From the Guidelines
Refractory low ferritin and low transferrin saturation are typically caused by persistent iron deficiency despite treatment attempts, and the most recent evidence suggests that ongoing blood loss, malabsorption disorders, and inadequate iron supplementation are common causes. The most common causes include ongoing blood loss (particularly gastrointestinal bleeding from ulcers, malignancies, or inflammatory bowel disease), malabsorption disorders (celiac disease, gastric bypass surgery, H. pylori infection), inadequate iron supplementation, poor medication adherence, or concurrent conditions that increase iron requirements 1.
Causes of Refractory Iron Deficiency
- Ongoing blood loss: gastrointestinal bleeding from ulcers, malignancies, or inflammatory bowel disease
- Malabsorption disorders: celiac disease, gastric bypass surgery, H. pylori infection
- Inadequate iron supplementation
- Poor medication adherence
- Concurrent conditions that increase iron requirements
Diagnosis and Treatment
For treatment, oral iron supplements like ferrous sulfate 325mg taken 1-2 times daily between meals with vitamin C to enhance absorption is recommended. For patients not responding to oral therapy, intravenous iron formulations such as iron sucrose or ferric carboxymaltose may be necessary 1. Patients should undergo thorough evaluation including complete blood count, comprehensive metabolic panel, and tests for occult blood loss. Endoscopic evaluation may be warranted if gastrointestinal blood loss is suspected. Additionally, testing for celiac disease, H. pylori infection, and assessment of inflammatory markers can help identify underlying causes. Iron therapy typically requires 3-6 months to replenish stores, with follow-up ferritin measurements recommended after 8-12 weeks of treatment 1.
Monitoring and Follow-up
The frequency with which lab monitoring is required post-IV iron infusion is dependent on the cause of the ID. Those with recurrent blood loss will require more frequent and aggressive laboratory monitoring to diagnose and treat ID even in the absence of anemia since ID in the absence of anemia can lead to clinical complications 1. Patients with an inappropriate response to IV iron should be evaluated for ongoing blood loss or an alternative diagnosis for ID (true and functional).
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Causes of Refractory Low Ferritin and % Saturation
The causes of refractory low ferritin and % saturation can be complex and multifaceted. Some possible causes include:
- Iron deficiency, which can be due to inadequate dietary intake, increased requirements, or chronic blood loss 2, 3, 4
- Chronic inflammatory diseases, which can lead to anemia of chronic disease and low ferritin levels 2, 3
- Heart failure, which can lead to iron deficiency and low % saturation 3
- Other medical conditions, such as sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome, which can affect iron metabolism and ferritin levels 5
Diagnostic Criteria
The diagnostic criteria for iron deficiency and overload are not always clear-cut. Some studies suggest that:
- Serum ferritin concentration can be used as an index of iron deficiency and overload, but its accuracy can be affected by inflammation and other factors 4
- Transferrin saturation can be a useful indicator of iron deficiency, especially in patients with chronic heart failure 3
- A combination of serum ferritin and transferrin saturation may be more accurate than either test alone in diagnosing iron deficiency and overload 2, 6
Relationship between Iron Absorption and Ferritin
The relationship between iron absorption and ferritin levels is complex. Some studies have found that:
- Iron absorption is correlated with serum ferritin concentration, but this correlation is not always strong 6
- Transferrin saturation can be a useful indicator of iron absorption, especially in iron-depleted subjects 6
- Serum ferritin concentration can reflect iron stores and control iron absorption in iron-replete subjects 6