Term
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Definition
hemoglobin < 13 g/dL (men)
hemoglobin < 12 g/dL (women) |
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Term
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Definition
hypoxia is sensed by the kidneys which release EPO into plasma
EPO induces hemoglobin formation
EPO also increases the rate of mitosis, stimulates stem cell differentiation, and increases release of retics from marrow |
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Term
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Definition
succinyl CoA + glycine yields heme + iron through the cofactor pyridoxine (B6)
heme + iron yields hemoglobin through the combination with alpha and beta protein chains |
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Term
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Definition
iron from diet is Fe3+ (ferric)
stomach acid reduces to Fe2+ (ferrous)
most iron we ingest is in the ferric form (Fe3+); must be converted to ferrous form (Fe2+) for absorption
diseases that cause decreased iron absorption: Crohn's disease
absorbed primarily in duodenum, some in jejunum
iron absorption decreased by:
phytates (found in grains), tannates (found in tea, coffee, wine), and phosphates
calcium
iron absorption increased by:
ascorbic acid
heme iron containing foods |
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Term
| recommended daily allowance of iron |
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Definition
8 mg adult male
8 mg post-menopausal female
18 mg menstruating females |
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Term
| how does iron get to the marrow? |
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Definition
cells present transferrin receptors when in need of iron
circulating transferrin typically 30% saturated with iron
in addition to delivering to bone marrow for use, transferrin delivers iron for storage in liver, marrow, and spleen as ferritin (quicker access) and hemosiderin (slower access, more stable) |
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Term
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Definition
[image]
EPO doesn't stimulate conversion per se, but actually prevents apoptosis (programmed cell death) of erythroid precursor cells allowing them to proliferate and mature
additionally EPO causes reticulocytes to be released earlier
peripheral erythrocyte is much larger than a mature erythrocyte b/c it has a nucleus in it |
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Term
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Definition
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Term
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Definition
chronic renal disease
other chronic diseases
iron, B12, pyridoxine, or folate deficiency
increased RBC destruction
accelerated loss of RBC mass
inadequate RBC production
infection
malignancy |
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Term
| general classification of anemia: deficiency, central, and peripheral |
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Definition
deficiency:
iron
vitamin B12
folic acid
pyridoxine
central:
anemia of chronic disease
malignancy
peripheral:
hemorrhage
hemolysis |
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Term
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Definition
[image]
dilutional anemia: increased plasma volume; RBC count can artificially go down |
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Term
| classification of anemias based on morphology: macrocytic |
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Definition
vitamin B12 deficiency
folic acid deficiency
alcoholism
liver disease
myelodysplasia
hypothyroidism |
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Term
| classification of anemias based on morphology: microcytic |
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Definition
iron deficiency
sickle cell
thalassemia
hemoglobinopathies |
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Term
| classification of anemias based on morphology: normocytic |
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Definition
blood loss
hemolysis
bone marrow d/o
renal failure
endocrine d/o
myeloplastic anemias
anemia of chronic disease
very difficult but common disorder to diagnosis
usually ACD presents with either slightly microcytic or normocytic cells with normal cell morphology on smears
may result from inability to release EPO, inactivity of EPO, inability for iron to escape macrophage binding, and general early mature cell death due to cytokines |
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Term
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Definition
symptoms:
decreased exercise tolerance
fatigue
dizziness
irritability
weakness
palpitations
vertigo
shortness of breath
chest pain
numbness
paresthesias
signs:
tachycardia
pale appearance (especially in conjunctivae, nailbeds)
decreased mental acuity
increased intensity of pre-existing murmors
iminished vibratory sense (in B12 deficiency)
hepatospleenomegaly
bruising, petechiae
lab tests:
decreased Hgb
decreased Hct
decreased RBC
decreased serum iron
ferritin levels - decreased in iron deficiency anemia; increased in anemia of chronic disease |
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Term
| differentiating symptoms: iron deficiency anemia |
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Definition
glossal pain
smooth tongue
reduced salivary flow
pica
pagophagia (ice) |
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Term
| differentiating symptoms: B12 deficiency |
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Definition
pale
icteric
numbness
paresthesias
peripheral neuropathy
ataxia
decreased vibratory sense
decreased deep tendon reflex
irritability
memory impairment
dementia
depression
NEUROLOGIC SYMPTOMS = B12 DEFICIENCY
oftentimes the neurologic manifestations of B12 deficiency anemia precede laboratory abnormalities |
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Term
| differentiating symptoms: folic acid deficiency anemia |
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Definition
| similar to B12 deficiency but NO neurological symptoms |
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Term
| normal range for hemoglobin |
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Definition
males 13.5-17.5
females 12-16 |
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Term
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Definition
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Term
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Definition
amount of hemoglobin per volume of whole blood
higher values seen in males
androgenic steroids stimulate RBC production
females experience blood loss during menses
rough estimate of tissue oxygenation |
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Term
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Definition
actual volume of RBCs in a unit volume of whole blood
usually 3 times the hemoglobin value
decreased Hct:
reduced number of RBC
reduced size of RBC
increased plasma volume |
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Term
| MEAN CORPUSCULAR VOLUME (MCV) |
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Definition
REPRESENTS THE AVERAGE VOLUME OF RBCS
FALSELY ELEVATED MCV WHEN:
RETICULOCYTOSIS (INCREASE IN RETICULOCYTES; CELLS ARE LARGER)
HYPERGLYCEMIA |
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Term
| mean corpuscular hemoglobin (MCH) |
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Definition
percent volume of Hgb in a RBC
MCH may be decreased when:
microcytic cell contain less Hgb
normocytic cell with abnormally low Hgb
MCH usually elevated when:
macrocytic cell can contain more Hgb |
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Term
| mean corpuscular hemoglobin concentration (MCHC) |
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Definition
the weight of Hgb per volume of cells
independent of the cell size
more useful in distinguishing microcytosis and hypochromia
DECREASED MCHC ALWAYS INDICATES HYPOCHROMIA
a microcyte with normal Hgb will have low MCH, but a normal MCHC
this can be a useful test if looking at microcytic anemias and distinguishing between Fe deficiency and hemoglobinopathies |
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Term
| total reticulocyte count (retic) |
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Definition
indirectly indicates new RBC production
1% of RBCs are replaced daily
1% of the body's total RBCs are reticulocytes
lack of reticulocytosis during anemia indicative of problems with RBC production
may be falsely elevated with Hct decreases and normal retic production
multiple retic % by patient's Hct, then divide by the average normal Hct
5% reticulocyte count means the body is trying to make more RBCs; could be due to blood loss (more likely) and malignancy |
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Term
| red blood cell distribution width (RDW) |
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Definition
the higher this index, the more variable the size of the RBC
can be helpful in the diagnosis of mixed anemias
presence of both iron deficiency and FA/B12 deficiency may result in microcytes and macrocytes yielding a normal MCV
most useful in evaulation of response to iron therapy (increased retic production)
reticulocytes are larger than mature erythrocytes
if a patient is responding to iron therapy, there should be a larger proportion of large cells in addition to small mature cells |
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Term
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Definition
can provide info on:
functional status of bone marrow
defects in RBC production
anisocytosis: variations in cell size
poikilocytosis: variations in cell shape |
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Term
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Definition
level indicates concentration of iron bound to transferrin
20-30% diurnal variation in serum iron levels (highest in the morning)
may be decreased by infection and inflammatory processes
may remain within normal levels as iron stores take a considerable amount of time to deplete
b/c of high intrapatient variability, serum iron should be assessed with TIBC (total iron binding capacity)
decreased in iron deficiency anemia and anemia of chronic disease, elevated in hemolytic anemias |
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Term
| total iron binding capacity (TIBC) |
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Definition
indirect measure of iron binding capacity of transferrin
little to no fluctuations within the day, or day to day
low Fe + high TIBC indicates IDA
low Fe + low TIBC indicates ACD
may be elevated with:
oral contraceptive use
pregnancy |
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Term
| percentage transferrin saturation |
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Definition
normally 20-50% saturated
< 15% in IDA
less specific and sensitive marker than ferritin
transferrin in and of itself often used as a means to assess hepatic function and nutritional status |
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Term
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Definition
concentration of STORED iron
best indicator of iron deficiency or iron overload
diagnostic of IDA as ferritin levels will only decrease in IDA, whereas serum iron may decrease in ACD too
chronic infection or inflammation may elevate levels |
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Term
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Definition
of questionable clinical utility
slow to respond to either pathology or replacement |
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Term
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Definition
B12 deficiency may exist prior to decrease in vitamin B12 levels due to tissue stores
may be false low with/during:
folate deficiency
pregnancy
oral contraceptive use
multiple myeloma |
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Term
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Definition
used to differentiate between FA deficiency anemia and B12 deficiency anemia
vitamin B12 required to convert methylmalonyl coenzyme A to succinyl coenzyme A
high MMA is diagnostic for B12 anemia but not affected by FA deficiency
loses utility in renal disease and hypovolemia due to decreased urinary excretion |
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Term
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Definition
used to diagnose B12 deficiency anemia
B12 absorption defects due to lack of intrinsic factor (i.e. pernicious anemia) |
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Term
| direct antiglobin test (DAT) or Coombs test |
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Definition
antiglobulin tests
direct Coombs test detects antibodies bound to erythrocytes
indirect Coombs test detects antibodies present in the serum
positive direct Coombs indicative of antibody mediated autoimmune hemolysis |
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Term
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Definition
must always rule out blood loss first
50% of IDA due to some form of GI bleeding
CDC recommends 30 mg/day for pregnancy women starting at first prenatal visit
classified as prelatent, latent, and iron deficiency anemia
prelatent: reduction in iron stores without reduced serum iron levels
latent: iron stores depleted but Hgb above lower limit of normal |
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Term
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Definition
dietary supplementation and iron preparations (meat, fish, poultry best)
recommend meat, orange juice, and other high iron and ascorbic acid containing foods
recommend limiting milk and tea or consuming in moderation
200 mg of elemental iron daily in 2-3 divided doses
titrat up to this dose to improve tolerability
few can tolerate this amount of iron due to GI ADRs
continue treatment for 3-6 months beyond resolution to allow for repletion of iron stores |
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Term
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Definition
ferrous iron salts available in numerous commercial products
little data to suggest one salt better absorbed than the other
administer 1 hour prior to meals
taking with food reduces absorption 50%
H2 antagonists and PPIs may impair iron absorption
ADRs include dark discoloration of feces, constipation or diarrhea, nausea, and vomiting
consider recommending taking with 250 mg ascorbic acid
ferrous sulfate contains ~ 65 mg of elemental iron
ferrous gluconate ~36 mg of elemental iron
ferrous sulfate is cheapest formulation and most widely used
side effects (mostly GI/constipation) are directly related to amount of elemental iron in each dose
if patient unable to tolerate ferrous sulfate, consider either switching to liquid and adjusting the dose as tolerable, or switching to ferrous gluconate
you may also have the patient take with food but this will greatly decrease absorption
enteric coated products may prevent dissolution prior to the site of maximal absorption (distal duodenum, proximal jejunum) |
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Term
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Definition
used in suspected inability to absorb iron
administer 50 mg elemental iron via liquid ferrous sulfate
draw serum iron levels q30 minutes for 2 hours
plasma levels should increase by > 50 mcg |
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Term
| oral iron drug interactions |
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Definition
drugs that decrease iron absorption:
Al, Mg, and Ca containing antacids
tetracycline and doxycycline
H2 antagonists
PPIs
cholestyramine
drugs affected by iron:
decreases levodopa
decreases methyldopa
decreases levothyroxine
penicillamine
fluoroquinolones
tetracycline and doxycycline (avoid within 2 hours of Fe administration)
mycophenolate |
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Term
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Definition
indicated when iron malabsorption or intolerance
no quicker resolution than oral
dextran preparations associated with anaphylactic deaths
parenteral iron may be released too quickly
overload transferrin binding
free iron reactions in plasma resulting in neutrophil dysfunction
iron dextran must be processed by macrophages prior to the iron being biologically available
dose (mL) = 0.0442 (desired Hgb-observed Hgb) X LBW + (0.26 X LBW)
LBW males 50 kg + (2.3 X inches over 5 ft)
LBW females 45.5 kg + (2.3 X inches over 5 ft)
test doses are recommended and product specific
just approved by FDA: ferumoxytol (Feraheme) - semi synthetic carbohydrate coated superparamagnetic iron oxide nanoparticle
may create false readings in MRI scan |
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Term
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Definition
reticulocytosis within 5-7 days
Hgb increases of 2-4 g/dL every 3 weeks
< 2 g/dL increase of 3 weeks necessitates further evaluation
TREAT UNTIL FERRITIN LEVELS CORRECTED FOR 3-6 MONTHS |
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Term
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Definition
B12 deficiency
folic acid deficiency
medications: hydroxyurea, zidovudine, methotrexate, cytosine, cladribine, sulfasalazine, azathioprine/6-mercaptopurine, sulfamethaxozole/trimethoprim
reticulocytosis
myelodysplastic syndromes and lymphocyte leukemia
lipid d/o associated with liver disease
alcoholism |
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Term
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Definition
| NEURO SIGNS MAY PRESENT FIRST |
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Term
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Definition
US government mandated fortification of all grain products
decrease incidence of neural tube defects
avoid masking vitamin B12 deficiency
recommended daily allowance of folic acid:
400 mcg daily in nonpregnant females
600 mcg daily in pregnant females
500 mcg daily in lactating females
treat with 1 mg FA daily x 4-5 months
history of baby with neural tube defects = 4 mg FA daily |
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Term
| anemia of chronic disease |
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Definition
essentially a diagnosis of exclusion
pathogenesis:
shortened erythrocyte survival
impaired marrow response
disturbance of iron metabolism (trapped in macrophages)
pathophysiology:
infections
inflammatory |
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Term
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Definition
exogenous erythropoetin (epoetin alfa, Epogen)
discontinue after Hct reaches 40%
must monitor iron levels closely as IDA may develop with continued EPO dosing - some practitioners just supplement Fe
Darbepoetin - synthetic erythropoetin
EPO drugs have shown to increase risk of stroke and MI
FDA has recommendations on dosing b/c there will be a delayed response - TREAT TO A TARGET HEMOGLOBIN OF 11, not higher!
black box warning on both - serious cardiovascular risks, tumor progression, increased mortality, thrombotic events |
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Term
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Definition
indicated with Hgb falls to 8-10
must weigh risks and benefits
assess symptoms |
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Term
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Definition
intrinsic:
membrane defects - spherocytosis, elliptcytosis
hemoglobin defects - sickle cell disease, thalassemia
metabolic defects - glucose-6-phosphate dehydrogenase deficiency
extrinsic:
autoimmune dysfunction |
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Term
| anemia associated with malignancy |
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Definition
consider 2 specific etiologies:
anemia associated with malignancy
anemia associated with myelosuppressive chemotherapy
much debate over appropriate treatment:
transfusions to maintain Hgb levels
erythropoesis stimulating agents? - higher mortality in certain cancer types; numerous position statements with varying recommendations
EPO ARE INDICATED FOR ANEMIA INDUCED BY CHEMOTHERAPY OR RADIATION; NOT INDICATED FOR ANEMIA INDUCED BY CANCER
ESAs are not indicated for anemia unrelated to chemotherapy
for anemia related to myelosuppressive chemotherapy, ESAs are not indicated if the cancer treatment goal is cure
ESAs may be appropriate for anemic patients receiving palliative myelosuppressive chemotherapy who do not need immediate correction of anemia |
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