic Anemia:
Folic Acid (Folate) deficiency
3.
Increased requirement
a. Pregnancy
a. 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 deficiency
 Vitamin therapy
 Intramuscular or subcutaneous
injections for pernicious anemia to
bypass absorption throught the gut.

Folate deficiency
 Vitamin therapy
Non-Megaloblastic Anemia
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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
Non-Megaloblastic Anemia
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Causes of
 Chronic liver disease
 Alcoholism (alcohol has toxic effect on
RBC’s)
 Stimulated Erythropoiesis
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:
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Alcoholism:
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Ethanol has a toxic effect on precursor cells.
Red cells are macrocytic
Stimulated erythropoiesis:
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Increased EPO, adequate iron
Release of stress reticulocytes
References
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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-vitaminb12-source.html
http://tiny.cc/hj7iy
Turgeon, M. (2005). Clinical Hematology: Theory
and Procedures. Baltimore: Lippincott Williams and
Wilkins.