Thalassemias (DiPaola L1)

Question 0

Which Hb genes are primarilly expressed as a fetus? (week 6 - birth)

Where are the Hb produced during fetal life?

Answer 0

alpha
gamma (beta-like)
HbF
Liver–> Spleen–> Bone Marrow

Question 1

Which hemoglobin genes are expressed in the first few weeks of life? (0 - 6 wks)
Where is is produced?

Answer 1

Epsilon (beta-like)
Zeta (alpha-like)
–> Gower 1, Gower 2, Portland
yolk salk

Question 2

Which Hb genes are primarily expressed after birth?
Where is this Hb produced?

Which Hb is expressed in small amounts after birth?

Answer 2

Primarily
alpha & beta
Bone Marrow

small amts: gamma

Question 3

What does the delta (beta-like) Hb gene do?

Answer 3

produced in very small amts as an adult
likely a evolutionary remnant
HbA_2

Question 4

What are the structural hemoglobinopathies?

What sort of mutations cause these?

Answer 4

Point mutations
HbS Glu6Val
HbC Glu6Lys
HbE Glu26Lys

Question 5

HbS

loss of function? gain? etc?

Answer 5

Novel Function

polymerization of the Hb molecules

Question 6

What is the histological change that you see in HbC?

What is the clinical presentation?

Answer 6

Crystalization of the hemoglobin in a blood smear.
Can get more infections (give penicillin)

often called HbC trait b/c no other symptoms

Question 7

According to the formal definition of Thalassemia, what is the problem?

Answer 7

reduced rate of production of one or more chains of Hb.
** abnormal ratio of Hb chain production
defective Hb production & damage to the red blood cells and their precursors

Question 8

What deletion causes HbH?

Answer 8

3-gene deletion of Hb alpha

Question 9

What deletion(s) cause alpha thalassemia trait?

Answer 9

alpha-thal 1: deletion of both alphas on one homologue

alpha-thal 2: deletion of one alpha on each homologue

Question 10

Which alpha hemoglobin gene deletion is clinically insignificant?

Answer 10

if only one of the 4 alpha genes is deleted.

Question 11

What is Gamma thalassemia?

Answer 11

clinically significant only at birth; no longer a problem at about 6 months of age.
Gamma Hb is a beta-like Hb so eventually beta proper will take over and the gamma deletion is not a problem.

Question 12

What is delta thalassemia?

Answer 12

By itself is not a problem because delta is a beta-like hb so beta will take over anyway.

if, however you have a delta-beta deletion, now its a problem.

Question 13

What are normal Hb levels?

Answer 13

all units are gm/dL
Newborns:  17-22
1 week: 15-20
1 month: 11-15
children: 11-13
adult male: 14-18
adult female: 12-16
geriatric male: 12.4 - 14.9
geriatric female: 11.7 - 13.8

So basically if you have in the single digits its Low, upper teens (dep on gender) or higher is High

Question 14

What is the reticulocyte count and a normal value?

Answer 14

immature red blood cells
blood levels should be low 1-3%

0 is bad and higher levels indicate lots of red blood cell production

Question 15

What is microcytic and what lab values would indicate this?

Answer 15

low red blood cell counts
MCV (mean corpuscular volume) should be around
76 - 100 fL

Question 16

What is Cooleys anemia?

Answer 16

beta-thal major
2 severely abnormal or absent beta genes
severe anemia, low MCV count, transfusion dependent
x-ray shows dense marrow expansion in the skull bone changes b/c making marrow in as much bone as you can –> fractures
enlarged spleen & liver
iron overload- body absorbs more b/c trying to make more blood cells

Question 17

If a pt. is transfusion dependent, what sort of other treatments are indicated?

Answer 17

iron chelation
vitamin C (assists in chelation)
spelenectomy / cholecystectomy
bone marrow transplant

Question 18

What does the RDW in a CBC tell you and what are normal values?

Answer 18

RDW = red cell distribution width
variability in the size of red blood cells
normal variation values: 11.5 - 14.5%