Microcytic Anemia - Thalassemia

Question 1

How do we characterize thalassemia?

Answer 1

Decreased production of globin chain

Question 2

What type of mutations are we dealing with in thalassemia and what are carriers protected against? Also, what are the normal types of hemoglobin?

Answer 2

Inherited mutaiton disease
Plasmodium falciparum malaria
HbF alpha2gamma2
HbA alpha 2 beta 2
HbA2 alpha 2 delta 2

Question 3

Alpha thalassemia is usually due to what?

Answer 3

Gene deletion. There are 4 alpha genes on chromosome 16.

Question 4

What is the effect of a one gene deletion disease?

Answer 4

Asymptomatic

Question 5

What is the effect of a 2 gene deletion disease? What are the two types?

Answer 5

Mild anemia and increase in RBC
If its cis, could be bad news for offspring. Cis is also seen in asians.
If its trans, see it in Africans.

Question 6

What is the effect of three gene deletion?

Answer 6

Severe anemia because beta chains form tetramers and damage the RBCs.

Question 7

What is the effect of 4 gene mutation?

Answer 7

Lethal in utero because gamma chains from tetramers that damage RBCs and lead to fetal hydrops

Question 8

What is the cause of beta thalassemia and what two ethnicities more commonly get it?

Answer 8

Gene mutation unlike alpha that was gene deletion. Two genes are present on chromosome 11 and if you knock out production we call it Beta0 and if you have decreased production we call it beta +.
African and Mediterranean

Question 9

What is a key electrophoresis finding for B/B+, what is the severity of this disease?

Answer 9

Mildest form of the disease

Increased HbA2

Question 10

What is the major form of beta thalassemia and what does it present with?

Answer 10

B0/B0

Severe anemia a few months after birth because fetal hemoglobin is protective for awhile.

Question 11

What is the effect of not having beta chains?

Answer 11

Alpha chains cant hook up with them so they damage the RBCs. Also, the spleen recognizes the precipitate and leads to extravacular hemolysis.

Question 12

What happens because of the massive anemia?

Answer 12

Intense erythroid hyperplasia

1. Expanding RBC production to skull (crewcut appearance on x ray) and face (chipmunk face)
2. Extramedullary blood production in liver and spleen
3. Risk of aplastic crisis because of parvovirus 19 (remember this basically shuts down RBC production and these patients depend on every RBC they can get).

Question 13

What do these patients require pretty frequently, what is an identifying feature on smear of these patients with beta thal major, and what is lacking on electrophoresis?

Answer 13

Chronic transfusions, leading to secondary hemochromatosis
Target cells, the white parlor center has a red spot from hemoglobin
HbA