Iron Deficiency Anaemia

Introduction

Iron deficiency anaemia is the most common cause of anaemia worldwide, accounting for approximately 50% of all cases.

  • It is diagnosed when iron deficiency is accompanied by anaemia.

Diagnostic lab findings:

  • Complete blood count: Low red blood cell count (RBC), haemologbin (Hb), haematocrit (Hct) and mean corpuscular volume (MCV).
  • Serum ferritin: <30 ng/ml (the threshold is typically higher in patients with chronic inflammatory state).
  • Iron panel: Decreased serum iron and increased TIBC (total iron binding capacity) resulting in a lower transferrin saturation.

NOTE: Transferrin saturation (TSAT) is the ratio of serum iron to TIBC: (serum iron ÷ TIBC x 100). If not provided directly by a lab, it can be calculated manually. Normal values range from 25 to 45%.



Dietary Iron

Dietary iron exists in two primary forms:

  • Heme iron - found in meat, poultry and seafood
  • Non-heme iron - found in nuts, beans, vegetables and fortified grains, such as cereals.

Heme iron is more readily absorbed than non-heme iron, which is affected by gastric pH and other foods being consumed, but both sources are important.

  • Meat, seafood, poultry and ascorbic acid increase the absorption of non-heme iron, while foods that contain phytate and polyphenols (e.g. grains, beans, cereals and legumes) can decrease non-heme iron absorption.
  • This is particularly important for patients who follow a vegetarian diet, since they are more likely to consume foods with a less absorbable form of iron along with foods that decrease the absorption of iron.
  • Vegetarians may require iron supplementation, even if dietary intake of iron seems adequate.

Factors Influencing the Absorption and Bioavailability of Dietary Iron



Causes

  • Inadequate dietary intake
  • Increased need for iron (e.g. pregnancy, lactation, rapid growth during adolescence).
  • Decreased iron absorption (e.g. elevated gastric pH, celiac disease, gastric bypass)
  • Bleeding (e.g. traumatic haemorrhage, heavy menstrual bleeding, GI haemorrhage, frequent blood donation)



Management

Eating a diet higher in bioavailable iron can help manage iron deficiency but dietary changes alone are rarely sufficient to replenish depleted iron stores.

  • Iron-rich foods include red meat, poultry, fish, beans, dark green vegetables, raisins, apricots, prunes, and iron-fortified breads and cereals.

Oral iron supplementation can adequately treat most patients with iron deficiency anaemia.

  • Evidence suggests that alternate-day dosing (taking the iron every other day rather than every day) results in equivalent or better iron absorption than daily dosing, usually with fewer gastrointestinal side effects.
  • Take oral iron on an empty stomach.
    • If stomach upset occurs, it can be taken with food, but avoid cereals, tea, coffee, eggs, milk and high fibre products, as these decrease iron absorption.
    • Iron polymaltose is absorbed best if taken during or immediately after a meal.
  • Co-administering vitamin C provides an acidic environment that theoretically increases iron absorption.
    • However, recent evidence suggests this benefit is likely clinically insignificant, and it is associated with a higher rate of GI upset.
  • Take oral iron 2 hours before or 4 hours after taking antacids.
    • H2 antagonists and proton pump inhibitors raise gastric pH for up to 24 hours; separating the administration of these agents from iron supplements does not improve absorption.
  • Dark stools are an expected, harmless side effect. If you develop constipation, your healthcare provider can recommend a stool softener (e.g. docusate sodium).
  • Switching to a formulation with a lower amount of elemental iron may also improve tolerability of oral iron.

Parenteral iron therapy is typically reserved for select patient populations due to a higher risk of side effects, cost and administration burden.

  • Indications
    • Intolerance/nonadherence to oral therapy
    • Chronic bleeding not manageable with oral iron
    • Anatomic or physiologic conditions that interfere with oral iron absorption (e.g. inflammatory bowel disease, bariatric surgery)
    • Severe iron deficiency anaemia (Hb <8 g/dL)
    • Need for rapid recovery; although the initial rise in Hb is more rapid with IV iron compared with oral iron, Hb increase at 12 weeks reported to be similar between the 2 routes.
    • In patients taking erythropoiesis-stimulating agents (ESA), for example, those with anaemia of chronic kidney disease
  • Administration of IV iron reduce the use of blood transfusion, which in turn avoids transfusion-associated risks.
  • All parenteral iron products carry a risk of hypersensitivity reactions (including anaphylaxis), while ferric carboxymaltose carries a higher risk of persistent hypophosphatemia and osteomalacia compared to other IV formulations.

NOTE: IV iron is contraindicated in the first trimester of pregnancy.

Patients with severe, severely symptomatic, or life-threatening anaemia should be treated with red blood cell (RBC) transfusion because correction of iron deficiency anaemia using iron replacement requires time for iron administration and incorporation into RBCs.



Follow-Up

Patients on oral iron therapy

  • Initially, low hepcidin levels in patients with iron deficiency anaemia promote iron absorption resulting in rapid recovery of haemoglobin levels
    • Reticulocyte count typically starts rising by 4 days after initiation of treatment and reaches maximum at 7-10 days
    • Haemoglobin concentration typically increases by second week of therapy
  • Optimise response to oral iron is usually defined as Hb increase of 2 g/dL after 3 weeks.
  • Oral iron should be continued for 3-6 months after anaemia has been corrected in order to replenish iron stores (serum ferritin >50-100 mcg/L).

Patients on IV iron supplementation

  • Ferritin should be checked every 3-4 months, and if it falls to <50 mcg/L, iron infusions should be repeated.
  • Patients with continued gastrointestinal bleeding should have ferritin level checked more often and may require frequent infusions.



Summary

Treatment of iron deficiency and iron deficiency anemia involves more than simply replacing iron.

  • In all patients, the cause of iron deficiency must be identified and directly addressed.



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