Hematologic agents

Question 1

Bone marrow production

Answer 1

produces billions of cells each day, marrow must produce enough cells to maintain a stable cell # per body mass as infant grows. Prematurity —- anemia and neutropenia

Question 2

What is erythropoietin?

Answer 2

endogenous glycoprotein that regulates RBC production

Question 3

Serum EPO concentrations at birth

Answer 3

decrease following birth to reach nadir at 4-6 weeks. By 10-12 months they reach adult levels

Question 4

Serum EPO concentrations in preterm

Answer 4

fall of EPO is more profound and persists longer contributing to anemia of prematurity

Question 5

Does EPO cross the placenta

Answer 5

No

Question 6

Production of EPO is stimulated and regulated by

Answer 6

Stimulated by hypoxia inducible factors 1 and 2 and regulated by requirement of tissue oxygenation BODY SENSES IT NEEDS MORE OXYGEN SO EPO STIMULATED TO MAKE MORE RBC’s TO CARRY OXYGEN TO BODY

Question 7

How does EPO maintain RBC production

Answer 7

inhibiting apoptosis of erythroid progenitors and stimulating their proliferation and differentiation into normoblasts.

Question 8

Recombinant EPO indications

Answer 8

used to treat or prevent anemia due to renal failure and prematurity

Question 9

Anemia of prematurity clinical trail

Answer 9

suggests combination of iron supplementation and rEPO

Question 10

Hyporegenerative anemia of neonates with Rh-hemolytic disease clinical trial

Answer 10

mixed results

Question 11

Anemia of BPD clinical trial

Answer 11

Infants received 200 U of rEPO per day for 10 days and showed increased retics, hct, fewer transfusions

Question 12

CHD clinical trial

Answer 12

Neonates awaiting transplant received 200 U per day and had significant increase in hct and decrease in transfusions

Question 13

What must be given concurrently with rEPO

Answer 13

Iron 6-8 mg/kg/day

Question 14

Recommended doses of rEPO

Answer 14

SQ 400 U/kg 3 times per week for 2 wks

IV 200 U/kg every day for 2 wks

Question 15

Aranesp

Answer 15

Erythropoiesis stimulating protein, single once a week injection but very few studies done

Question 16

Adverse effects of rEPO

Answer 16

several in adults, none in neonatal studies

Question 17

rEPO and ROP

Answer 17

Early high doses may have protective effect on retina in 1st stage of ROP
one study suggested increased risk of ROP when started on early high does rEPO with iron

Question 18

Side effect of rEPO

Answer 18

potential effect on iron balance

Beneficial side effects: inc erythropoiesis and megaryocytopoiesis.

Question 19

Fe and the neonate

Answer 19

increase risk for deficiency bc bulk of Fe transfer occurs in 3rd trimester.

Question 20

Fe

Answer 20

Mineral required for transfer of oxygen from lungs to tissues and storage of oxygen for use during muscle contx.
Essential for normal growth/development
important component for proteins and enzymes required for oxygen transport, cell division, neural transmitter synthesis, myelination and cellular oxidative metabolism

Question 21

Excessive Fe intake

Answer 21

common cause of poisoning death in less than 6 yrs of age in US

Question 22

Supplementation

Answer 22

Important! BUT NOT BEFORE 2 WEEKS!

Endogenous stores depleted by 6 months
Breastfed: 1 mg/kg/day starting 4-6 months
Preterm: 2 mg/kg/day starting 2-4 weeks till 12 months

Question 23

G-CSF

Answer 23

granulocyte colony stimulating factor: physiologic regulator of neutrophil production and function

Question 24

rG-CSF has an effect on what?

Answer 24

white cell maturation and function
Enhancement of neutrophils functions:
chemotaxis, phagocytosis, superoxide production, bactericidal activity

Question 25

rG-CSF and bacterial sepsis trial

Answer 25

Does appear to increase circulating neutrophil counts but unclear whether there is clinical benefit. No significant side effects reported

Question 26

rG-CSF and PIH trials

Answer 26

suggests that it could be useful

Question 27

rG-CSF and alloimmune neutropenia trials

Answer 27

Good results when given and response evident in 24-48 hours

Question 28

rG-CSF and autoimmune neutropenia trials

Answer 28

good results when given

Question 29

rG-CSF and chronic idiopathic neutropenia

Answer 29

Can respond but usually remits after 3-6 months so tx may not be necessary

Question 30

Adverse effects of rG-CSF rare and include:

Answer 30

thromobocytopenia, osteoporosis

CONTRAINDICATED WITH HYPERSENSITIVITY TO E-COLI DERIVED PROTEINS

Question 31

What is rGM-CSF

Answer 31

Recombinant granulocyte- macrophage colony stimulating factor: increases neutrophil counts and may decrease mortality due to sepsis.
Significant increase in ANC with 48 hours