Hematologic Flashcards
the bone marrow of a healthy fetus produces _________ of cells every day
Billions
What is the challenge of the bone marrow in a fetus vs. an adult?
The marrow must produce enough cells to maintain a stable cell number per body mass as the infant grows
Preterm birth is a/w additional hematologic stressors which can result in _______ or __________
Anemia
Neutropenia
What is Erythropoetin?
Glycoprotein that regulates erythrocyte production (RBC’s).
What is the pathway of erythropoetin synthesis in the fetus/NB?
Yolk sac–>Liver–>Kidneys
Where is Epo production much of fetal life?
Liver
When does Epo production change to the kidneys?
Around time of birth
Epo maintains RBC production by inhibiting ______ of erythroid progenitors and stimulating their _________ & ________ into normoblasts
Apoptosis
Proliferation & Differentiation
Does EPO cross the placenta?
No, Fetus produces their own
To maintain the increase in RBC volume a/w fetal growth, it is estimated ______ erythrocytes/day must be produced
50 x 10 to the 9th power
Erythropoetin production is stimulated by ________ induceable Factor __ & __, and regulated by ______ requirements for oxygenation
Hypoxia
Factor 1 & 2
Tissue requirements
In healthy, term infants, serum erythropoetin concentrations reach Nadir between ___-___wks.
By ___-___ wks, they reach adult concentrations.
4-6 wks
10-12 wks
In preterm infants, the fallen erythropoetin is more _______ and lasts ______—>what?
profound
longer
Anemia of prematurity
What does rEPO stand for?
Recombinant EPO (the med)
What medication is widely used to treat or prevent Anemia due to a variety of causes including Renal failure and prematurity?
rEPO
Name the 4 clinical trials w/EPO currently under way
- Anemia of prematurity
- Anemia from Rh-hemolytic Dz
- Anemia of BPD
- CHD
Name the other medication that is an erytrhopoesis stimulating protein.
Advantages?
Disadvantages?
- Aranesp
- Single 1x/wk injection
- Well-studied (in adults)
- Very few studies in preterm or term babies re: Pharmacokinetics, efficacy, risks/benefits of use
What other med must be given w/EPO?
Iron
Neonates require ______ dosing of rEPO/kg and more _______ dosing to achieve an equivalent hematopoetic repsonse r/t…?
Higher
Frequent
Increased plasma clearance, high vol. of distribution, short fractional elimination time
Garcia et. al showed that for doses at _____ u/kg/wk rEPO, the average # tranfusions per pt decreased by 3/4 of a transfusion.
500 u/kg/wk
What lab level may be helpful in assessing Fe stores?
Ferritin
What are the adverse effects of rEPO in adults?
Hypertension, thrombus formation, polycythemia, red cell aplasia
Early, high-dose rEPO may have a _______ effect on the retina by ameliorating the first stage of ROP .
Protective effect
–but one study suggested an increased risk of ROP in pts started on early high-dose rEPO and Iron.
In 2008, the FDA put out a warning for pts getting rEPO at higher than recommended doses w/what Dz?
What were the effects?
Chronic Kidney Failure
Increased risk blood clots, stroke, death
In preterm infants, rEPO for treatment of Anemia has been very ____ with ____ adverse side effects of adults.
Safe
none
What is a potential side effect of EPO?
an effect on Iron balance
Preterm babies are at risk for Iron deficiency r/t …?
Bulk of Iron transfer is during 3rd trimester
Iron is required for normal ______ & _______
growth and development
Iron deficiency can lead to?
Adverse Neurodevelopmental consequences: Deficits in executive function & memory
T/F: Administration of Iron in the 1st 2 weeks of life is NOT advised d/t potential oxidative effects in the face of deficient anti-oxidant mechanisms.
True
The actual side-effects of rEPO are what we are __________ to see-including:
Hoping
Increasing Erythropoesis
Possible Megakaryocytopoesis
What is a nutritional source of highly bio-available Iron?
Breastmilk
Iron is a required mineral in transfer of _____from the lungs to the tissues for storage for use during muscle contraction.
Oxygen
Iron contained in cow’s milk is less well ___________.
Absorbed-a reason it is not recommended until 1 yr/life
Iron is found as _____ iron in animal-based foods (meats). This is the most ____-______ form vs. plant-based (grains, fruits, vegetables)
Heme iron
Bio-available
Preterm formulas only provide ___ mg/kg/day iron. Supplemental iron is required
1.8 mg/kg/kday
____ overdose is the most common cause of poisoning death in children
Iron
6 y/o
Endogenous Iron stores are used up by ___ months of age.
6 months
Preterm, LBW, & breastfeeding: Iron supplement via gtts at ____ mg/kg/day. Start __-__ wks/age until 12 months.
2 mg/kg/day
2-4 wks/age
Healthy, term breastfeeding babys: supplement w/___ mg/kg/day iron.
Starting at __-__ months add iron from complimentary foods.
1 mg/kg/day
4-6 months
Infants < 12 months should be given only ___ fortified formulas.
Iron-fortified
What other possible effects might EPO have?
Neuroprotection
Protection of other organs: Heart, Kidneys
Fer-in-sol supplement provides more/less iron per dose than multi-vitamin product?
More~25 mg/mL vs. 10 mg/mL
Studies show children Anemic in early childhood continue to have _____ ________ & motor development and depressed school achievement into middle childhood.
Poor Cognitive
What does G-CSF stand for?
Granulocyte Colony Stimulating Factor
G-CSF is a physiologic _______ of ______production and function.
Regulator of Neutrophil
G-CSF has multiple effects on what type of cell’s maturation and function?
WBC
How does G-CSF enhance Neutrophil functions?
Chemotaxis
Phagocytosis
Superoxide Production
Bacteriocidal activity
Administration of G-CSF has long been used to prevent _______ in pts w/non-myeloid malignancies receiving Anti-CA drugs and suffering Febrile Neutropenia.
It is also used to supplement _________after bone marrow transplant.
Infection
Recovery
Name the 5 G-CSF clinical trials in process
- Infants w/bacterial sepsis
- Infants whose mothers had PIH
- Alloimmune Neutropenia
- Autoimmune Neutropenia
- Chronic Idiopathic Neutropenia
What are the 3 adverse effects (rare) of G-CSF?
- Thrombocytopenia
- Osteoporosis
- Contrandicated w/known hpersensitivity to e-coli derived proteins or any components of the product.
What is rGM-CSF?
Recombinant Granulocyte Macrophage Colony Stimulating Factor
What does rGM-CSF do?
Increases Neutrophil counts and may decrease mortality due to sepsis when used prophylactically.
–Significant increase in ANC w/in 48 hrs of administration.
Name the 2 clinical trials w/rGM-CSF?
- Neonatal sepsis
2. Prophylaxis against Nosocomial Infections
What adverse effects are there w/rGM-CSF?
What is needed?
No serious adverse effects reported
Long-term studies needed.
