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Anemia of Chronic Disease

Anemia of Chronic Disease (ACD) is a common type of anemia that develops in patients with chronic inflammation, infection, autoimmune disease, cancer, or chronic kidney disease. It occurs mainly because inflammation causes iron sequestration, reduced erythropoietin production, and impaired red blood cell production.

Also called

Anemia of Inflammation

ICD-10

D63.8

Specialty

Hematology

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

Anemia of Chronic Disease (ACD) is usually a mild-to-moderate anemia associated with chronic inflammatory conditions. Inflammation increases hepcidin, which traps iron inside macrophages and decreases intestinal iron absorption. As a result, iron becomes unavailable for red blood cell production despite adequate or increased total body iron stores.

Anemia of Chronic Disease (ACD) is typically normocytic and normochromic, but it may become mildly microcytic in prolonged disease.

Etiology & Risk Factors

-Chronic Inflammatory Conditions

  • Rheumatoid arthritis

  • Systemic lupus erythematosus

  • Inflammatory bowel disease

  • Chronic infections

  • Tuberculosis

  • Osteomyelitis

-Chronic Infections

  • HIV

  • Chronic bacterial infections

  • Chronic fungal infections

  • Endocarditis

-Malignancy

  • Solid tumors

  • Hematological malignancies

  • Lymphoma

  • Leukemia

-Chronic Organ Disease

  • Chronic kidney disease

  • Chronic liver disease

  • Heart failure

-Other Risk Factors

  • Advanced age

  • Long-standing inflammatory conditions

  • Autoimmune diseases

  • Chronic tissue injury

Pathophysiology

Chronic disease or inflammation → increased inflammatory cytokines, particularly IL-6 → increased hepatic hepcidin production → decreased intestinal iron absorption + iron trapped within macrophages → reduced iron availability for erythropoiesis → impaired hemoglobin synthesis → decreased red blood cell production → reduced erythropoietin response → shortened RBC survival → development of Anemia of Chronic Disease (ACD).

Clinical Presentation

-Symptoms

  • Fatigue

  • Weakness

  • Reduced exercise tolerance

  • Shortness of breath on exertion

  • Dizziness

  • Headache

  • Palpitations

-Signs

  • Pallor

  • Tachycardia

  • Signs of the underlying chronic disease

History Taking

Ask about:

  • Fatigue
  • Weakness
  • Exercise tolerance
  • Shortness of breath
  • Dizziness
  • Palpitations
  • Duration of symptoms
  • History of chronic inflammatory disease
  • Chronic infection
  • Cancer
  • Chronic kidney disease
  • Autoimmune disease
  • Inflammatory bowel disease
  • Recent infections
  • Medication history
  • Evidence of blood loss
  • Dietary history

Physical Examination

-General Examination

Look for:

  • Pallor

  • Tachycardia

  • Signs of chronic illness

  • Weight loss

  • Fever

-Systemic Examination

Look for signs of the underlying cause:

    • Joint swelling in rheumatoid arthritis

    • Lymphadenopathy in malignancy or infection

    • Organomegaly

    • Signs of chronic kidney disease

    • Signs of chronic liver disease

    • Signs of infection

Investigations

Complete Blood Count (CBC)

Typical findings:

  • Low hemoglobin

  • Usually normocytic

  • Usually normochromic

  • Mild microcytosis may occur

  • Low or normal reticulocyte count

Iron Studies

Typical pattern:

  • Serum iron: Low

  • Serum transferrin/TIBC: Low or normal

  • Serum ferritin: Normal or high

  • Transferrin saturation: Low

Inflammatory Markers

  • CRP ↑

  • ESR ↑

Renal Function

  • Urea

  • Creatinine

  • eGFR

Important for detecting chronic kidney disease as a contributing cause.

Peripheral Blood Film

Usually shows:

  • Normocytic, normochromic red cells

  • Mild microcytosis in some patients

Additional Investigations

Depending on clinical suspicion:

  • Vitamin B12

  • Folate

  • Thyroid function tests

  • Stool occult blood testing

  • Hemolysis screen

  • Bone marrow examination in unexplained cases

Diagnosis

IDA vs ACD · Aetiology & Mechanism

Parameter Iron Deficiency Anaemia (IDA) Anaemia of Chronic Disease (ACD)
Aetiology & Mechanism
Causes Blood loss (GI, menorrhagia, haematuria)
Malabsorption (coeliac, gastrectomy)
Increased demand (pregnancy, infancy)
Poor dietary intake		 Chronic inflammation, infection, malignancy
Rheumatoid arthritis, SLE, IBD
CKD, HIV, TB, heart failure
Major surgery / critical illness
Mechanism Absolute iron deficiency → inadequate haemoglobin synthesis → microcytic hypochromic RBCs Hepcidin ↑ (acute phase reactant) → blocks iron release from stores + reduces GI absorption → functional iron deficiency despite adequate stores

IDA vs ACD · CBC & Blood Film

Parameter Iron Deficiency Anaemia (IDA) Anaemia of Chronic Disease (ACD)
CBC & Blood Film
MCV ↓ Microcytic (<80 fL) Normal or ↓ mildly microcytic
Usually normocytic (80–100 fL)
MCH / MCHC ↓↓ Hypochromic Normal or mildly ↓
RDW ↑ Elevated (>14.5%) — anisocytosis Normal
Blood film Microcytes, hypochromia, pencil cells (elliptocytes), target cells, anisocytosis, poikilocytosis Normochromic normocytic (or mild hypochromia)
May show underlying disease features (e.g. rouleaux in myeloma)
Reticulocytes ↓ Low (bone marrow iron-starved) ↓ Low (suppressed by inflammation)

IDA vs ACD · Other Laboratory Findings

Parameter Iron Deficiency Anaemia (IDA) Anaemia of Chronic Disease (ACD)
Other Laboratory Findings
ESR / CRP Normal ↑ Elevated (underlying inflammation)
Platelets ↑ Reactive thrombocytosis common Variable — depends on underlying disease
WBC Normal Variable
Serum B12 / Folate Normal (unless mixed deficiency) Normal

IDA vs ACD · Iron Studies — Key Discriminator

Parameter Iron Deficiency Anaemia (IDA) Anaemia of Chronic Disease (ACD)
Iron Studies — Key Discriminator
Serum Iron ↓↓ Low ↓ Low
Serum Ferritin ↓↓ Low (<12 µg/L) — most specific for IDA ↑ Normal or High (acute phase reactant — falsely elevated even when iron-deficient)
TIBC / Transferrin ↑↑ High (liver upregulates transferrin to capture more iron) ↓ Low or normal (negative acute phase protein)
Transferrin Saturation ↓↓ <16% ↓ Low (<20%) but less severe
Serum Transferrin Receptor (sTfR) ↑ Elevated (cells upregulate TfR when starved of iron) Normal — key discriminator when ferritin is raised
Iron stores (bone marrow) Absent (depleted) Present but trapped (hepcidin blocks release)
Hepcidin ↓ Low (body tries to increase iron absorption) ↑↑ High (key driver — IL-6 stimulates liver to produce hepcidin)

IDA vs ACD · Clinical Features

Parameter Iron Deficiency Anaemia (IDA) Anaemia of Chronic Disease (ACD)
Clinical Features
Symptoms of anaemia Shared: fatigue, pallor, exertional dyspnea, palpitations, dizziness, headache
Specific to IDA Koilonychia (spoon nails)
Angular cheilitis
Atrophic glossitis (smooth red tongue)
Pica (craving ice, clay, dirt)
Plummer-Vinson syndrome (dysphagia + IDA + web)		 Features of underlying disease — joint swelling (RA), weight loss (malignancy), oedema (CKD/HF), night sweats (infection)
Severity of anaemia Can be severe if chronic blood loss Usually mild-moderate (Hb rarely <8 g/dL unless CKD)
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Related Topics

Management

1. Treat the Underlying Disease

The primary treatment is to control the underlying condition:

  • Treat chronic infection

  • Control inflammatory disease

  • Treat malignancy

  • Manage autoimmune disease

  • Optimize chronic kidney disease

2. Iron Therapy

Iron replacement is not routinely required unless true iron deficiency is also present.

Consider iron therapy when:

  • Iron deficiency coexists

  • Functional iron deficiency is significant

  • Chronic kidney disease is present and iron therapy is indicated

3. Erythropoiesis-Stimulating Agents (ESAs)

May be used in selected patients with:

  • Chronic kidney disease

  • Certain chemotherapy-associated anemias

Use requires careful assessment because of potential thromboembolic and cardiovascular risks.

4. Blood Transfusion

Reserved for:

  • Severe symptomatic anemia

  • Hemodynamic instability

  • Acute clinical deterioration

Complications

  • Persistent fatigue
  • Reduced exercise tolerance
  • Reduced quality of life
  • Worsening symptoms of the underlying disease
  • Cardiovascular strain in severe anemia
  • Increased morbidity in patients with significant chronic disease

Prognosis

The prognosis of Anemia of Chronic Disease (ACD) depends mainly on the underlying condition. The anemia often improves when the underlying inflammation or disease is successfully controlled. Persistent anemia may occur when the chronic disease remains active or when chronic kidney disease significantly reduces erythropoietin production.

Key Points / Clinical Pearls

  • Anemia of Chronic Disease (ACD) is caused by chronic inflammation or systemic disease.
  • Common causes include autoimmune disease, chronic infection, cancer, and chronic kidney disease.
  • Hepcidin is the key mediator.
    Hepcidin traps iron in macrophages and decreases intestinal iron absorption.
  • Iron is present in the body but is not adequately available for erythropoiesis.
  • Usually causes a normocytic, normochromic anemia.
  • Serum iron is low.
    Ferritin is usually normal or high.
    TIBC is usually low or normal.
  • Treat the underlying disease rather than routinely giving iron.
  • Always consider and exclude coexisting Iron Deficiency Anemia (IDA).