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Spring Therapeutics Exam #1 - Anemias
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86
Health Care
Graduate
03/29/2010

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Term
anemia
Definition
below normal concentration of Hb in body;
Men: Hb <13 mg/dL
Females: Hb <12 mg/dL
Results in reduction of O2 carrying capacity of blood --> decreased Hb or decreased # of RBCs
Term
Consequences of Chronic Anemia
Definition
decreased quality of life;
decreased survival;
increased risk of cardiac complications
Term
Vitamin B12 deficiency & folic acid deficiency anemias
Definition
macrocytic megaloblastic anemias
Term
iron-deficiency anemia, sickle cell anemia, thallassemia
Definition
microcytic hypochromic anemias
Term
recent blood loss, hemolysis, bone marrow failure, anemia of chronic dx, renal failure anemia
Definition
normocytic anemias
Term
erythropoeitin (EPO)
Definition
90% produced in kidneys;
initiates & stimulates production of RBCs;
MoA: prevents apoptosis of erythroid precursor cells to allow for proliferation & subsequent maturation;
Decrease in tissue O2 conc. --> increase in production of this & release into plasma
Term
7-10 days
Definition
time it takes for entire process of formation of RBCs from erythroid precursor cells
Term
120 days
Definition
normal survival time of RBCs
Term
Patient Evaluation of Personal History for Diagnosis
Definition
Evaluate pt hx, PhEx/clinical presentation, & Lab tests;
Duration of anemia, family hx, social hx, exposure to toxic chemicals, menstrual hx, bowel hx, renal & hepatic dx, diet, previous blood transfusions, peptic ulcers, GI tract malignancies
Term
Clinical Presentation of Acute-Onset Anemias
Definition
tachycardia (decreased systemic vascular resistance w/ severe intravascular blood loss);
lightheadedness; palpitations;
angina; hypotension; dyspnea
Term
Clinical Presentation of Chronic Anemia
Definition
Present after 1-2 months:
weakness; fatigue; HA; vertigo;
faintness; symptoms of HF;
sensitivity to cold; loss of skin tone & pallor;
May initially present as asymptomatic
Term
Initial Lab Evaluation
Definition
CBC w/ Hb, Hct, WBC count, & platelets;
RBC count & MCV; Peripheral smear;
Stool sample for occult blood;
Term
Hemoglobin (Hb)
Definition
Males: 14-17.5 g/dL;
Females: 12.3-15.3 g/dL;
An estimate of O2 carrying capacity of blood.
Term
Hematocrit (Hct)
Definition
Males: 42-50%
Females: 36-45%;
Decreased Hct --> decrease in # of RBCs or an increase in plasma volume
Term
Serum iron
Definition
50 - 150 mcg/dL;
Concetration of iron bound to transferrin;
Decreased in IDA & anemia of chronic dx;
Term
Total Iron Binding Capacity (TIBC)
Definition
250-410 mcg/dL;
measures capacity of transferrin to bind to iron;
Usually higher when Fe stores are low;
Term
Transferrin Saturation (TSAT)
Definition
30-50%;
= (serum Fe/TIBC) x 100;
Reflects extent to which Fe-binding sites are vacant on transferrin & indicates amount of Fe readily available for erythropoeisis;
Term
Serum Ferritin
Definition
<10 - 20 mcg/L;
Indicates amount of Fe stored in liver, spleen, and bone marrow cells;
Best indicator of Fe deficiency or iron overload;
Term
Folic Acid
Definition
Plasma: 3.1-12.4 ng/mL;
RBC: 125 - 600 ng/mL;
Decreased levels = Folate deficiency megaoloblastic anemia
Term
Vitamin B12
Definition
180 - 600 pg/mL;
Used to determine vitamin B12 deficiency;
May be falsely low in folate deficiency, pregnancy, & oral contraceptives use
Term
Goal of Anemia Therapy
Definition
increase Hb level:
improve RBC O2 carrying capacity,
alleviate symptoms,
prevent anemia complications
Term
iron
Definition
vital nutrient in development of functioning erythrocytes;
essential for formation of hemoglobin
Term
Groups at high risk for Iron Deficiency Anemia
Definition
children <2 yrs old;
adolescent girls;
pregnant females;
elderly >65 yrs old
Term
Etiology of IDA
Definition
inadequate iron intake (dietary deficiency);
when demand > intake (blood donations, endurance sports, menstruation, pregnancy & lactation, infancy & adolescence [growth spurts]);
active bleeding/large blood loss;
inadequate absorption (drug or food interactions, gastrectomy, malabsorptive states);
impaired utilization;
Term
Recommended Daily Allowances of of Iron
Definition
Males: 8 mg;
Postmenopausal Females: 8 mg;
Menstruating Females: 18 mg;
Children & Pregnant Women require higher amounts: 30 mg/day for primary prevention of IDA;
Term
Iron Absorption
Definition
Best absorbed in Fe2+ (ferrous) form;
Fe3+ is ionized in stomach acid, then reduced to Fe2+ form --> 10-20% absorbed in duodenum & jejunem via intestinal mucosal cell uptake
Term
12-15 mg/day
Definition
amount of iron found in a normal western diet
Term
Early Lab Changes in IDA
Definition
decreased serum Fe;
decreased serum ferritin;
decreased TSAT%;
INCREASED TIBC
Term
Late Lab Findings in IDA
Definition
decreased Hb;
decreased Hct;
peripheral smear: microcytosis, hypochromia
Term
Signs & Symptoms of IDA
Definition
appear when Hb < 9 g/dL:
General symptoms - HA, cardiovascular, SOB;
glossitis (smooth, sore tongue);
reduced salivary flow;
pica (compulsive eating of nonfood items);
pagophagia (compulsive eating of ice);
koilonychia (spoon shape form to fingernails);
GI - nausea, anorexia, constipation
Term
Treatment of IDA
Definition
Treat underlying causes - severity & cause determines approach;
Replenish Fe stores;
Initial Tx:
1) dietary supplementation w/ iron-rich foods;
2) administer oral Fe therapy - 200 mg elemental Fe daily;
3) Parenteral therapy if indicated
Term
200 mg elemental iron daily in 2-3 divided doses (maximize tolerability)
Definition
recommended oral iron dose for pts with IDA;
depends on pt's ability to tolerate iron preparations;
tolerance improves w/ small initial dose & gradual escalation to full dose;
Term
Recommendations for pts who cannot tolerate recommended oral iron dose (200 mg)
Definition
smaller amounts are usually sufficient to replace stores but at a slower rate;
take at bedtime;
try a different formulation;
take with food --> decreases absorption by 50% but decreases GI side effects
Term
sodium ferric gluconate (Ferrlecit)
Definition
Ferrlicit;
NO Black Box Warning;
NO test dose required;
ADRs: cramps, nausea, vomiting, flushing, hypotension, rash, pruritus, upper gastric pain
Term
iron dextran (InFeD, DexFerrum)
Definition
InFeD, DexFerrum;
For pts w/ DOCUMENTED Fe DEFICIENCY;
Black Box Warning: anaphylactic-type rxns - Test dose required;
ADRs: pain & brown staining at injection site, flushing, hypotension, fever, chills, myalgia, anaphylaxis;
Equation used to determine amt needed:
Dose (mL) = 0.0442 (Desired Hb-Observed Hb) x IBW + (0.26xIBW)
Term
iron sucrose (Venofer)
Definition
Venofer;
NO test dose required;
Black-Box Warning: anaphylactic-type rxns;
ADRs: leg cramps, hypotension
Term
Furomoxytol (Faraheme)
Definition
Faraheme;
NO test dose required;
For pts with IDA AND CKD;
ADRs: hypotension, dizziness, constipation, nausea, peripheral edema
Term
epoetin (Epogen, Procrit)
Definition
1st line therapy for Anemia of CKD after ruling out other deficiencies;
Starting Dose:
SC - 80-120 units/kg/wk divided 2-3x/wk
IV - 120-180 units/kg/wk divided 2-3x/wk
Half-life = 27 hrs
Term
darbapoetin (Aranesp)
Definition
1st line therapy for Anemia of CKD after ruling out other deficiencies;
INCREASED duration of action;
ADV: less frequent dosing;
DISADV: longer time period to see effect;
Dosing:
Starting - 0.45 mcg/kg SC OR IV once weekly;
Half-life = 43 hrs --> less frequent dosing, weekly OR every other week;
Beneficial in pts in nondialysis CKD & pts who receive peritoneal dialysis;
Term
Equation used to determine appropriate dose of parenteral iron (Iron Dextran) in pts w/ IDA or anemia 2ndary to blood loss
Definition
Dose (mL) = 0.0442 (Desired Hb-Observed Hb) x IBW + (0.26xIBW)
Where Hb is 12 g/dL and dose is in mL, so must multiply by 50mg/mL of iron dextran to obtain mg dose.
Remember: iron dextran supplied as 50mg/mL
Term
oral iron products
Definition
ferrous sulfate, ferrous gluconate, ferrous fumarate, polysaccharide iron complex, carbonyl iron
Term
ferrous sulfate
Definition
20% elemental percentage;
elemental amount provided: 60-65 mg per 324-325 mg tablet;
formulation of choice for treatment of IDA b/c of tolerability, effectiveness, & low cost
Term
Adverse Rxns to Oral Iron Products
Definition
GI - dark discoloration of feces, CONSTIPATION, abdominal cramping, N/V;
-dose related;
Term
Response to Oral & Parenteral Iron Therapy
Definition
should be seen in 7-10 days;
Hb should rise 2-4 g/dL q3 weeks;
Reassess if Hb DOES NOT increase by 2 g/dL in 3 wks;
Administer 1 hr before or 2 hrs after meals;
Addition of ascorbic acid (vitamin C) 500-1000mg may INCREASE Fe absorption by 10% but if taken on empty stomach--> more GI side effects
Term
Drugs that Decrease Oral Fe Absorption
Definition
Al-, Mg2+, and Ca2+-containing antacids;
tetracycline, doxycycline;
H2-antagonists;
PPIs;
Cholestyramine;
caffeine
Term
Drugs Affected by Oral Iron
Definition
decreased L-dopa;
decreased methyldopa;
decreased levothyroxine;
decreased penicillamine;
decreased fluoroquinolones;
decreased tetracycline & doxycycline;
decreased mycophenolate
Term
Counseling Pts for Oral Iron Therapy
Definition
Keep out of reach of children;
Take on an empty stomach - at least 1 hr before meals;
Take 2 hrs before or after antacids, PPIs, and H2-antagonists, Ca supplements, fluoroquinolones, & tetracyclines;
Combine with stool softener or laxative to prevent constipation;
Liquid preparations --> teeth discoloration, can mix w/ fruit juice or milk, drink with straw;
Term
Common causes of Tx Failure in pts taking Oral Fe Therapy
Definition
poor pt adherence;
inability to absorb Fe;
incorrect diagnosis;
continued bleeding;
concurrent condition that impairs full reticulocyte response
Term
3-6 months
Definition
amount of time oral treatment for IDA should be continued after anemia is resolved --> allows for repletion of Fe stores to prevent relapse
Term
Indications for Parenteral Fe Therapy
Definition
evidence of iron malabsorption;
intolerance to oral administration;
Long-term nonadherence suspected;
pts w/ significant blood loss who refuse transfusions;
Term
NO, parenteral does not provide a quicker hematological response than oral Fe therapy
Definition
Does parenteral iron lead to a quicker hematological response than oral iron?
Term
vitamin B12 deficiency anemia
Definition
before treating folic acid deficiency anemia, this anemia MUST be ruled out
Term
Etiology of Vitamin B12 Deficiency Anemia
Definition
inadequate intake (RARE) - diet is only source;
decreased absorption - pernicious anemia (lack of intrinsic factor 2ndary to immune destruction of gastric mucosa);
inadequate utilization - transcobalamin II deficiency, renal glomerular dx, liver dx;
HYPERutilization - hyperthyroidism, pregnancy;
Term
Physical Findings of Vitamin B12 Deficiency Anemia
Definition
glossitis;
dysphagia;
anorexia/weight loss;
beefy red tongues;
Term
Neurologic Findings of Vitamin B12 Deficiency Anemia
Definition
numbness;
paresthesias;
peripheral neuropathy;
ataxia;
diminished vibratory sense;
increased deep tendon reflexes;
decreased proprioception;
imbalance
Term
Psychiatric Findings of Vitamin B12 Deficiency Anemia
Definition
irritability;
personality changes;
memory impairment;
dementia;
depression;
psychosis (rare)
Term
Lab Value Findings for Vitamin B12 Deficiency Anemia
Definition
decreased Hct;
INCREASED MCV;
INCREASED MCH;
decreased reticulocyte count;
decreased Vit. B12 level;
INCREASED iron & TSAT%
Term
Peripheral Blood Smear for Vitamin B12 Deficiency Anemia
Definition
macrocytosis;
hypersegmented polymorphonuclear leukocytes;
oval macrocytes;
anisocytosis;
poikilocytosis;
Term
Goals of Tx for Vit. B12 Def. Anemia
Definition
reversal of hematologic manifestations;
replacement of body stores;
prevention or resolution of neurological manifestations;
Term
Oral cyanacobalamin
Definition
Take 1-2 mg PO daily x 1-2 wks then 1 mg daily;
As effective as IM therapy in achieving hematological & neurological response;
AVOID time-released preps;
OTC is available;
Term
Parenteral cyanocobalamin (IM)
Definition
Initial: 1000 mcg/day x 2 wks, then 1000 mcg/wk until Hb WNL;
Maintenance: 1000 mcg/month;
Preferred route for pts exhibiting neurological symptoms;
Term
Intranasal gell cyanacobalamin
Definition
Inhale 500 mcg/wk (1 spray/wk);
AVOID in pts receiving meds intranasally in same nostril;
AVOID administering 1 hr before or after ingestion of hot foods or beverages;
ADV: pts who are homebound, have cognitive impairment, or dysphagia;
DISADV: efficacy not well studied, ONLY USED FOR MAINTENANCE therapy;
Term
Adverse Events from Cyanacobalamin (RARE)
Definition
RARE - hyperuricemia, hypokalemia, injection site pain, pruritus, rash, diarrhea;
Term
Monitoring Parameters for Tx w/ cyanacobalamin for Vit. B12 Deficiency Anemia
Definition
1) neurologic symptoms - improvement in 24 hrs, may not completely resolve;
2) CBC improvement - Hb & Hct normalize within 6-8 wks, reticulocyte count INCREASES within 3-4 days, Check CBC every 3-6 months
Term
Etiology of Folic Acid Deficiency Anemia
Definition
1) inadequate intake - poor eating habits (elderly, teenagers, alcoholics, food faddists, low socioeconomic class);
2) malabsorptive syndromes;
3) medication use (drugs that directly inhibit DNA synthesis [azathioprine, 6-mercaptopurine, 5-fluorouracil, hydroxyurea, zidovudine] & drugs that are folate antagonists - methotrexate, pentamidine, trimethoprim, primidone);
4) inadequate utilization;
5) hyperutilization - pregnancy, chronic inflammatory dxs, long-term dialysis, burn pts, growth spurts;
Term
Lab Value Changes in Folic Acid Deficiency Anemia
Definition
decreased Hct;
INCREASED MCV;
INCREASED MCH;
decreased reticulocyte count;
DECREASED folic acid level;
DECREASED erythrocyte folic acid level;
increased serum iron & TSAT%;
Term
Goals for Treatment of Folic Acid Deficiency Anemia
Definition
induce hematologic remission;
replace body stores;
resolve signs & symptoms;
treat underlying disorder;
increase dietary intake;
Term
Replacement Dosing for Folic Acid Deficiency Anemia
Definition
1 mg daily x 4 months;
may continue if risk factors for deficiency are still present;
Term
Maintenance Dosing for Folic Acid Deficiency Anemia
Definition
0.1-0.4 mg daily - up to 0.8 mg for pregnant/lactating women (initial prevention: 0.4 mg/day)
Term
Adverse Effects of Folic Acid Supplementation
Definition
bitter/bad taste;
GI upset - nausea, flatulence, anorexia;
nontoxic at high doses --> rapidly excreted in urine
Term
Monitoring Parameters for Treatment of Folic Acid Deficiency Anemia
Definition
CBC - MCV initially increases because of increases in reticulocytes
Term
Anemia of Chronic Dx
Definition
a common form found particularly in elderly; results from:
Chronic inflammation - TB, HIV, bacterial endocarditis, osteomyelitis, chronic UTIs;
Chronic Inflammation - RA, SLE, IBD, IOA, gout, etc.;
Malignancies - carcinoma, lymphoma, leukemia, multiple myeloma
Term
Lab Values for Anemia w/ Chronic Dx
Definition
decreased iron;
decreased or WNL transferrin;
decreased TSAT%;
INCREASED or WNL serum ferritin;
WNL soluble transferrin receptor;
DECREASED or WNL TIBC;
Term
Treatment Goals for Anemia of Chronic Dx
Definition
Aimed at underlying pathology;
RBC transfusions reserved for Hb <8-10 g/dL;
Use erythropoeitin and iron supplementation in proper pts;
Term
Indications for Erythropoeitin Use in pts w/ Anemia of Chronic Dx
Definition
cancer receiving chemotherapy;
chronic kidney dx;
HIV pts receiving myelosuppressive therapy
Term
Indications for Iron Supplementation in pts w/ Anemia of Chronic Dx
Definition
iron deficiency;
pts receiving erythropoietic agents
Term
Anemia of Chronic Kidney Dx
Definition
common form of anemia in these pts;
normocytic, normochromic anemia;
Factors responsible:
DECREASED ERYTHROPOIETIN PRODUCTION, shorter life span of RBCs, blood loss during dialysis, Fe deficiency, ACD, renal osteodystrophy
Term
Initiate in pts w/ Stage III CKD or higher: GFR <60 ml/min, Hb conc. <11 g/dL
Definition
When should one start anemia evaluation & treatment for pts with chronic kidney disease?
Term
Target Hb Level for Pts w/ Anemia of CKD
Definition
Hb >11-12 g/dL - NOTHING HIGHER THAN 12 g/dL!!!;
Hb >12 --> INCREASED cardiovascular events
Term
Adverse Events with Erythropoeitin agents
Definition
HYPERTENSION (most common);
seizures, thrombotic events, allergic rxns
Term
Monitoring of Outcomes for Erythropoiesis Stimulating Agents - epoietin, darbapoietin
Definition
Hb monitored every 1-2 wk, then every 2-4 wks when stable;
DO NOT change dose upwards more than every 4 wks;
Make adjustments in 25% intervals based on Hb levels;
Target Hb levels: 11-12 g/dL;
Withhold therapy if Hb >12 g/dL;
Pts who do not respond to therapy after 8 wks of optimal dosage should D/C
Term
Common Causes of Indequate Response to ESA Therapy
Definition
IRON DEFICIENCY (most common), infection/inflammation, chronic blood loss, osteitis fibrosa, aluminum toxicity, hemoglobinemias, folate or B12 deficiency, multiple myeloma, malnutrition, hemolysis, vit. C deficiency hypothyroidism
Term
Provide Iron Supplementation in Pts w/ Anemia of CKD
Definition
check baseline iron before & during ESA treatment;
Most pts REQUIRE supplemental therapy;
Maintain Stores at:
TSAT >20%, serum ferritin >100 ng/mL (pts NOT receiving hemodialysis), serum ferritin >200 ng/mL (hemodialysis pts);

if BELOW goal indices --> recommend supplementation
Term
IV Iron therapy recommended
Definition
For pts with Anemia of CKD, use this form of iron therapy
Term
Indications for Oral Iron Therapy
Definition
Pts w/ Anemia of CKD who DO NOT have IV access:
Pts w/ Stage III & IV CKD,
receiving peritoneal dialysis,
switch to IV if unable to manage
Term
Evaluation of Therapeutic Outcomes w/ Iron Therapy
Definition
for pts receiving ESA therapy, monitor Fe stores:
monthly in pts NOT receiving iron supplements,
EVEY 3 MONTHS in pts WHO ARE receiving Fe supplements;
When goal Hb is met (11-12 g/dL), monitor stores EVERY 3 MONTHS
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