Hematology #1 (Microcytic Anemias)

Question 1

MCC of anemia worldwide

Answer 1

Iron Deficiency Anemia

Question 2

Etiologies of iron deficiency

-In US
-In World

Answer 2

US: Chronic blood loss (menstruation, colon cancer, parasitic hookworms)

World: Diet (Celiac, H. Pylori, Bariatric surgery)

Question 3

What are some risk factors for iron deficiency anemia? (Think of states that have increased metabolic requirements)

Answer 3

-Children, pregnant, lactating women
-Cow milk ingestion younger than 1 year of age

Question 4

What is the pathophysiology of iron deficiency anemia?

Answer 4

Decreased production of RBC’s due to lack of iron and decreased iron stores (ferritin)

Question 5

Symptoms of iron deficiency anemia

Answer 5

-Fatigue, weakness, dyspnea
-Pasophagia (ice craving)
-Pica (crave clay, starch)
-Koilonychia (spooning of nails)
-Angular cheilitis
-Glossitis (smooth tongue)
-Leg cramps climbing stairs

Question 6

What is shown on a CBC for iron deficiency anemia?

Iron studies show…

Answer 6

CBC: microcytic hypochromic anemia
–reduced iron stores halt production of hemoglobin = hypo chromic (not red)
–Reduced RDW (red cell distribution width) = mix of small and large cells

Iron Studies: decreased ferritin (iron stores), increased TIBC (transferrin = delivers iron, decreased transferrin saturation (serum iron/iron binding capacity), decreased serum iron

Question 7

However, what is the definitive diagnostic for iron deficiency anemia?

Answer 7

Bone marrow biopsy: absent iron stores

Question 8

Treatment for iron deficiency anemia

Answer 8

-iron replacement (corrects anemia in 6-8 months)
–Ex: Ferrous sulfate 325 mg PO daily

-If severe, red blood cell transfusion

Question 9

Recommendations for taking iron supplements

Answer 9

-Take iron supplement with Vitamin C (ascorbic acid), with water or juice, on an empty stomach
-Take 2 hours before or 4 hours after antacids

Question 10

What is a normal MCV?

What is the MCV in iron deficiency anemia?

Answer 10

Normal: 80-100

Iron Deficiency: Microcytic <80

Question 11

Explain the pathophysiology of lead poisoning anemia (plumbism)

Answer 11

-Lead poisons enzymes, causing cell death, shortens the lifespan of RBC’s, and inhibits enzymes needed for heme synthesis –> acquired sideroblastic anemia

Question 12

Risk Factors for lead poisoning anemia

-Who is it MC in?
-What is the MCC?

Answer 12

-MC in children due to increased permeability of blood-brain barrier and iron deficiency (increases lead absorption)
-MCC is ingestion or inhalation of environmental lead (paint chips or lead dust)

Question 13

Symptoms of lead poisoning anemia

Answer 13

-Neuro symptoms: ataxia, fatigue, learning disabilities, difficulty concentrating, hearing loss, developmental delays
-Peripheral neuropathy: wrist or foot drop
-Intermittent abdominal pain, loss of appetite, constipation
-Burton’s Line: thin, blue black line at base of gums near the teeth

Question 14

What is the initial diagnostic done for lead poisoning anemia?

Answer 14

Capillary fingerstick sample: Serum lead level > 10 mcg/dL

Question 15

What is seen on peripheral smear for lead poisoning anemia?

Answer 15

Microcytic hypo chromic anemia with basophilic stippling (dots of denatured RNA in RBC’s)

Question 16

However, what is seen on bone marrow biopsy for lead poisoning anemia?

Answer 16

Ringed sideroblasts

–immature RBC surrounded by rings of iron. Storing iron instead of using it.

Question 17

What is a unique finding on radiographs in lead poisoning?

Answer 17

Lead lines: linear hyper densities at the metaphyseal plates in children

Question 18

Treatment for lead poisoning anemia
-First option:
-Mild 44 mcg/dL or lower:
-Moderate (45-69):
-Severe (70 or higher):

Answer 18

Removal of source of lead is most important component of treatment

Mild: outpatient follow up and lifestyle modifications

Moderate: Succimer (combines with lead in the bloodstream and is removed by kidneys)

Severe: Succimer + Calcium disodium edetate

Question 19

What exactly is thalassemia?

What are some risk factors?

Answer 19

Decreased production of globin chains

Runs in families, SE Asians, Mediterraneans

Question 20

When should you suspect a thalassemia (what is shown on labs that would lead you to this?)

Answer 20

-Microcytic anemia with normal/increased Iron or no response to Iron treatment

Question 21

Explain what happens in beta thalassemia

What is one RF that you should remember with this condition?

Answer 21

Decreased production of beta-globin chains leading to excess alpha chains

Mediterranean (Greek, Italians)

Question 22

How many alpha and beta globin chains are in a normal adult HgbA cell?

Answer 22

2 alphas and 2 betas

Question 23

Explain beta thalassemia minor vs major (Cooley’s Anemia

Answer 23

-Minor: only one gene is defective. MC type! Usually asymptomatic

Major (Cooley’s Anemia): both beta genes mutated. Ineffective erythropoeisis and shortened RBC lifespan

Question 24

When do symptoms occur in beta thalassemia major and why?

What are some of the symptoms?

Answer 24

-After 6 months of life, when fetal hemoglobin begins to diminish

-Pallor, irritability, dyspnea, mental delays
-Hemolytic anemia: jaundice, splenomegaly
-Osteoporosis by age 10, compression fractures, disc degeneration (red marrow replaced by inactive yellow)
-Hypogonadism, DM, growth failure
-Cardiac dysfunction: heart failure
-Enlarged kidneys
-Bony abnormalities, hair on end appearance of skull

Question 25

Explain what is seen on hemoglobin electrophoresis in beta-thalassemia in both types.

Answer 25

-Minor: decreased HgbA, increased Hgb F -Major: Little to no HgbA, very high Hgb F

Question 26

What is one advantage of Hgb F in comparison to the other types?

Answer 26

It has a stronger affinity for oxygen, so those with thalassemia have higher amounts of it to make up for the lack of HgbA

Question 27

What is seen on CBC and peripheral smear with beta-thalassemia major (think size, shape, etc.)

Answer 27

-Microcytic hypo chromic anemia -Normal or increased serum Fe Peripheral smear: target cells , teardrop cells, basophilic stippling

Question 28

Explain the significance of target cells

Answer 28

-Centrally located disc of hemoglobin surrounded by abundance of cell membrane (due to lack of globin chains)

Question 29

What is seen on skull radiographs in beta-thalassemia?

Answer 29

Hair on end appearance: due to extramedually hematopoeisis

Question 30

What is the treatment for beta thalassemia major?

Answer 30

-Frequent transfusions -Iron chelating agents (Deferoxamine) to remove excess iron from chronic transfusions. -Vitamin C and folate supplementation (substrates for RBC production) -Splenectomy in some cases (stops RBC destruction)

Question 31

Explain the pathophysiology of Alpha Thalassemia

Answer 31

-3/4 gene deletions cause decreased alpha chain production and excess beta chains. The beta chains form insoluble beta chain tetramers (Heinz bodies) with no oxygen carrying capacity in the RBC's. They are then destroyed by the spleen (hemolytic anemia).

Question 32

Symptoms of alpha thalassemia

Answer 32

-Symptomatic at birth (unlike beta thalassemia) -Anemia, jaundice -Hepatosplenomegaly -Gallstones -Increased bone marrow hematopoesis: frontal bossing, maxilla overgrowth

Question 33

Hemoglobin H Disease (Alpha Thalassemia Intermedia) is characterized by ______ gene deletions and the presence of _______.

Answer 33

3/4 gene deletions Heinz Bodies (HbH - beta chain tetramer)

Question 34

On the other hand, Hydrops Fetalis is characterized by _______ gene deletions and the presence of _________. This is associated with stillbirth or death shortly after birth.

Answer 34

4/4 gene deletions HgB Barts: gamma tetramers

Question 35

What is seen on CBC and peripheral smear in alpha thalassemia (Hemoglobin H Disease)?

Answer 35

-Microcytic Hemolytic Anemia (schistocytes, tear drop cells, increased reticulocytes --immature RBC's). Target cells, increased RBC count -Heinz Bodies -Normal or increased serum iron -Hemoglobin electrophoresis: HbH (beta chain tetramer)

Question 36

Treatment for alpha thalassemia (same as beta)

Answer 36

-Frequent blood transfusions -Iron chelating agents (Deferoxamine) to remove excess iron -Splenectomy in some cases (stops RBC destruction) -Bone marrow transplantation definitive in MAJOR

Question 37

What is one way to differentiate Alpha from Beta Thalassemia with labs?

Answer 37

Alpha will have normal Hb ratios in adults, whereas Beta will be decreased.

Question 38

What is one thing to avoid as treatment in patients with thalassemia?

Answer 38

Avoid iron supplementation: they are already in iron overload