Anemia of chronic disease (ACD) is the second most common cause of anemia after iron deficiency anemia (IDA). It is typically mild to moderate in severity and is associated with chronic infections, inflammatory conditions, malignancies, and chronic kidney disease (CKD) .
Etiology & Associated Conditions
- Chronic infections : e.g., HIV/AIDS, tuberculosis, osteomyelitis
- Chronic inflammatory disorders : rheumatoid arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), vasculitis, sarcoidosis
- Malignancies : both hematologic and solid tumors
- Chronic kidney disease
- Organ transplantation : chronic graft rejection
Pathophysiology
Inflammation leads to multiple disturbances in iron metabolism and erythropoiesis:
1. Hepcidin-Mediated Iron Sequestration
- IL-6 → ↑ Hepcidin (liver)
- Hepcidin inhibits ferroportin (iron exporter in macrophages & enterocytes) → ↓ iron release to plasma
- Iron is trapped in macrophages of the reticuloendothelial system → functional iron deficiency
2. Reduced Erythropoiesis
- Inflammatory cytokines (IL-1, IL-6, TNF-α, IFN-γ) suppress erythroid progenitor cells
- Shortened RBC survival
3. Erythropoietin Resistance
- Blunted or inadequate erythropoietin (EPO) response relative to anemia severity
- In CKD, EPO production is intrinsically reduced
Laboratory Findings
| Test | ACD | Iron Deficiency Anemia (IDA) |
|---|---|---|
| Serum Iron | ↓ | ↓↓↓ |
| TIBC | ↓ or normal | ↑ |
| Ferritin | ↑ or normal | ↓ |
| Transferrin Saturation | ↓ | ↓↓↓ |
| RDW | Normal or mildly ↑ | ↑ |
| MCV | Normocytic or microcytic | Microcytic |
| Bone Marrow Iron | Normal or ↑ | Absent |
Ferritin is an acute phase reactant and is typically elevated in ACD, helping distinguish it from IDA.
Diagnosis
- Clinical context : Known chronic inflammatory or malignant condition
- Iron studies : Low serum iron, low TIBC, normal or high ferritin
- Rule out iron deficiency anemia : Consider checking soluble transferrin receptor (sTfR) or bone marrow biopsy if diagnosis is unclear
- CKD-specific : Measure serum erythropoietin levels if indicated
Differential Diagnosis
- Iron deficiency anemia
- Thalassemias
- Myelodysplastic syndromes
- Sideroblastic anemia
- Anemia of critical illness
Treatment
1. Treat Underlying Condition
- Management of infection, autoimmune disease, or malignancy
2. Erythropoiesis-Stimulating Agents (ESAs)
- Epoetin alfa or darbepoetin alfa
- Primarily used in:
- CKD-associated anemia
- Cancer-related anemia (with caution)
Use with iron supplementation if iron-restricted erythropoiesis is present.
3. Iron Therapy
- Only if concurrent true iron deficiency is documented
- IV iron preferred in patients on dialysis or those with inflammation-induced impaired oral absorption
4. Blood Transfusion
- Reserved for severe symptomatic anemia or hemodynamically unstable patients
- Avoid routine transfusion in critically ill unless Hb < 7–8 g/dL
Anemia of Critical Illness
- Common in ICU patients by day 3 of admission
- Caused by:
- Suppressed EPO response
- Cytokine-induced bone marrow suppression
- Frequent phlebotomy
- Managed with restrictive transfusion strategy
High-Yield Pearls
- ACD is not due to iron deficiency , but rather iron trapping and impaired utilization.
- Hepcidin is the key mediator of iron dysregulation.
- Normocytic, normochromic anemia is typical, but microcytosis may occur with chronicity.
- Ferritin helps differentiate ACD from IDA : it is elevated in ACD , low in IDA .
- Always assess for co-existing iron deficiency in patients with ACD.
