Principles of Therapy
Iron-deficiency anemia caused by an underlying condition should be treated or referred to a subspecialist for further workup and definite treatment. Patients with iron-deficiency anemia have good response from iron replacement therapy.
Pharmacological therapy
Iron Therapy (Oral)
Oral administration is the preferred route of iron therapy and is the
first-line treatment in patients with uncomplicated iron deficiency. Oral
formulations include iron (II) salts (eg Ferrous sulfate, Ferrous gluconate, Ferrous
fumarate, Ferrous, bisglycinate, Sodium ferrous citrate), Iron (III)
polymaltose complex, Ferric pyrophosphate, Iron protein succinylate, and
liposomal iron. It must be noted that there is no oral iron formulation that
shows clear clinical advantage over others. Oral ferrous iron is readily
absorbed due to its higher solubility while ferric iron has longer period of
active absorption, but both have been effective in correction of
iron-deficiency anemia. Carbonyl iron consists of microparticles of elemental iron;
thus, it is not an iron salt, however, it is also used for iron-deficiency
anemia. Its efficacy and side effect profile are comparable to other oral iron
formulations. Oral iron is taken once daily at most. The dosage of elemental
iron required to treat iron-deficiency anemia in adults is 100-200 mg/day for 3
months. Pregnant women should take 60-120 mg /day
of elemental iron until hemoglobin is ≥11 g/dL, then reduce to a prophylactic dose of 30-60
mg/day for 3 months or 6 weeks postpartum, whichever is longer, to restore iron
stores.
Please see Nutrition in Pregnancy
disease management chart for further information.
The recommended doses for children are 3-6
mg/kg/day of elemental iron in liquid preparation for 3-4 months. The GI
adverse effects such as epigastric discomfort, nausea, diarrhea, metallic
taste, thick green stools, and mild to severe constipation (usually in pregnant
women) may cause non-compliance to therapy. It must be noted that these GI
effects are usually seen in ferrous iron forms and can be minimized by taking
the oral iron supplement after meals although it may cause decreased
absorption. Such adverse effects may also be reduced by reducing doses or by alternate-day
dosing. Ferric iron and slow-release ferrous salts and Iron (III) polymaltose
complex have reduced GI disturbances thus having better tolerance rate.
Liposomal iron, a ferric pyrophosphate preparation associated with ascorbic
acid and carried within a phospholipid membrane, has a low incidence of side
effects and high bioavailability. Other oral therapies with improved absorption
and lesser GI side effects include Ferric maltol, sucrosomial iron, Iron
hydroxide adipate tartrate and Ferric citrate. Enteric-coated preparations may
also improve tolerability but reduce absorption.
Iron absorption is enhanced in a mildly acidic medium; thus, iron salts
should be taken on an empty stomach or Ascorbic acid (either by tablet or half
glass orange juice) may be added. Ascorbic acid,
retinol, and carotenes can overcome the negative effect on iron absorption
of all inhibitors, including phytate, polyphenols, the
calcium and proteins in milk products, tea, coffee, red wine, soy protein and
egg, and it will increase the absorption of both native and fortified
iron. Oral iron formulations which should be taken with meals include heme iron
polypeptide, polysaccharide iron complex, and Ferric citrate. Intake of PPIs
and those that induce gastric acid hyposecretion can reduce iron absorption.
Once adequate response to treatment after a month has been established (increase
in hemoglobin of 1 g/dL within 2 weeks or level within normal range), therapy
should be continued for 3-6 months for iron stores to be replenished (ferritin
>100 ng/mL). Switch to a low-dose oral iron for maintenance once
iron-deficiency anemia has resolved. Only iron salts are recommended in women
during the first trimester of pregnancy. Oral therapy combinations of iron,
folic acid, vitamin B12, and vitamin C are administered easier in women than
the single component oral iron preparations. Multiple
micronutrient supplements containing iron and folic acid are preferred over
iron and folic acid alone for pregnant women, but those with >30 mg of iron
are not recommended due to side effects.
Iron Therapy (Parenteral)
Iron dextran, Iron sorbitol, Iron sucrose,
Ferric caboxymaltose, Ferric derisomaltose, Ferumoxytol, and Sodium ferric
gluconate are the most common parenteral forms of iron therapy. Parenteral iron
therapy is indicated in patients with moderate to severe iron-deficiency anemia, who cannot tolerate or absorb oral
preparations (eg previous gastric surgery, bariatric procedures), those with
inadequate response to appropriate oral therapy, who did not tolerate trial
therapy with two different oral iron agents, poor compliance with oral iron, with hemoglobin levels continuing
to fall, worsening symptoms of inflammatory bowel disease (IBD), unresolved
bleeding, chronic heart failure, and chronic kidney disease (CKD) or renal
failure-induced anemia treated with Erythropoietin, and women in the second or
third trimester of pregnancy. In patients with IBD, active inflammation should
be treated to enhance iron absorption or reduce iron loss from GI bleeding.
Intravenous (IV) iron therapy is also
indicated if the condition requires a rapid increase in hemoglobin level (eg
prior to a major surgery if interval between diagnosis or iron-deficiency
anemia and surgery is too short for oral iron to be effective) or the amount of
blood loss or iron to be replenished exceeds the capacity of the GI tract to
absorb oral iron preparations. IV iron therapy is preferred in hemodialysis
patients. A “total-dose” infusion (where iron stores are repleted in a single
treatment episode) can be given; IV iron formulations allowing correction of
iron deficiency in 1-2 infusions are preferred over those needing multiple
infusions. However, it must be noted that IV iron therapy has a risk of serious
allergic reactions, majority of which are complement activation-related
pseudo-allergy, which should be treated accordingly. Studies have shown
that there are higher risks with high-molecular-weight iron dextran than with
low-molecular-weight iron dextran and non-dextran forms (eg Iron sucrose,
Sodium ferric gluconate). Underuse of IV iron may have stemmed in part from
concerns about the risk of serious allergic reactions. Intramuscular (IM)
injection of iron discouraged due to associated pain, permanent skin staining,
variable absorption, and not being safer than IV infusion.
Nonpharmacological
Dietary
Therapy
To aid in supplemental doses of iron and for secondary prevention of
iron deficiency, an increase in dietary iron intake is recommended. Diet rich
in iron are red meat, chicken, fish, legumes, and green leafy vegetables. Cow’s
milk consumption is limited to 500 mL/day. Iron-fortified
milk formula may be used in preventing iron deficiency in infants. Inhibitors
of iron absorption (eg calcium, tannins in coffee and tea, milk and dairy products, phytates in cereals, quinolone and
tetracycline antibiotics) should be decreased or removed from meals rich in
iron. Lasty, adherence to a gluten-free diet
improves iron absorption in patients with celiac disease.
Blood
Transfusion
Transfusion with packed RBCs is only reserved for severely symptomatic
patients with cardiovascular (CV) complications. The target hemoglobin is 7-8
g/dL; transfusion should be followed with iron replacement therapy. Blood
transfusion is indicated in patients who are unstable hemodynamically due to
active bleeding or at risk of further bleeding, pregnant
women with hemoglobin levels of <6 g/dL or
severe anemia especially as the delivery date approaches, and/or those
who show evidence of end-organ ischemia. It is essential to assess the
patient’s clinical condition and symptoms in deciding whether blood transfusion
is needed.
Anemia - Iron-Deficiency_Management