Iron Deficiency Anemia in Adults

Background

• Iron deficiency anemia, which occurs when iron deficiency has progressed to iron-deficient erythropoiesis, is the most common cause of anemia worldwide, accounting for about 50% of cases.
• Anemia is defined by hemoglobin (Hb) levels according to the Centers for Disease Control and Prevention and World Health Organization.
  • For menstruating adults, Hb < 12 g/dL (120 g/L)
  • For pregnant adults, Hb < 11 g/dL (110 g/L)
  • For male adults Hb, < 13 g/dL (130 g/L)
• Causes of iron deficiency anemia:
  • Iron deficiency and iron deficiency anemia may occur due to increased need for iron (for example, during pregnancy), decreased iron intake (for example, lack of iron sources in the diet), decreased iron absorption (for example, Celiac disease) or loss of iron (for example, bleeding).
  • Menstrual blood loss is the most common cause of iron deficiency anemia in female adults premenopause, while blood loss from the gastrointestinal tract is most common cause in male adults and female adults postmenopause.
  • Iron deficiency anemia may be a predictor of asymptomatic colonic and gastric carcinoma, especially in male adults and female adults postmenopause.
  • In some patients, iron deficiency anemia may be multifactorial, or may coexist with other causes of anemia, especially anemia of inflammation
• Patients may be asymptomatic or present with signs and symptoms of:
  • iron deficiency, including pica, restless legs, atrophic gastritis, and angular cheilosis
  • anemia, including fatigue, shortness of breath, alopecia, and headache
  • underlying condition causing the anemia
• Food-based approaches or routine iron supplementation may be used in specific populations such as, pregnant adults, menstrurating adults, and vegetarians and vegans, to prevent iron deficiency anemia.

Evaluation

• Iron deficiency anemia is diagnosed when iron deficiency is accompanied by anemia (low Hb level).
• Suspect iron deficiency anemia in patients with:
  • signs and symptoms of iron deficiency, but iron deficiency may be asymptomatic and physical exam findings are not sensitive for anemia
  • microcytic and hypochromic anemia
• If iron deficiency anemia suspected, consider performing tests to assess iron status including:
  • serum ferritin
  • serum iron
  • total iron binding capacity (TIBC)
  • Diagnosis of iron deficiency is generally made based on serum ferritin levels below 15 mcg/L in the absence of inflammation) or below 100 mcg/L in the presence of inflammation (since ferritin is an acute phase reactant) and transferrin saturation (TSAT) below 16%-20%.
  • Recommended serum ferritin cutoffs and TSAT cutoffs to determine iron deficiency according to various organizations:

Table 1. Summary of Criteria Used to Diagnose Iron Deficiency in Different Patient Populations

• Diagnosis of iron deficiency may be supported by:
  • Decrease in mean corpuscular volume (< 80 fL)
  • Increase in total iron-binding capacity (> 68 mmol/L)
  • Increase in percentage of hypochromic red blood cells (HRC) (> 6%)
  • Decrease in reticulocyte Hb content (CHr) or Ret-Hb (< 29 pg)
• For patients with unexplained iron deficiency or iron deficiency anemia, consider tests to determine source of iron deficiency.
  • In all male adults and female adults postmenopause with iron deficiency anemia:
    • perform upper and lower gastrointestinal investigations (unless history of significant overt non gastrointestinal blood loss is present) (Strong recommendation)
    • consider testing for Helicobacter pylori infection in patients with recurrent iron deficiency anemia and normal esophagogastroduodenoscopy (OGD) and colonoscopy findings (Weak recommendation)
    • consider screening for celiac disease in all patients with iron deficiency anemia (Weak recommendation).
  • In females premenopause, consider:
    • gynecologic workup for excessive or irregular menstrual bleeding
    • pregnancy and thyroid-stimulating hormone (TSH) tests
• For diagnosis of iron deficiency anemia in specific patient populations see:
  • pregnant adults
  • patients with chronic kidney disease (CKD)
  • patients with inflammatory bowel disease (IBD)
  • patients with heart failure
  • other patient populations including patients with cancer and patients with iron refractory iron deficiency anemia
• Screening:
  • Consider screening nonpregnant adults of childbearing age for anemia
    • annually for female adults at high risk for iron deficiency including those with extensive menstrual or other blood loss, low iron intake, or previous diagnosis of iron deficiency anemia
    • every 5-10 years in all others
  • Screen all pregnant adults for anemia using blood count at booking and at 28 weeks (Strong recommendation).

Management

• Goals of treatment in iron deficiency anemia include identification and treatment of underlying cause, restoration of hemoglobin (Hb) concentrations and red cell indices to normal, and further evaluation in the absence of response.
• Treatment options for iron deficiency anemia include:
  • dietary measures - eating a diet higher in bioavailable iron can help treat iron deficiency but diet modification alone is unlikely to result in repletion of iron stores
  • administration of iron supplements, including oral and IV iron
• Use of oral versus IV iron:
  • Most clinical practice guidelines recommend oral route as first-line treatment for iron deficiency.
  • IV iron use has been suggested for severe iron deficiency anemia (Hb < 8 g/dL [80 g/L]) as first-line therapy, due to superior efficacy and rapidity in increasing Hb levels.
  • Other indications for using IV iron as initial treatment include iron deficient patients with:
    • clinically active inflammatory bowel disease
    • chronic kidney disease undergoing dialysis and receiving erythropoiesis-stimulating agents
    • heart failure
    • genetic iron refractory iron deficiency anemia
    • need for quick increase in iron levels such as after chronic blood loss
    • malabsorption
    • refractoriness to oral iron therapy
  • Choice of iron preparation and administration route also depends on administration factors (number of visits, length of administration episode), tolerability, safety and practicability, and cost of agent
• Additional treatment strategies maybe required for iron deficiency anemia in specific patient populations including:
  • pregnancy, postpartum period and in adults with heavy uterine bleeding
  • preoperative patients
  • patients with inflammatory bowel disease
  • patients with Helicobacter pylori infection
  • patients with cancer
  • patients with chronic kidney disease
  • patients with heart failure
  • in critically ill patients