What is the difference between anemia of chronic disease and anemia of acute infection?

From the Guidelines

Anemia of acute infection differs from anemia of chronic infection primarily in its duration, severity, and underlying mechanisms, with chronic infection anemia requiring a more complex management approach that includes treating the underlying infection and sometimes supplementing with erythropoiesis-stimulating agents or iron, as guided by the most recent evidence from 2017 1.

Key Differences in Anemia of Acute and Chronic Infection

• Anemia of acute infection is typically mild and transient, lasting only days to weeks, and results from decreased red blood cell production due to inflammatory cytokines, increased red cell destruction, and sometimes blood loss.
• In contrast, chronic infection anemia persists for months to years and involves more complex pathophysiology, including iron sequestration in macrophages (functional iron deficiency), reduced erythropoietin production, and impaired bone marrow response.

Diagnostic Criteria

• Diagnostic criteria for iron deficiency depend on the level of inflammation, with a serum ferritin level < 30 mcg/L or transferrin saturation < 16% defining iron deficiency in patients without inflammation, and a serum ferritin level up to 100 mcg/L consistent with iron deficiency in the presence of inflammation 1.
• The diagnostic criteria for anemia of chronic disease (ACD) are a serum ferritin > 100 mcg/L and transferrin saturation < 16% in the presence of biochemical or clinical evidence of inflammation 1.

Management

• Management of anemia of chronic infection requires treating the underlying chronic infection while sometimes supplementing with erythropoiesis-stimulating agents like epoetin alfa or darbepoetin in severe cases, as recommended by the European Crohn's and Colitis Organization (ECCO) guidelines 1.
• Iron supplementation may be considered if concurrent true iron deficiency exists, but is generally not helpful for the functional iron deficiency of chronic infection, and should be guided by the patient's serum ferritin level and transferrin saturation 1.

Importance of Accurate Diagnosis

• The distinction between anemia of acute and chronic infection matters because misdiagnosing chronic infection anemia as simple iron deficiency can lead to inappropriate iron supplementation, which may worsen outcomes by providing iron to pathogens or exacerbating inflammation 1.
• Accurate diagnosis and management of anemia in patients with inflammatory bowel disease (IBD) can improve quality of life and reduce morbidity and mortality, as highlighted by the ECCO guidelines 1.

From the Research

Anemia of Acute versus Chronic Infection

• Anemia is a common finding in infected individuals, and its severity may not necessarily be proportional to the severity of the infection 2, 3.
• The term 'anemia of infection' refers to a specific syndrome related to the more broadly defined 'anemia of chronic disease' 3.
• Anemia of inflammation is the most common type of anemia in infection, due to over-expression of hepcidin 2.
• In chronic infections such as tuberculosis, anemia is common and multiple etiologies necessitate targeted interventions 4.
• The proportion of iron-responsive anemia due to iron deficiency compared with iron-unresponsive anemia due to impaired iron absorption/redistribution from tuberculosis-associated immune activation or inflammation is unknown 4.

Diagnosis and Treatment

• A clear understanding of the diverse causes of anemia and recognition that they often occur in combination can be of enormous assistance in forming a proper diagnosis and an appropriate management plan 2.
• The initial focus for the emergency evaluation of anemia is to determine whether the problem is acute or chronic 5.
• Acute anemia is most commonly associated with blood loss, and the patient is usually symptomatic, while chronic anemia is usually well tolerated and is often discovered coincidentally 5.
• In critical illness, standard treatment for anemia is red blood cell (RBC) transfusion, typically using a restrictive transfusion threshold of 70 g L-1 6.

Pathophysiology and Prevalence

• Cytokines produced as part of the host response to infection induce anemia by well-defined pathophysiological mechanisms 3.
• Anemia is more frequent in tuberculosis cases (67%) than in tuberculin skin test (TST)-positive (36%) or TST-negative (21%) controls 4.
• Anemia of inflammation (AI) is the predominant anemia at tuberculosis diagnosis, declining from 36% to 8% after 6 months of treatment 4.