Hem & Onc - Pathology (Microcytic Anemia)

Question 1

What defines microcytic anemia? How does it appear on blood smear? What are examples of microcytic anemia?

Answer 1

MCV < 80 fL; Hypochromic; (1) Iron deficiency anemia (2) Thalassemias (3) Lead poisoning (4) Sideroblastic anemia (5) Anemia of chronic disease (if progresses to this from normocytic anemia)

Question 2

What are causes of iron deficiency?

Answer 2

(1) Chronic bleeding (e.g., GI loss, menorrhagia) (2) Malnutrition/absorption disorders (3) Increased demand (e.g., pregnancy)

Question 3

What metabolic effect does iron deficiency have?

Answer 3

Decrease final step in heme synthesis

Question 4

What are the lab findings (i.e., iron studies) of iron deficiency anemia?

Answer 4

(1) Decreased iron (2) Increased TIBC (3) Decreased ferritin

Question 5

What are the blood smear findings of iron deficiency anemia?

Answer 5

Microcytosis and hypochromia

Question 6

What condition might iron deficiency anemia manifest as? What characterizes this condition?

Answer 6

Plummer-Vinson syndrome; Triad of iron deficiency anemia, esophageal webs, & atrophic glossitis

Question 7

What is the defect in alpha-thalassemia? What is the result of this defect?

Answer 7

alpha-globin gene deletions; Decreased alpha-globin synthesis

Question 8

What is key to remember about 1 alpha-globin allele deletion in alpha-thalassemia?

Answer 8

No clinically significant anemia

Question 9

What is key to remember about 2 alpha-globin allele deletions in alpha-thalassemia?

Answer 9

No clinically significant anemia; However, deletions may be cis or trans (which have important epidemiological implications): Cis deletion prevalent in Asian populations & Trans deletion prevalent in African populations

Question 10

Cis and Trans deletions are relevant in the case of how many alpha-globin allele deletions? In what populations are cis versus trans deletions prevalent?

Answer 10

2; Cis = Asian, Trans = African

Question 11

What is key to remember about 3 alpha-globin allele deletions in alpha-thalassemia? More specifically, how much alpha-globin is present and what Hb disease forms?

Answer 11

HbH disease. Very little alpha-globin. Excess Beta-globin forms Beta4 (HbH)

Question 12

What is key to remember about 4 alpha-globin allele deletions in alpha-thalassemia? More specifically, how much alpha-globin is present and what Hb disease forms?

Answer 12

No alpha-globin. Excess gamma-globin forms gamma4 (Hb Barts). Incompatible with life (causes hydrops fetalis)

Question 13

What is the disease that results from 4 alpha-globin allele deletions in alpha-thalassemia? What does this mean for the affected patient?

Answer 13

Hydrops fetalis (due to no alpha-globin & gamma4 Hb Barts); Incompatible with life

Question 14

What causes Beta-thalassemia, and what is the result?

Answer 14

Point mutations in splice sites and promoter sequences; Decreased Beta-globin synthesis

Question 15

In what populations is Beta-thalassemia prevalent?

Answer 15

Mediterranean

Question 16

What is one word to describe the genetic makeup of a Beta-thalassemia minor patient? What happens to their Beta chain?

Answer 16

Heterozygote; Beta chain is underproduced

Question 17

What are the symptoms of Beta-thalassemia minor? What confirms diagnosis?

Answer 17

Usually asymptomatic; Diagnosis confirmed with increased HbA2 (> 3.5%) on electrophoresis

Question 18

What is one word to describe the genetic makeup of a Beta-thalassemia major patient? What happens to their Beta chain?

Answer 18

Homozygote; Beta chain is absent

Question 19

What are major signs/symptoms of Beta-thalassemia major?

Answer 19

(1) Severe anemia (due to absent Beta chain) (2) Marrow expansion (“crew cut” on skull x-ray) –> skeletal deformities (e.g., chipmunk faces)

Question 20

What secondary condition is associated with Beta-thalassemia major, and why?

Answer 20

Secondary hemochromatosis; Severe anemia requires blood transfusion

Question 21

What can be seen on electrophoresis in Beta-thalassemia major? What can be seen on blood smear?

Answer 21

Increased HbF (alpha2, gamma2); Microcytosis, hypochromia, anisocytosis, poikilocytosis, target cells, & schistocytes

Question 22

What degree of sickle cell disease is seen in HbS/Beta-thalassemia heterozygotes? On what does this depend?

Answer 22

Mild to moderate; Amount of Beta-globin production

Question 23

What effect does lead have on heme synthesis, and how?

Answer 23

Decrease; Lead inhibits ferrochetelase and ALA dehydratase

Question 24

What is the classic blood smear finding in lead poisoning, and why?

Answer 24

Basophilic stippling; Lead inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA

Question 25

What is a high risk to keep in mind for lead poisoning?

Answer 25

Houses with chipped paint

Question 26

What are the clinical findings in lead poisoning? What is the first line treatment for lead poisoning? What is a good mnemonic to remember these things?

Answer 26

(1) Lead Lines on gingivae (burton's lines) & on metaphyses of long bones on x-ray (2) Encepalopathy (3) Erythocyte basophilic stippling (4) Abdominal colic (5) sideroblastic Anemia (6) Drops - foot and wrist drops; Dimercaprol and eDta; LEAD (which is really more like LLEEAADDD)

Question 27

What is used for chelation for kids in cases of lead poisoning?

Answer 27

Succimer

Question 28

What is the defect in sideroblastic anemia? More specifically, what is the mutation and mode of inheritance?

Answer 28

Heme synthesis (due to protoporphyrin deficiency); X-linked defect in deta-ALA synthase gene

Question 29

What are the general types of causes of sideroblastic anemia?

Answer 29

(1) Genetic (2) Acquired (myelodysplastic syndrome) (3) Reversible (alcohol is most common, lead, vitamin B6 deficiency, copper deficiency, isoniazid)

Question 30

What causes the appearance of ringed sideroblasts?

Answer 30

Iron-laden mitochondria (due to protoporhyrin deficiency)

Question 31

What are the lab findings (i.e., iron studies) in sideroblastic anemia?

Answer 31

(1) Increased iron (2) Normal TIBC (3) Increased ferritin

Question 32

How is sideroblastic anemia treated, and why?

Answer 32

Pyridoxine (B6, cofactor for delta-ALA synthase, which is what is affected in sideroblastic anemia)

Question 33

Name a physical exam finding commonly indicative of anemia.

Answer 33

Conjunctival pallor

Question 34

What kind of condition serves as an acquired cause of sideroblastic anemia?

Answer 34

Acquired (myelodysplastic syndromes)

Question 35

What are 5 reversible causes of sideroblastic anemia? Which is most common?

Answer 35

Reversible (alcohol is most common, lead, vitamin B6 deficiency, copper deficiency, and isoniazid)