Anemia: Therapeutics 2 Flashcards
Iron Absorption
hepcidin role
Daily intake of iron in diet
is 10-20 mg
Absorb 1-2 mg iron/day
Lose 1-2 mg iron/day
through desquamation of
epithelia
Normal iron content of the
body is about 3-4 g
Hepcidin is regulator of intestinal iron absorption, recycling, and iron mobilization from hepatic stores
Clinical Signs and Symptoms of IDA
• General symptoms of anemia – fatigue, decreased exercise tolerance • Pallor may be more noticeable • Koilonychia (spooning of fingernails) • Pica – compulsive eating of nonfood items • Crave eating ice • Sore or smooth tongue
Iron Deficiency Anemia
LABS
– ↓ Serum Ferritin – diagnostic test of choice • < 15 ug/L – diagnostic of IDA • 15 – 50 ug/L – probably IDA • 50-100 ug/L – possible IDA • > 100 ug/L unlikely to be IDA
less than 50 is a good indicator of iron deficiency - dont need to memorize other numbers
• interpret ferritin with caution in presence of inflammation, liver or renal disease, or malignancy (there is grey area)
– Additional tests may be useful if hematology profile
suggests IDA but ferritin normal: ↓ serum iron, ↓
transferrin saturation (<15%),↑ TIBC (increased)
Dietary intake:
for mild anemia
<20g/L –> need supplements
– iron best absorbed from meat (heme) vs fruits, vegetables, dairy, grains (non-heme)
better absorbed from meat
– ascorbic acid increases the absorption of nonheme iron
– recommended dietary allowance for iron is 8 mg in adultmales and post-menopausal females and 18 mg in
menstruating females (children and pregnant women have increased iron demands)
– amount of iron absorbed from food depends on body
stores, rate of RBC production, type of iron in diet and
presence of substances that enhance or inhibit iron
absorption
Oral Iron supplement:
– ~ 100 mg elemental iron per day (maximum
absorption of iron in duodenum) (sometimes 200 but not often well tolerated by pts)
– Absorbed better on empty stomach but may take with food to decrease GI side effects
• Best to avoid with cereals, dietary fibre, tea, coffee, eggs, or milk
– Recent evidence suggest alternate day dosing of iron
(or twice weekly) can be used
• Daily of iron yield similar or slightly better Hgb (~3 g/L)
versus twice weekly or alternate day dosing over about 3 months
• Adverse events reduced up to 30% with intermittent dosing
– Adverse effects:
• GI upset, dark discoloration of feces, constipation or diarrhea (reason why ppl stop iit)
IDA Treatment – Clinical Pearls
there should not be blood loss postmenopausal
eg. celiac disease
• most oral iron salts have similar absorption – differ in
elemental iron content
• maximal absorption occurs in duodenum (acidic
medium)
– slow release or enteric coated preparations often not properly absorbed and therefore should be avoided
• dose (and formulation) depends on patient tolerability
– starting at a lower dose and increasing gradually over several days or taking supplements with food
– alternate day dosing may improve fraction absorbed (e.g., 65mg
- 200 mg every 2 days)
• important to determine and correct underlying
cause of iron deficiency (where possible)
Iron Formulations - Comparison
Ferrous fumarate (Palafer®) ~ 100 mg/ 300 mg tab
Ferrous gluconate ~35 mg /300 mg tab) - less harsh, tolerate better
- these 2 are cheap
Ferrous sulfate ~60 mg /300 mg tab)
Heme-iron polypeptide (Proferrin®) 11 mg heme iron/tab Polysaccharide-iron complex (FeraMAX®) 150 mg elemental /capsule
- very expensive compared to ferrous , not first line
Are there differences in oral iron
formulations?
• Polysaccharide-iron complex and heme iron are more
expensive
– May have advantages such as lack of metallic taste; evidence to support less adverse effects inconsistent
• Similar efficacy (Hgb level) with oral heme iron and ferrous sulfate in study of patients with chronic kidney disease that had IDA
• Ferrous sulfate slightly more effective than polysaccharideiron complex in young children
• In pregnancy, one study showed oral iron polymaltose
complex better tolerated than ferrous sulfate, however no serious side effects in either group
• Drug Interactions:
Decrease iron absorption:
• Al, Mg, Ca-containing antacids
• Tetracycline and doxycycline
• PPIs, and H2-blockers
– Drugs affected by iron:
• Levodopa, levothyroxine, fluoroquinolones,
tetracycline and doxycycline, mycophenolate,
bisphosphonates
- separate the iron from calcium from thyroid
time to assess deprescribing PPIs
Parenteral (IV or IM) iron:
– may be necessary if evidence of iron malabsorption,
intolerance of oral, or nonadherence
– Iron Dextran (complex of ferric hydroxide and dextran;
50 mg iron/mL)
• Consult prescribing information for dose calculation, dilution and administration details
• IV dose: should not exceed 50 mg of iron per minute
• AE: anaphylaxis, dyspnea, headache, flushing, hypotension, urticaria,
myalgia, arthralgia, staining of skin, pain at injection site
can stain skin
Monitoring:
– Oral:
• usually check CBC after 3-4 weeks - correction after 6-10 weeks
• Hgb typically increases by 10-20 g/L in 2-4 weeks while on
therapy
• continue until iron stores repleted – typically 3-6 months of
therapy – check ferritin before discontinuing
• once anemia corrected and iron stores normalized, low
maintenance dose may be considered if ongoing need
• monitor for adverse effects, adherence – most common cause
of treatment failure is poor adherence due to gastrointestinal
side effects
Laboratory Findings - IDA
RBC, Hgb, Hct ⇓ MCV ⇓ MCHC ⇓ Reticulocytes ⇒⇓ RDW ⇑ Serum iron ⇓ TIBC ⇑ Transferrin saturation ⇓ Ferritin ⇓
Etiology – Macrocytic Anemia
Vit B12 deficiency – Dietary deficiency – Deficiency of intrinsic factor • pernicious anemia, gastrectomy – Intestinal malabsorption (crohns), PPIs can affect B12 abs – Food-cobalamin malabsorption
• Folate deficiency
– Dietary (rare now to foods fortified with folic acid)
– Defective conversion to active form (e.g. methotrexate)
– Increased requirement (pregnancy)
– Intestinal malabsorption
Other causes of macrocytic anemia (nonmegaloblastic-no impairment of DNA synthesis) include liver disease, alcoholism, and hypothyroidism.
Drug-Induced Macrocytic Anemia
Marrow toxicity & interference with folate
metabolism
Alcohol
Marrow toxicity: Antineoplastics, zidovudine Altered folate metabolism Anticonvulsants, Methotrexate, Sulfasalazine, Sulfamethoxazole, Triamterene, Trimethoprim
**B12 malabsorption:
Metformin
Proton pump inhibitors
Signs & Symptoms - Macrocytic
As for general • GI symptoms – anorexia, intermittent constipation & diarrhea, abdominal pain • B12- neurological symptoms, beefy red tongue – Need to have high index of suspicion in the elderly
