Hematopoietic Growth Factors

Question 1

What are 3 main growth factors for erythrocytes?

Answer 1

• IL-1, IL-6, IL-3
• G-CSF
• GM-CSF
• **Epoetin **

Question 2

What is the best source of dietary iron?

Answer 2

meat (heme iron)

*Vegetables not as good. Non-heme iron in foods must be reduced to ferrous iron: usually ascorbate aids this *

Question 3

Which form of iron is absorbed?

Answer 3

Only the ferrous (Fe+2) form is absorbed.

Both vitamin C and HCl will increase absorption.

Question 4

What determines the body’s iron content?

Answer 4

Absorption

Storage = ferritin

Transferrin transports iron from mucosal cell to the tissues. Duodenum and prox. jejunum.

Question 5

How is iron eliminated?

Answer 5

No excretion mechanisms

Regulation of iron balance is achieved by changing absorption and storage of iron.

Question 6

What happens if body iron stores are high ?

Answer 6

stored as ferritin

Question 7

What happens if body iron stores are low?

Answer 7

iron is transported to bone marrow for hemoglobin production.

Question 8

What happens with apoferritin if free iron is low?

Answer 8

synthesis is inhibited and iron binding shifts to transferrin

Question 9

What happens with apoferritin if free iron is hi?

Answer 9

synthesis is stimulated and iron is sequestered as ferritin and organs are protected from iron’s toxic effects.

Question 10

What happens in acute iron toxicity?

Answer 10

Necrotizing gastroenteritis

Treatment = bowel irrigation, Deferoximine- to chelate iron that has been absorbed and to promote excretion, Supportive care

Question 11

Chronic toxicity

Answer 11

Treated with phlebotomy or chelation therapy

Question 12

What is the most common form of iron?

Answer 12

Ferrous sulfate is the most common, but most GI side effects. Ferrous gluconate is less.

Question 13

When is iron dextran given?

Answer 13

Reserved for patients that cannot tolerate oral iron or cannot absorb it. Give IV or IM

Question 14

Function of vitamin B12

Answer 14

Dietary folate is absorbed. A methyl group gets removed by vit. B 12. It donates it to methionine, an important AA to be a methyl donor and essential aa . . . which then gets metabolized to S adenosyl (makes norepi from epi).

N5/N10 methyeleneTHF, catalyzes dUMP, dTMP which goes on to DNA synthesis. If you can’t make DNA, you can’t make cells (RBCs)

Question 15

How is B 12 transported?

Answer 15

Transported bound to transcobalamin II; excess vitamin stored in liver

Question 16

Correcting a B12 anemia with folic acid

Answer 16

Large amounts of folic acid can correct the anemia due to Vitamin B12. **BUT it Cannot correct the neurologic damage. **

Question 17

How is vit B12 administered?

Answer 17

Given by parenteral injection usually as hydroxycobalamin- remains in the circulation longer.

• To replenish stores given daily
• Maintenance dose- once per month for lifetime
• Hematologic response is rapid: marrow returns to normal within 48 h.

Question 18

What’s the recommended intake for folic acid?

Answer 18

400 mcg per day
Pregnant or lactating women 500-600 mcg, Prevention of neural tube defects 400 mcg per day

Question 19

How soon can anemia develop with folic acid deficiency?

Answer 19

Anemia can develop in 1-6 mo after dietary intake has diminished

Question 20

How is folate absorbed?

Answer 20

Reduced methylated monoglutamates are absorbed. Stored in cells as the **polyglutamate **

Question 21

Folates in pills

Answer 21

Folic acid = Pteroylglutamic acid

Folinic acid- 5- formyltetrahydrofolate = Leucovorin-rescue from high dose methotrexate therapy

Question 22

What is the dosage for folic acid deficiency?

Answer 22

1 mg per day

reversal of deficiency within 1-2 months

Question 23

Epoetin Alpha

Answer 23

Glycosylation patterns in the recombinant protein is different from that produced by body and can be distinguished using modern assay methods.

**Not cleared by dialysis
Liver major site of degradation **

Question 24

List 4 functions of Epoetin alpha

Answer 24

1. Made in response to tissue hypoxia
2. Target cells- CFU-E
3. Stimulates erythroid proliferation and differentiation
4. Induces release of reticulocytes from marrow

Question 25

4 adverse effect of epoetin alpha

Answer 25

1. HTN and thrombotic complications
2. Iron deficiency
3. HTN encephalopathy
4. Seizures

Question 26

darbepoetin alpha

Answer 26

Acts on progenitor cells to stimulate red blood cell production like epoetin. Four amino acids in epoetin have been mutated such that additional carbohydrates can be added.

Clearance is slowed and the half life is 2-3 times longer than epoetin: Can be given weekly or every three weeks

Question 27

When do you have an increase in CV events with Darbepoetin?

Answer 27

associated with Hb increases > 1 g/dL in a 2 week period

Question 28

Where are G-CSF and GM-CSF produced?

Answer 28

bacterial or yeast expression systems

Question 29

What’s the difference between G-CSF and GM-CSF?

Answer 29

G-CSF = Stimulates progenitor cells already committed to the neutrophil lineage

GM-CSF = Stimulates proliferation and differentiation of granulocytic progenitor cells as well as erythroid and megakaryocyte progenitors

Question 30

Which hematopoietic growth factor is better tolerated?

Answer 30

G-CSF

Question 31

What can cause Capillary leak syndrome ?

Answer 31

GM-CSF