8 Anemia of Inflammation
- AI = most common anemia in malignancy, autoimmune dz, chronic infection
- Labs: normo/microcytic, ↓ retic, ↓ Fe, ↓/normal TSAT, normal/↑ ferritin
- Path: IL-6 → ↑ hepcidin → Fe sequestration (iron-restricted erythropoiesis)
- Tx: treat underlying dz; IV Fe only if concurrent IDA proven
8.1 Overview
- AI = most common anemia cause in inflammatory dz worldwide (2nd after IDA)
- Etiologies: malignancy, autoimmune dz, chronic infection, trauma, acute illness
- Children: minor bacterial/viral infection → mild normocytic anemia w/ blunted retic (self-limited)
- Also: COPD, CHF, obesity, aging → chronic systemic inflammation
8.2 Pathophysiology
Cytokine-mediated: - IL-6, TNF, IFN-γ → ↓ EPO production relative to Hb level - ↓ EPO responsiveness - ↓ BM precursor survival
Hepcidin-iron axis (central): - Hepcidin = iron regulatory hormone (↑ by inflammation via STAT3) - Binds ferroportin → ↓ GI iron absorption & ↓ Fe release from macrophages - Results: iron sequestration in macrophages/hepatocytes = iron-restricted erythropoiesis
8.3 Diagnosis
Clinical: normo/microcytic anemia (Hb 7-11) in inflammatory dz background - Evolves: microcytic & hypochromic over time - Blunted retic count is key
Labs:
| Parameter | AI | IDA | AI/IDA |
|---|---|---|---|
| Ferritin | Normal/↑ | ↓ | ↑ |
| Serum Fe | ↓ | ↓ | ↓ |
| TSAT (%) | ↓ | ↓ | ↓ |
| TIBC | Normal/↓ | ↑ | Normal |
| MCV | Normal/↓ | ↓ | ↓ |
| RDW | Normal/↑ | ↑ | ↑ |
| sTfR | <2 | ↑ | ↑ |
| % Hypochromic RBCs | Normal/↓ | ↑ | ↑ |
Key distinction: - ↑ ferritin = expected in AI (acute phase reactant), argues AGAINST IDA alone - sTfR/log ferritin ratio > useful when inflammatory stress present - AI/IDA: sTfR ≥2; AI alone: sTfR <1
8.4 Treatment
Primary: - Treat underlying dz (cornerstone) - Hb improvement = better indicator of dz control than Fe supplementation alone
Iron supplementation: - Only if AI/IDA proven (not just suspected) - Confirm: sTfR ↑, TSAT <20%, hypochromic RBCs, RBC Hb content ↓ - IV Fe > PO (↑ hepcidin limits absorption); expect slow response - Response: gradual Hb ↑ over weeks (competing AI effects)
Erythropoietin-stimulating agents (ESAs): - Limited use outside CKD/myelofibrosis (not approved for AI alone) - ↑ adverse events w/ malignancy; caution w/ Hb correction
Future: - JAK inhibitors (baricitinib, momelotinib): ↓ hepcidin → Fe availability ↑ - Hepcidin-ferroportin axis targeting (trials ongoing)
- ↑ ferritin = argues AGAINST IDA alone (reflects inflammation, not Fe stores)
- Distinguish: true IDA (ferritin ↓, TIBC ↑) vs. IDA/AI combo (ferritin normal/↑, TIBC normal)
- Document hypochromia (RBC Hb content, % hypochromic RBCs) before Fe supplementation