Therapeutic Discussion – Anemia
Basic Pathophysiology
 Decrease in either Hgb or RBCs = reduced O2 carrying capacity
 Causes = decreased RBC production (CKD, bone marrow malignancy, Fe/B12/folate deficiencies); increased RBC destruction
(intravascular hemolysis; extravascular hemolysis – abnormal lab values: decreased haptoglobin b/c bound to Hgb so free is low,
bilirubin increased = jaundiced, scleralicterus, dark urine, increased LDH – found in RBC; Coombs test (DAT) – measures if
autoimmune and therefore can treat with CCS); increased blood loss
 RBCs formed in marrow & EPO (produced by kidneys) stimulates growth; Hb & Fe are incorporated into the gradually maturing
RBC which is released into the blood stream as a reticulocyte  loses nucleus = erythrocyte (120 day survival time)
 EPO prevents apoptosis of precursor cells; production stimulated by a decrease in [tissue O 2]
 Transferrin transports iron to marrow for incorporation into Hgb
 ACD – blunted EPO response to anemia, disturbance of Fe homeostasis
 Affinity of Hgb for O2 influenced by: decreasing pH, CO2, 2,3-bisphosphoglycerate & increased temp = Hgb releases O2
 Body produces ~6.25 g of Hgb daily
 Normal iron content = 3-4 g (2.5 g exists as Hgb; 3-7 mg bound to transferrin; rest as storage in form of ferritin)
 Heme iron (meat, fish) is 3x more absorbable than nonheme iron (veggies, fruits, nuts, grains, dietary supplements)
 What are the types of anemia?
o Macrocytic = Vitamin B12/Folic acid deficiency anemia (abnormal DNA metabolism) turn off for growth is b12/folate
o Microcytic hypochromic = Fe deficiency; thalassemia (dx in younger pts) (quantitative deficiency in Hb synthesis)
 Prelatent: reduction in Fe stores w/o reduction in serum Fe levels – assessed w/ serum ferritin
 Latent: iron stores depleted, but Hgb is above lower limit of normal – reduced transferrin sat & increased TIBC
 IDA: Hgb less than normal
o Normocytic = anemia of chronic diseases (due to inflammation); blood loss; hemolysis
CC, HPI,
Subjective
findings
PMHx
Meds
PTA
Social Hx
Objective
 What are the symptoms of anemia?
Mild – asymptomatic
Vitamin B12 deficiency – neurologic Sx (numbness, paresthesias, peripheral neuropathy, ataxia, imbalance)
Decreased exercise tolerance; fatigue; dizziness; irritability; weakness; palpitations; vertigo; SOB; chest pain
IDA – 50% have GIB cause
 What are the risk factors?
Vitamin B12 – inadequate intake, malabsorption syndromes, inadequate utilization; B12 – pernicious anemia, absence
of intrinsic factor
Folic acid – inadequate intake, decreased absorption, hyperutilization (pregnancy, hemolytic anemia, malignancy,
chronic inflammation D/O), inadequate utilization; alcohol (affects absorption)
 Are there any medications that may cause anemia?
Macrocytic – hydroxyurea, MTX, AZA, 6-MT
 What are lifestyle risk factors for anemia?
Poor diet, alcoholism
 How do we diagnose anemia?
See labs below
Vitals: increased HR; hypoT
Vitals
CNS: decreased mental acuity; lightheadedness; fatigue/weakness; faintness
Physical Exam
HEENT: headache
CVS: increased murmurs; palpitations; angina; go into HF
Resp: breathlessness
MSK/Derm: pale appearance; sensitivity to cold
Investigations Lab IDA: L serum iron; L ferritin levels; H TIBC (>400 mcg/dL; if <200 = inflammatory disease);
increased RDW (nonspecific)
Macrocytic: increased/normal MCV; mild leukopenia/thrombocytopenia; L retic; L Hct; Vit
B12 of 200-300 pg/mL
ACD: L Fe; L/N transferrin; H/N ferritin; L TIBC; L T sat
Hgb < 130/120 (M/F); Hct decreased; RBC decreased
EKG:
Dx
Echo:
Goals of therapy
IDA – replenishing iron stores
Vitamin B12 – reversal of hematologic manifestation, replacement of body stores, px/resolution of neurologic manifestations
ACD – treat underlying D/O, correct reversible causes
Treatment alternatives and duration
IDA: Goal = 150-200 mg elemental Fe/day x 3-6 months after anemia restored
o
Gluconate = 35mg; green
o
Sulfate = 60mg; red
All come as 300 mg tabs
o
Fumarate = 100mg; purple
Parenteral iron (doesn’t lead to quicker hematologic response than PO iron) reserve for CKD pts on HD
o Iron dextran  anaphylaxis leading to death – need test dose; least safe; IV > IM (50mg iron/mL – max 2mL/site)
o Processed by macrophages for iron to be biologically available
o Slowly absorbed over months (60% after 3 days; 90% w/in 3 weeks)
o Diluted in 250-1000 mL NS/D5W & infused over 4-6 hours
o Sodium ferric gluconate (62.5mg/5mL)  less anaphylaxis – no test dose needed
o Hemodialysis patients require 1g over 8 sessions
o Administered as 10 mL (125 mg Fe) in 100 mL NS over 1 hour
o Iron sucrose (20mg/mL)
o Hemodialysis: 100mg IV 1-3x/week (total 1000mg in 10 doses)
o Dilute in NS (100mL) & infuse over 15 min
Blood transfusions if Hgb <70 g/L or <90 g/L if CV history  should increase Hgb by 10
Vitamin B12 1-2mg PO/IM daily; 1000mcg cyanocobalamin x 1 week, then weekly x 1 month, then monthly therafter – can switch to
1 mg PO daily (parenteral if neurologic Sx)
Folic acid 1mg daily; malabsorption = 1-5 mg daily; x 4 months if underlying cause identified and corrected; 400mcg pregnant
ACD: RBC transfusions; EPO (darbepoetin alfa longer t1/2 than epoetin alfa) – most evidence in CKD (target Hgb of 110); NOT in
cancer pts (increases risk of thrombosis, cancer tx failure, death); DM pts with CKD not on HD – increases risk of stroke via
increasing viscosity of blood; also used in Jehovah Witness; Fe only if unresponsive to EPO; NO Fe if ferritin >100
Monitoring Parameters: Efficacy and toxicity
Efficacy:
Fe PO: increase retics in 3-5 days (if not seen, something may be wrong in bone marrow); increase Hgb 2-4 g/dL Q3weeks (if not,
may not be receiving enough Fe); ferritin will take 6 months to restore
Vitamin B12: retics 2-5 days & peak at 7 days; Hgb rises after 1st week; leukocyte/platelets normalize after ~7 days
Folic acid: retics 2-3 days & peaks w/in 5-8 days; Hct rises w/in 2 weeks and normal w/in 2 months
EPO: retics 2-3 days; iron status; Hgb ~4 weeks, then every 2-4 weeks thereafter (max 8 weeks if no response)
Safety:
Fe PO: stomach upset; constipation (dose-dependent)
Iron Dextran: arthralgias, myalgias, flushing, malaise, fever; staining of skin, inj site pain; allergic rxns
Na Ferric Gluconate: cramps, N/V, flushing, hypotension, intense upper gastric pain, rash, pruritus
Fe Sucrose: leg cramps, hypotension
Vitamin B12: hyperuricemia, hypoK, fluid retention
EPO: Fe deficiency; increased BP, nausea, H/A, fever, bone pain, fatigue; seizures, thrombotic events, allergic rxns, death/MI
Hct = actual volume of RBCs in unit volume of blood (~3x Hgb); low = reduction in either number/size of RBCs or increase in plasma
volume
MCV = average volume of RBCs
MCH = % volume of Hgb in RBC
MCHC = weight of Hb per vol. of cells; independent of cell size therefore low = hypochromia
RDW = higher means more variable size of RBCs
Serum Fe = conc. of Fe bound to transferrin
Iron
Folate
B12
Hct
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RBC
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HgB
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MCV
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MCHC
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RDW
/
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Ferritin
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TIBC
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Serum Fe (diurnal
-/
fluctuations)
% Transferrin
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Saturation
(0.2-0.5)
Ferritin is also an acute phase reactant, therefore increased in inflammation and infections
- If all labs fit IDA, except ferritin, use:
CD
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-/
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o Ferritin/3 < 20 = IDA; > 20 = inflammation/infection
Ferritin is also the most representative of iron deficiency extent (i.e. if ferritin low, Sr Fe has been used up and now stores are being
depleted)
T-Sat > 50%, worry about iron toxicity
Hgb levels of 80 g/L associated with a doubling of the odds of death
If giving blood to patient and Hgb not increasing  may be due to blood loss or they may be hemolysizing it
Fe absorbed in ileum (latter end of duodenum as well)