Hematologic Growth Factors

Question 1

Discuss the clinical use of iron.

Answer 1

It is given PO to prevent/tx iron deficiency anemia, particularly in pts with increased iron needs, s/p gastrectomy, and bleeding

Question 2

What increases iron absorption?

Answer 2

HCl and vitamin C

Question 3

Discuss the absorption of heme versus non-heme iron.

Answer 3

Heme iron (e.g. meat) is well absorbed. Non-heme iron (e.g. veggies) is bound to phytates which impair absorption, and it needs to be reduced to ferrous iron via ascorbate in order to be absorbed

Question 4

What is ferritin?

Answer 4

Storage form of iron

Question 5

What is transferrin?

Answer 5

It transports iron from mucosal cell to the tissues

Question 6

When do you see acute iron toxicity?

Answer 6

In children- necrotizing gastroenteritis, which requires whole bowel irrigation and deferoximin to chelate the iron

Question 7

When do we see chronic iron toxicity?

Answer 7

In hemochromatosis 2/2 excess iron deposits in organs leading to organ failure/death, requiring deferoxamine to chelate iron or phlebotomy

Question 8

What results in folic acid deficiency?

Answer 8

Megaloblastic anemia, and neural tube defects in newborns

Question 9

In what situations can folic acid deficiency occur?

Answer 9

The elderly (poor diet), ETOH, pregnant women, hemolytic anemia, malabsorption syndromes, renal dialysis, and some drugs (e.g. phenytoin, OCPs, and isoniazid)

Question 10

Discuss the pharmacokinetics of folic acid.

Answer 10

It is absorbed from fresh greens, yeast, liver, and fruits. Stored in the liver, excreted in urine and stool

Question 11

What is hydroxycobalamine and what happens when deficient?

Answer 11

Vitamin B12, deficiency causes megaloblastic anemia and neuro sx (e.g. parasthesia, weakness, ataxia, and specificity)

Question 12

Discuss the pharmacokinetics of hydroxycobalamine.

Answer 12

Usually administered parenterally. It is absorbed in the distal ileum via intrinsic factor, is transported bound to transcobalamin II, and is stored in the liver.

Question 13

Discuss the frequency of hydroxycobalamine administration based on replacement needs.

Answer 13

Daily to replenish stores.
Monthly for lifetime for maintenance.
Will see response within 48h

Question 14

What is epoetin alpha?

Answer 14

It is produced in mammalian cell expression system via recombinant DNA technology, and is also made by peritubular cells in the kidney in response to hypoxia, stimulating erythroid proliferation and differentiation, and inducing release of reticulocytes from the marrow.

Question 15

What are the adverse effects associated with epoetin alpha?

Answer 15

Htn and thrombotic complications, iron deficiency (almost all pts will need supplemental iron), hypertensive encephalopathy and seizure

Question 16

When do we give epoetin alpha?

Answer 16

In anemia d/t chronic renal failure and anemias w/ low EPO levels (e.g. AZT in HIV pts)

Question 17

Describe the mechanism of action of Darbepoetin.

Answer 17

It acts on progenitor cells to stimulate RBC production like epoetin.

Question 18

What adverse effects are associated w/ Darbepoetin?

Answer 18

It is generally well tolerated, but can increase BP in renal failure pts (hypertensive encephalopathy, seizures, increased CV events like MI/stroke/vascular access thrombosis), and rarely- rash and urticaria

Question 19

Describe the mechanism of action of G-CSF.

Answer 19

It stimulates progenitor cells committed to neutrophil lineage, and activates phagocytic activity of mature neutrophils. Mobilizes stem cells of all lineages into peripheral blood for easy collection of autologous stem cell transplantation.

Question 20

What is the clinical indication for G-CSF?

Answer 20

It is u sed in the tx of chemotherapeutic induced neutropenia, autologous stem cell transplantation (reduces time for engraftment and recovery from neutropenia)

Question 21

What adverse effects are associated w/ G-CSF?

Answer 21

It is better tolerated than GM-CSF, but can cause bone pain, local skin rxn at SC site, and splenomegaly

Question 22

Describe the mechanism of action of GM-CSF.

Answer 22

It stimulates proliferation and differentiation of granulocytic progenitor cells, and erythroid and megakaryocyte progenitors.

Question 23

What is the clinical indication for GM-CSF?

Answer 23

It reduces neutropenia after cytotoxic chemo, autologous transplantation (reduces time for engraftment and recovery from neutropenia).

Question 24

What adverse effects are associated with GM-CSF?

Answer 24

It is worse than G-CSF. Can cause fevers, flu-like sx, bone pain, diarrhea, malaise, arthralgias, myalgias. First dose- flushing, hypotension, n/v, dyspnea. Capillary leak syndrome w/ peripheral edema and pleural and pericardial effusions

Question 25

How are iron levels regulated?

Answer 25

By changes in absorption and storage