Topic 4: Sideroblastic Anemia

Question 1

what is sideroblastic anemia?

Answer 1

a disorder of red blood cells (RBCs) that causes a microcytic anemia due to defects in the synthesis of protoporphyrin

Question 2

what’s the hallmark of sideroblastic anemia?

Answer 2

finding of ringed sideroblasts within the bone marrow

Question 3

What is the main cause of sideroblastic anemia?

Answer 3

due to defects in the synthesis of protoporphyrin

the heme portion of Hb is made of a protoporphyrin ring with an iron molecule in the middle

Question 4

where does the heme synthesis pathway happen?

Answer 4

within erythroblasts in the bone marrow

in the BM, macrophages transfer iron to erythroblasts

Fe then enters the RBC mitochondria and combines with protoporphyrin to form heme

mature erythrocytes do not have mitochondria!! so this process can only occur in the bone marrow where immature erythrocytes, which still have mitochondria, are present

Question 5

what’s the effect on the heme synthesis pathway when protoporphyrin is deficient?

Answer 5

usually macrophages in the BM transfer iron to erythroblasts where it enters the mitochondria and combines with protoporphyrin to form heme

with a protoporphyrin deficiency, the iron enters the mitochondria and builds up

Question 6

what does a bone marrow aspirate of sideroblastic anemia show?

Answer 6

you will see ringed sideroblasts– erythroblasts with granules of iron accumulating in rings around the nucleus

this is from iron building up in erythroblasts since there’s no protoporphyrin for it to combine with and make heme

this is the hallmark of siderobalstic anemia

Question 7

Why are ringed sideroblasts present in the bone marrow of patients with sideroblastic anemia?

Answer 7

Ringed sideroblasts are present because if protoporphyrin is deficient, iron builds up within the mitochondria in the developing erythroblast.

Iron then forms rings around the nucleus of erythrocytes, which is seen as blue accumulations on Prussian blue staining.

Question 8

why is there increased iron in the bone marrow in sideroblastic anemia?

Answer 8

1. there aren’t enough protoporphyrin rings for iron to bind to
2. when there’s a lot of iron around, the production of free radicals increases and RBCs undergo hemolysis within the bone marrow, leading to an increase in total iron

Question 9

what are the two general categories of causes of sideroblastic anemia?

Answer 9

1. congenital

2. acquired (more common)

Question 10

what is a congenital cause of sideroblastic anemia?

Answer 10

x-linked deficiency in ALA synthase in the heme synthesis pathway

Question 11

A deficiency of which vitamin may lead to sideroblastic anemia?

Answer 11

Vitamin B6 (pyridoxine) deficiency

Question 12

what are the acquired causes of sideroblastic anemia?

Answer 12

1. myelodysplastic syndrome
2. drugs
3. toxins
4. nutritional deficiencies

Question 13

what drugs can lead to sideroblastic anemia?

Answer 13

1. alcohol: interrupts heme synthesis
2. isoniazid: causes vitamin B6 deficiency
3. chloramphenicol: impairs mitochondrial protein
   synthesis
4. cycloserine

Question 14

what toxins can lead to sideroblastic anemia?

Answer 14

1. lead poisoning: inhibits ALA dehydratase and ferrocheletase
2. zinc overdose: causes a deficiency in copper via impaired absorption of copper in the colon

Question 15

what nutritional deficiencies can cause sideroblastic anemia?

Answer 15

1. pyridoxine/vitamin B6 deficiency: B6 needed for action of ALA synthase
2. copper deficiency

Question 16

what is the clinical presentation of sideroblastic anemia?

Answer 16

varies according to the underlying cause

Question 17

in what population is congenital sideroblastic anemia usually present?

Answer 17

young males

due to the X-linked inheritance pattern

Question 18

in what population is acquired sideroblastic anemia most common?

Answer 18

adulthood

Question 19

what will the CBC of a sideroblastic anemia patient look like?

Answer 19

• decreased Hb
• decreased Hct

MCV is usually low but it can also be normal or high….

Question 20

what is dimorphism?

Answer 20

seen on the blood smear of sideroblastic anemia

where you see two populations of cells: one normocytic group and one microcytic group!

so really, you can’t use the MCV to make your diagnosis, since it can be all over the place

Question 21

what do you see on the blood smear of sideroblastic anemia?

Answer 21

• dimorphism

- Pappenheimer bodies

Question 22

what are Pappenheimer bodies?

Answer 22

little iron deposits in red cells

they look like little blue granules usually in the periphery of the cell

Question 23

what do iron studies for sideroblastic anemia show?

Answer 23

• increased ferritin (total body iron stores)
• decreased TIBC
• increased serum iron
• increased % saturation

Question 24

what does the bone marrow in sideroblastic anemia look like?

Answer 24

displays erythroid hyperplasia

Prussian blue staining of the marrow aspirate will reveal ringed sideroblasts

Question 25

what are ringed sideroblasts?

Answer 25

erythroblasts with perinuclear granules of iron forming a ring or partial ring around the nucleus of the cell

Question 26

where will ringed sideroblasts be visible?

Answer 26

only in the bone marrow aka on a marrow aspirate!

they will NOT be seen on a blood smear

Question 27

how do patients counteract iron overload seen in sideroblastic anemia?

Answer 27

1. therapeutic phlebotomy

small amounts of blood are removed from the body to decrease the amount of iron

2. iron chelation therapy

drugs such as deferoxamine can be used to remove iron from the body

Question 28

What is the treatment for X-linked sideroblastic anemia?

Answer 28

supplementation with vitamin B6 (pyridoxine)

both congenital and acquired, respond well to Vitamin B6 supplementation