What is anemia of acute infection and how should it be managed?

Anemia of Acute Infection: Definition and Management

Anemia of acute infection is a distinct clinical entity characterized by inflammation-induced hypoferremia, impaired erythropoiesis, shortened red cell survival, and blunted erythropoietin production—and management prioritizes treating the underlying infection while using restrictive transfusion thresholds (hemoglobin <7 g/dL) in most patients. 1, 2, 3

Pathophysiology and Clinical Recognition

Anemia of acute infection develops through several interconnected mechanisms driven by the inflammatory response:

• Hepcidin overexpression is the master regulator, causing iron sequestration in macrophages and hepatocytes, leading to hypoferremia despite adequate or increased iron stores 3
• Cytokine-mediated suppression (TNF, IL-1, IL-6) directly inhibits erythropoiesis and blunts the normal erythropoietin response to low hemoglobin 1, 3
• Enhanced erythrophagocytosis by activated macrophages (M1 cells) accelerates red cell destruction, particularly in the liver and spleen 4
• Shortened red cell survival occurs even after the acute infectious episode resolves, with continued hemoglobin decline for several weeks 5

The severity of anemia does not always correlate with infection severity, and approximately 30-40% of critically ill patients with infection develop moderately severe anemia (Hb <9 g/dL) during their illness 2, 6.

Primary Management Strategy: Treat the Underlying Infection

The most critical intervention is optimizing treatment of the underlying infection, as successful control of the infectious process improves the anemia without specific anemia-directed therapy. 1, 3

• Inflammatory mediators alter iron metabolism and erythropoiesis, so inducing complete remission of infection is paramount 1
• Disease activity may not always correlate with elevated acute phase proteins (CRP), requiring clinical vigilance 1
• The anemia will not respond to iron supplementation despite low serum iron, as this represents functional iron deficiency from sequestration, not true deficiency 1

Transfusion Management: Restrictive Strategy

Transfuse at hemoglobin <7 g/dL (70 g/L) for most patients with acute infection, as restrictive strategies reduce mortality, morbidity, and infection risk compared to liberal approaches. 2, 7

Standard Transfusion Thresholds

• Hemoglobin <7 g/dL is the trigger for stable patients without cardiovascular disease, including those with septic shock and ARDS 2
• Hemoglobin <8 g/dL should be considered for patients with acute coronary syndrome or ischemic heart disease 2, 7
• Transfuse one unit at a time, then reassess hemoglobin before additional units, as each unit increases hemoglobin by approximately 1 g/dL 2, 7

Critical Context: Anemia Increases Infection Risk

Recent evidence demonstrates that anemia itself increases susceptibility to infections through multiple mechanisms:

• Immune dysfunction results from impaired innate and adaptive immune responses, plus increased gut permeability facilitating bacterial translocation 1
• Transient immunosuppression is compounded when anemia coexists with acute illness, diminishing the host's ability to mount effective immune responses 1
• Liberal transfusion strategies (targeting Hb >10 g/dL) paradoxically reduce sepsis risk in acute brain injury patients, though this finding requires further validation in general infection populations 1

Transfusion Risks to Consider

RBC transfusion carries substantial risks that must be weighed against benefits:

• Increased infection rates due to transfusion-related immunomodulation (TRIM) 1, 2
• Multi-organ failure, transfusion-related acute lung injury (TRALI), and circulatory overload (TACO) 1, 2
• Fluid overload and pulmonary edema, particularly in critically ill patients 1
• Use leuko-depleted blood when available, as it may reduce transfusion-related complications 1, 2

Pharmacologic Therapy: Limited Role

Erythropoietin and iron supplementation have no routine role in acute infection-associated anemia and should be avoided. 2

• Erythropoietin is not supported by evidence in general critically ill populations and should only be considered specifically in trauma patients without contraindications 2
• Iron therapy should be avoided except when administered concurrently with erythropoietin, as iron sequestration is the problem, not deficiency 1, 2
• Iron supplementation will not improve anemia in this context and carries potential risk of lifetime iron overload if transfusions become necessary 1

Prevention of Iatrogenic Worsening

Implement blood conservation strategies to prevent phlebotomy-induced anemia worsening during acute illness. 2

• Use small-volume blood collection tubes to minimize diagnostic blood loss 2
• Avoid standing orders for routine blood draws—order only necessary tests 2
• Monitor hemoglobin weekly after initiating therapy until stable, then at least monthly, as hemoglobin drops by mean 0.52 g/L per day in ICU patients 2

Monitoring and Reassessment

• Exclude other concurrent causes of anemia including malignancy, medication side effects (particularly thiopurines causing macrocytosis), and other infections 1
• Hemoglobin should be rechecked 1 hour post-transfusion to confirm adequate response, then monitored daily until stable above 7-8 g/dL 7
• More than half of patients anemic at ICU discharge remain anemic 6 months later, requiring longitudinal follow-up 2

Critical Pitfalls to Avoid

• Never target hemoglobin >11 g/dL, as this increases mortality, stroke, myocardial infarction, and thromboembolism without improving outcomes 2
• Do not delay transfusion in patients with hemoglobin <7 g/dL with respiratory symptoms or hemodynamic instability while awaiting diagnostic results—this represents a life-threatening emergency 2
• Do not give medicinal iron unless iron deficiency is biochemically proven, as pica is common in chronic illness but unrelated to iron status 1
• Recognize that successful infection treatment is the definitive therapy—anemia-specific interventions are supportive only 1, 3