Iron deficiency anemia (IDA) is the most common form of anemia worldwide, with a prevalence of 25% in adult males and menopausal women in developed countries, a higher incidence in menstruating women and children, and more common in developing countries. The most common cause of IDA in menstruating women is excessive menstruation, while the most common cause in adult men and menopausal women is gastrointestinal bleeding. It is particularly important to rule out asymptomatic colon and gastric cancers, which may be present in IDA patients. Other IDA etiologies include malabsorption, poor diet, gastrectomy and NSAID application.
I. Importance of gastrointestinal examination.
All male patients diagnosed with IDA and postmenopausal female patients should have a GI examination. When there are no obvious symptoms, the order of examination can be performed gradually according to the specific situation. When the patient has serious complications or is too old for further examination, especially when the results have little impact on treatment, the choice of examination method can be made according to the wishes of the patient and family.
All patients should be monitored for abdominal disease. Commonly used serologic methods for abdominal disease include anti-endomysial antibodies (EMA) and transglutaminase (tTG). If serology is negative, a small bowel biopsy at the time of esophagogastroduodenoscopy (OGD) is not required unless other manifestations of abdominal disease are suspected. If serology is positive, there is a high probability of abdominal disease and a small bowel biopsy should be performed. In this case, other GI tests, including colonoscopy, are not necessary. Patients with abdominal disease have a high likelihood of developing GI tumors during their lifetime, and if IDA occurs in patients with systemically treated abdominal disease, a GI exam should be performed.
If an OGD is performed first when performing a GI examination and gastric cancer or abdominal disease is detected, the lower GI examination can be discontinued. If esophagitis, reflux and peptic ulcer are present, lower GI examination should also be continued. If serology is positive or undetected, a small bowel biopsy should be performed at the time of OGD. Colonoscopy can detect abnormal vascular development and perform biopsies, both of which should be performed if there are no contraindications. However, the double-contrast barium enema method is also a good option in cases where colonoscopy is not available.
II. Diagnosis of iron deficiency anemia.
Microcytic anemia (mean red blood cell volume less than the normal range) is characteristic of IDA, but other rare diseases can have microcytic anemia, such as thalassemia. Microcytic anemia may also be present in hemoglobinopathies, but these disorders are uncommon and require specific laboratory tests to verify. In mixed nutritional deficiencies, MCV may be normal but mean red cell distribution width (RDW) is elevated. Microcytic anemia may also be present in some chronic disease anemias.
Serum ferritin level is the most specific indicator for the diagnosis of IDA. With a serum ferritin level of 100µg/dl, the diagnosis of IDA can be basically ruled out. If IDA is still highly suspected, further bone marrow examination or diagnostic treatment for 3 weeks may be indicated. Serum transferrin receptor and ferritin ratio may be of some significance in the differentiation of IDA and chronic disease anemia.
Third, the treatment of iron deficiency anemia.
1.Oral iron therapy.
Oral iron therapy is generally chosen over intravenous iron in case of iron deficiency. Theoretically, iron is well absorbed on an empty stomach, and the absorption of iron is three times higher on an empty stomach than during or after a meal. The absorption of iron is poor after atrophic gastritis, application of drugs that chronically inhibit the secretion of gastric acid and gastric surgery. However, the main obstacle to the application of oral iron therapy is nausea and gastric discomfort 30-60 minutes after taking the drug. This prevents many patients from adhering to the drug for a long period of time. Gastrointestinal symptoms are dose-related and are reduced after 2-3 days of continuous application. Lower doses and bedtime dosing can reduce discomfort. Diarrhea and constipation are dose-independent and can be managed symptomatically. Various iron supplements currently focus on reducing gastrointestinal side effects but are poorly absorbed. In the first 2-3 weeks of the patient’s application of iron therapy should focus on the treatment of side effects and improve patient compliance.
2.Iron for injection.
The main indications for iron for injection are uncontrollable blood loss, intolerance of oral iron, impaired gastrointestinal absorption and poor compliance. If the patient applies ferrous sulfate supplementation 60 mg iron 1-2 hours to detect a rise in serum iron less than 100 μg%, the application is considered malabsorption.
3.Ferrous dextrose.
Iron dextrose is currently the most used injectable iron, it is a low molecular weight dextrose complex with iron oxide, a dark brown solution, containing 50mg of iron per ml. although intramuscular injection can also be applied, but currently the vast majority of doctors intravenous application, so that a larger dose can be applied. For patients on hemodialysis, injectable iron dextran can be applied 6-10 times continuously at 100 mg each. in special cases, the maximum single dose can be up to 500C2000 mg. after application of anti-allergic drugs, dissolve iron dextran in 500 mL of saline and drip slowly intravenously, starting slowly at about 20-30 mL for 5 minutes. If there is no allergic reaction, the remaining dose is given over 3-4 hours. There is a risk of death due to anaphylaxis from iron dextrose and allergy testing is important. About 10% of patients also develop myalgia, arthralgia, headache and general discomfort 24-48 hours after application of iron dextrose. Non-steroidal anti-inflammatory drugs can relieve these symptoms.
4. Sodium ferric glucose (Sodiumferricgluconate, SFG).
Sodium ferric glucose is a stable sucrose macromolecular complex in a deep red solution. It contains 62.5 mg of elemental iron per 5 mL dose. It can be administered directly intravenously at 12.5 mg per minute for a total of 125 mg for 10. No allergy testing is required. While iron dextran may take several weeks to be fully absorbed by the macrophage system after injection, sodium ferric glucose is 80% available for distribution to transferrin within 24 hours and is absorbed and utilized significantly faster than iron dextran.
SFG has no hypersensitivity reactions and has a better safety profile. the WHO published data showing that 25 million patients injected with SFG did not result in death, compared with 31 deaths among 12 million patients applying deferoxamine. the results of a multicenter, randomized, crossover, double-blind controlled trial conducted in 2534 hemodialysis patients showed that the side effects of SFG application and placebo were similar, 12.3% and 9.8 percent. The results were compared with 3768 patients on historical desferrioxamine application, with lower rates of fatal events (requiring resuscitation) and drug intolerance in the SFG group, with only 1 fatal event in the SFG group compared with 23 in the desferrioxamine group, and 11 cases of drug intolerance in the SFG group compared with 64 in the desferrioxamine group. The results suggest that SFG should be used as an alternative to desferrioxamine for intravenous iron supplementation in hemodialysis patients. There are no such double-blind randomized controlled studies in other diseases, but SFG has a higher safety profile than desferrioxamine and is a good choice.
5. Iron sucrose.
FDA approved iron sucrose in 2000 and is the third intravenous iron supplement. There is less clinical information on its application than SFG. Iron sucrose is a brown liquid, 5mL contains 100mg of iron. A skin test is not required. It can either be administered directly intravenously or added to 100mL of saline for an intravenous drip over 15 minutes, which reduces the possibility of hypotension. The safety profile of iron sucrose is similar to that of SFG.