MLAB 1415- Hematology Keri Brophy-Martinez Macrocytic Anemias.

MLAB 1415- Hematology

Keri Brophy-Martinez

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 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.