MLAB 1415- Hematology

Keri Brophy-Martinez

Chapter 12: Macrocytic Anemias

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

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 resulting in maturation delays, prolonging the premitotic interval Results

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 Macrocytic, normochromic anemia

Increased MCH: due to large cell volume Normal MCHC

RBC, HGB, Hct decreased 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)

Megaloblastic Anemia: Causes of 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. Malabsorptiona. 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)

c. Gastrectomyd. Blind loop syndrome

bacteria use up the B12

d. Fish tapeworm= Diphyllobothrium latum completes for B12

Other Causes for B12 Deficiency

3. Drugsa. Alcoholb. Nitrous oxidec. Antitubercular drug

Megaloblastic Anemia:Folic Acid (Folate) deficiency

1. Inadequate dietary intakea. Povertyb. Old agec. Alcoholism

Megaloblastic Anemia:Folic Acid (Folate) deficiency2. Malabsorption

a. Ileitis/Crohn’s diseaseb. Tropical spruec. Blind loop syndromed. Nontropical sprue

a. Gluten-sensitive enteropathyb. Childhood celiac disease

Megaloblastic Anemia:Folic Acid (Folate) deficiency

3. Increased requirementa. 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. Infancyc. Hematologic diseases that involve rapid cellular

proliferation such as sickle cell anemia

Megaloblastic Anemia:Folic Acid (Folate) deficiency

4. Drugsa. Methotrexate (chemotherapy drug that is a

folate antagonist)b. Alcoholc. Oral contraceptivesd. 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

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 Causes of

Chronic liver disease Alcoholism (alcohol has toxic effect on

RBC’s) Stimulated Erythropoiesis

Anemia associated with liver diseaseCauses 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.