Kruse - Anemia and Hematopoietic Growth Factors

Question 1

Iron is absorbed as Fe__ state.

Iron is transported and stored in Fe___ state

Answer 1

• Absorbed: Fe2+ (ferrous) – ORAL

- Transported/Stored: Fe3+ (ferric); with transferrin – PARENTERAL

Question 2

Increased erythropoiesis is associated with an increase in number of ___-receptors on developing erythroid cells.

Answer 2

Transferrin

Question 3

Iron store depletion and iron deficiency anemia are associated with an increased concentration of serum ___.

Answer 3

Transferrin

Question 4

Iron is stored as ___.

Answer 4

ferritin

Question 5

In what states can iron be administered orally?

Answer 5

Administer as FERROUS salt (Fe2+): ferrous sulfate, ferrous gluconate, ferrous fumarate

Question 6

How should oral iron be administered (taken with…?)

Answer 6

water or juice on an empty stomach; may be admin with food to prevent irritation.

Question 7

Adverse effects of oral iron therapy.

Answer 7

N, epigastric pain, black stools, abdominal cramps, constipation, diarrhea (dose related; reduced if taken with or immediately after meals).

Question 8

Parenteral iron therapy is reserved for what type of pateints?

Answer 8

People unable to tolerate/absorb oral iron or with chronic anemia that can’t be maintained with oral iron (CRD, IBD, SI resection)

Question 9

Parenteral iron administration bypasses what regulatory mechanisms - beneficial why?

Answer 9

Bypasses iron storage regulatory mechanisms of the intestine – can deliver more iron than can can safely be stored.

Question 10

Name the three forms of parenteral iron is USA.

Answer 10

1. Iron dextran - (IV>IM), adverse effects - HA/fever/arthralgia/ N/V/back pain, flushing BRONCHOSPASM, ANAPHYLAXIS
2. Sodium ferric gluconate complex
3. Iron-Sucrose Complex

Question 11

What age is acute iron toxicity seen in? Symptoms?

Answer 11

Young children - see vomiting, abdominal pain, bloody diarrhea –> shock, lethargy, dyspnea –> metabolic acidosis, coma, death

Question 12

Treatment of acute iron toxicity.

Answer 12

Whole bowel irrigation and parenteral deferoxamine.

Question 13

Signs and symptoms of Chronic Iron Toxicity.

Answer 13

Deposits onto heart, liver, pancreas, etc = organ death.

Question 14

Treatment for Chronic Iron Toxicity.

Answer 14

Intermittent phlebotomy.

Oral iron chelator deferasirox.

Question 15

Two forms of active Vitamin B12 in humans + form of administration.

Answer 15

Cyanocobalamin and hydroxocobalamin - parenteral

Question 16

Most common clinical manifestation of B12 deficiency

Answer 16

Megaloblastic, macrocytic anemia.

Question 17

Describe the neurologic syndrome associated with B12.

Answer 17

Begins with paresthesias in peripheral nerves/weakness –> COT to spasticity, ataxia.

-homocysteine

Question 18

Richest dietary sources of folic acid.

Answer 18

Yeast, kidney, liver, green veggies.

Question 19

What is the clinical manifestation of folic acid deficiency?

Answer 19

Megaloblastic anemia.

Question 20

How does presentation of folic acid deficiency v. B12 deficency differ.

Answer 20

Both have megaloblastic anemia, but B12 has neuro syndrome and Folic Acid deficiency does not.

Question 21

Name four drugs that can cause folic acid deficiency.

Answer 21

• Inhibitors of DHFR: MTX, Trimethoprim, Pyrimethamine

- Phenytoin (long term)

Question 22

In what scenarios does EPO rise to induce erythropoiesis?

Answer 22

Anemia, hypoxemia, (kidney disease, marrow damage, iron deficiency, vitamin deficiency).

Question 23

Two erythrocyte-stimulating agents

Answer 23

Epoetin alpha and darbepoetin alpha

Question 24

Results of inducing erythropoiesis -

Answer 24

inc reticulocyte count (10 days), rise in Hct/Hb (2-6 weeks)

Question 25

Clincal scenarios when Erythropoiesis-Stimulating Agents are used.

Answer 25

Anemia (secondary to CKD or due to primary bone marrow disorders), AIDS, MM, MDS, MPD, etc).
Banned in professional athletes.

Question 26

Toxicity of ESAs

Answer 26

HTN, thrombotic complications (due to increase in blood)

Question 27

Function of myeloid growth factors

Answer 27

Enhance function of mature granulocytes and monocytes.

Question 28

Name two Granulocyte Colony-Stimulating Factors (G-CSF)

Answer 28

Filgrastim (recombinant human G-CSF) and pegfilgrastin (longer 1/2 life, administer less frequent)

(plerixafor)

Question 29

When is plerixafor used?

Answer 29

when patients respond suboptimally to G-CSF alone.
Use: filgrastim + plerixafor = inc. CD34+
Function - to increase HSC from marrow to PB

Question 30

Function of G-CSF

Answer 30

Stimulates proliferation and differentiation of progenitors already committed to the neutrophil lineage - activates phagocytic activity of mature neutrophils.

Question 31

Name a Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)

Answer 31

Sargramostim

Question 32

How does GM-CSF differ from G-CSF.

Answer 32

GM-CSF’s primary effect is to stimulate myelopoiesis (broader then G-CSF) - erythroid/megakaryocyte progenitors, mature neutrophil function, T-cell proliferation with IL-2

Question 33

Tx for cancer chemo-induced ***neutropenia

Answer 33

G-CSF accelerates neutrophil recovery

Question 34

Toxicity of Filgrastim and pegfilgrastim

Answer 34

bone pain

Question 35

Toxicity of GM-CSF

Answer 35

fever, malaise, arthralgia, myalgia, capillary leak syndrome (would see peripheral edema and pleural/pericardial effusion)

Question 36

What class of growth factor should be given for patients with thrombocytopenia?

Answer 36

Megakaryocyte growth factor.

Question 37

Name the two megakaryocyte growth factors.

Answer 37

Oprelvekin (IL-11) and Romiplostim (recombinant thrombopoietin)

Question 38

Clinical use for oprelvekin

Answer 38

Secondary prevention of thrombocytopenia in people receiving cytotoxic/myelosuppressive chemotherapy for NONmyeloid cancers - reduced # of platelet transfusions.

Question 39

Clinical use for romiplostim

Answer 39

Used to treat thrombocytopenia in people with chronic immune (idiopathic) thrombocytopenia purpura.
(ITP)

Question 40

AE of oprelvekin v. romplostim

Answer 40

• Oprelvekin - HA, dizziness, fatigue, CV, hypOk (all reversible)
• Romiplostim - mild HA

Question 41

MOA of oprelvekin

Answer 41

Activates surface cytokine receptors to stimulate growth of lymphoid/myeloid cells. Stimulate primitive megakaryocyte progenitors = inc. peripheral platelet and neutrophils.

Question 42

MOA of romiplostim

Answer 42

activates Mpl TPO receptor to cause dose dependent increase in platelet count.