Disorders of Hemoglobin

Question 1

What is hemoglobin’s isoelectric point?

Answer 1

6.8

Question 2

Where does the negative charge in alkaline buffers migrate towards?

Answer 2

Migrates toward the anode (+)

Question 3

Where does the positive charge in acid buffers migrate towards?

Answer 3

Migrates toward the cathode (-)

Question 4

What is the genetic abnormality in sickle cell disease?

Answer 4

Homozygous abnormality of beta globin chain

Glu to Val substitution at amino acid 6 of beta chain (beta6Val)

Question 5

What determines the extent of HbS polymerization?

Answer 5

Time and concentration dependent

Question 6

What are some factors that affect the concentration of HbS?

Answer 6

Percentage of hemoglobin S of total hemoglobin
Total hemoglobin concentration in the red cells (MCHC) – increased in states of cellular dehydration, decreased when there is co-existent thalassemia

Question 7

What are some clinical settings that predispose to sickling??

Answer 7

Hypoxia
Acidosis
Dehydration
Cold temps
Infections

Question 8

At what pressure do SS cells being to sickle?

Answer 8

~40 mm Hg

Question 9

What does the lifespan of an RBC become after it has been sickled?

Answer 9

20 days

Question 10

What are some effects of RBC sickling?

Answer 10

Chronic hemolysis

Microvascular occlusion with resultant tissue hypoxia and infarction

Question 11

Why are newborns with SS clinically fine? When do they begin to show symptoms?

Answer 11

High HbF levels at first

Show signs by about 10-12 weeks

Question 12

Some clinical manifestations of SS

Answer 12

Severe anemia
Acute pain crises
Auto-splenectomy
Acute chest syndrome
Strokes 
Aplast crisis (parvovirus B19_
Infections
Liver damage
Splenic sequestration crisis
Megaloblastic anemia
Growth retardation
Bony abnormalities 
Renal dysfunction
Leg ulcers
Cholelithiasis

Question 13

SS laboratory findings

Answer 13

Chronic anemia (about 7)
Increased bilirubin
Sickled cells, target cells and polychromasia
Increased reticulocytes
Normal MCV
Post-splenectomy changes in adults

Question 14

What is hemoglobin SC disease??

Answer 14

Hemoglobin C results from glu to lys substitution at the 6th amino acid of the beta globin chain
Generally milder than SS, but highly variable

Question 15

What is Hb S/Beta thalassemia?

Answer 15

Heterozygous Hb S with trans beta thalassemia allele –> decreased or absent normal beta chains
Clinically variable
Hb S > Hb A

Question 16

How does Hydroxyurea help to treat sickle cell disease?

Answer 16

Inhibits ribonucleotide reductase and causes cell cycle arrest
Increases erythrocyte levels of HbF, ameliorating the sickling manifestations

Question 17

What is HbC disease? (CC)

Answer 17

Glu to Lys substitution of aa 6 on beta chain
Cells abnormally rigid and dehydrated
RBC life span shorted to 30-35 days
NOT a sickling disorder

Question 18

What are some lab findings of individuals with HbC?

Answer 18

Hemoglobin 8-12
Numerous target cells
Mild microcytosis
Spherocytes
Occasional C crystals

Question 19

What are thalassemias?

Answer 19

Typically microcytic, hypochromic anemias of varying severity – d/t decreased Hb production (cytoplastmic maturation defect)
Excess normally produced globin chains accumulate and cause intramedullary cell death and/or decreased RBC survival

Question 20

Beta-Thal Major

Answer 20

Absent or marked decrease in beta chain production
Excess normal alpha chains which precipitate in normoblast and erythrocytes
Intramedullary cell death and decreased RBC lifespan
Severe anemia– baseline Hb of 2-3
Transfusion dependent

Question 21

Beta-Thal Minor

Answer 21

Heterozygous form 
Asymptomatic 
Mild to no anemia 
Microcytosis
Mild anisopoikilocytosis 
Basophilic stippling
Elevated HbA2

Question 22

Alpha-Thalassemia

Answer 22

Usually result of gene deletion

Question 23

Alpha-Thal

Silent carrier

Answer 23

1 alpha gene deleted

Question 24

Alpha-Thal trait

Answer 24

2 genes deleted

Mild microcytic anemia

Question 25

Hemoglobin H disease

Answer 25

3 alpha genes deleted
Mild-moderate, chronic hemolytic anemia
Hb H represents beta tetramers
Hb H soluble so does not initially ppt in normoblasts

Question 26

Hydrops fetalis

Answer 26

4 alpha genes deleted

Infants stillborn or die w/i few hours