Hematologic agents Flashcards
Bone marrow production
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
What is erythropoietin?
endogenous glycoprotein that regulates RBC production
Serum EPO concentrations at birth
decrease following birth to reach nadir at 4-6 weeks. By 10-12 months they reach adult levels
Serum EPO concentrations in preterm
fall of EPO is more profound and persists longer contributing to anemia of prematurity
Does EPO cross the placenta
No
Production of EPO is stimulated and regulated by
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
How does EPO maintain RBC production
inhibiting apoptosis of erythroid progenitors and stimulating their proliferation and differentiation into normoblasts.
Recombinant EPO indications
used to treat or prevent anemia due to renal failure and prematurity
Anemia of prematurity clinical trail
suggests combination of iron supplementation and rEPO
Hyporegenerative anemia of neonates with Rh-hemolytic disease clinical trial
mixed results
Anemia of BPD clinical trial
Infants received 200 U of rEPO per day for 10 days and showed increased retics, hct, fewer transfusions
CHD clinical trial
Neonates awaiting transplant received 200 U per day and had significant increase in hct and decrease in transfusions
What must be given concurrently with rEPO
Iron 6-8 mg/kg/day
Recommended doses of rEPO
SQ 400 U/kg 3 times per week for 2 wks
IV 200 U/kg every day for 2 wks
Aranesp
Erythropoiesis stimulating protein, single once a week injection but very few studies done
Adverse effects of rEPO
several in adults, none in neonatal studies
rEPO and ROP
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
Side effect of rEPO
potential effect on iron balance
Beneficial side effects: inc erythropoiesis and megaryocytopoiesis.
Fe and the neonate
increase risk for deficiency bc bulk of Fe transfer occurs in 3rd trimester.
Fe
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
Excessive Fe intake
common cause of poisoning death in less than 6 yrs of age in US
Supplementation
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
G-CSF
granulocyte colony stimulating factor: physiologic regulator of neutrophil production and function
rG-CSF has an effect on what?
white cell maturation and function
Enhancement of neutrophils functions:
chemotaxis, phagocytosis, superoxide production, bactericidal activity
rG-CSF and bacterial sepsis trial
Does appear to increase circulating neutrophil counts but unclear whether there is clinical benefit. No significant side effects reported
rG-CSF and PIH trials
suggests that it could be useful
rG-CSF and alloimmune neutropenia trials
Good results when given and response evident in 24-48 hours
rG-CSF and autoimmune neutropenia trials
good results when given
rG-CSF and chronic idiopathic neutropenia
Can respond but usually remits after 3-6 months so tx may not be necessary
Adverse effects of rG-CSF rare and include:
thromobocytopenia, osteoporosis
CONTRAINDICATED WITH HYPERSENSITIVITY TO E-COLI DERIVED PROTEINS
What is rGM-CSF
Recombinant granulocyte- macrophage colony stimulating factor: increases neutrophil counts and may decrease mortality due to sepsis.
Significant increase in ANC with 48 hours
