From the Guidelines
For iron deficiency without anemia, I recommend starting with oral iron supplementation, such as ferrous sulfate 100-200 mg daily, and taking it on an empty stomach with vitamin C to enhance absorption, as suggested by the most recent guideline 1. The workup should include a thorough history focusing on potential causes like menstrual blood loss, pregnancy, dietary insufficiency, malabsorption, or occult bleeding.
- Laboratory evaluation should include:
- Complete blood count
- Ferritin
- Iron studies (serum iron, total iron binding capacity, transferrin saturation)
- Possibly testing for celiac disease or H. pylori if suspected Treatment should continue for 3-6 months to replenish iron stores, with follow-up ferritin levels checked after 3 months 1. For premenopausal women with heavy menstrual bleeding, no additional GI workup is typically needed unless there are concerning symptoms.
- For men and postmenopausal women, endoscopic evaluation is often warranted to rule out occult GI bleeding, as approximately a third of men and postmenopausal women presenting with IDA have an underlying pathological abnormality, most commonly in the GI tract 1. Iron deficiency without anemia still requires treatment as it can cause fatigue, reduced exercise capacity, hair loss, and cognitive issues due to iron's essential role in oxygen transport, DNA synthesis, and cellular metabolism 1. It is essential to note that iron supplementation in the presence of normal or even high ferritin values is not recommended and is potentially harmful 1. In cases where oral iron supplementation is not effective, IV iron administration may be considered, with ferric carboxymaltose being a well-studied option 1.
From the Research
Iron Deficiency without Anemia Workup
- Iron deficiency without anemia is a common condition that can cause symptoms such as fatigue, irritability, and difficulty concentrating 2
- The diagnosis of iron deficiency without anemia relies on a combination of tests, including:
- Haemoglobin concentration
- Haematocrit
- Mean cellular volume
- Mean cellular haemoglobin
- Percentage of hypochromic erythrocytes
- Serum ferritin levels 3
- A ferritin cut-off of 30 µg/l is appropriate for healthy males and females aged >15 years, while cut-offs of 15 and 20 µg/l are recommended for children from 6-12 years and younger adolescents from 12-15 years, respectively 3
- Testing for iron deficiency is indicated for patients with symptoms of iron deficiency (fatigue, pica, or restless legs syndrome) and should be considered for those with risk factors such as heavy menstrual bleeding, pregnancy, or inflammatory bowel disease 2
- Iron deficiency is diagnosed by low serum ferritin (typically <30 ng/mL) in individuals without inflammatory conditions or by transferrin saturation (iron/total iron binding capacity × 100) less than 20% 2
Treatment and Management
- Oral iron therapy is usually the first step in treatment, combined with counselling on dietary changes to increase iron intake 3
- Integrating haem and free iron regularly into the diet, looking for enhancers and avoiding inhibitors of iron uptake is beneficial 3
- Intravenous iron is indicated for patients with oral iron intolerance, poor absorption, chronic inflammatory conditions, ongoing blood loss, and during the second and third trimesters of pregnancy 2
- Iron studies should be repeated after 8 to 10 weeks of treatment to measure the success of treatment, and patients with repeatedly low ferritin may benefit from intermittent oral substitution to preserve iron stores 3
Clinical Considerations
- Iron deficiency without anemia can be challenging to diagnose and treat, especially in patients with underlying diseases 4
- Long-standing iron deficiency may be challenging to treat, and further investigations are needed if the iron deficiency has not been corrected after treatment 5
- There is limited evidence about the benefits of giving iron to people who do not have anaemia, but most people can be given oral iron supplements if there is iron deficiency 5