Anemia - Iron-Deficiency Management

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. 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 have 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. Studies have shown that ascorbic acid can overcome the negative effect on iron absorption of all inhibitors, including phytate, polyphenols and the calcium and proteins in milk products, 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. 

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 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, 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, pregnant women with hemoglobin levels <6 g/dL, 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