Do individuals with low hemoglobin (Hb) levels have an increased susceptibility to infections?

Do Low Hemoglobin Levels Increase Susceptibility to Infections?

Yes, low hemoglobin levels significantly increase susceptibility to infections through multiple mechanisms including impaired innate and adaptive immune responses, increased gut permeability facilitating bacterial translocation, and transient immunosuppression—effects that are particularly pronounced in critically ill patients and those with acute brain injury. 1

Mechanisms Linking Anemia to Infection Risk

The relationship between low hemoglobin and infection susceptibility operates through several interconnected pathways:

• Immune dysfunction occurs due to inflammation-induced erythropoietin suppression, oxidative stress, and nutrient deficiencies that compromise both innate and adaptive immune responses 1

• Increased gut permeability in anemic states facilitates bacterial translocation, particularly of pathogens such as Escherichia coli, creating a direct pathway for systemic infection 1

• Transient immunosuppression from anemia leads to suppression of cell-mediated immunity, which when combined with other conditions (like traumatic brain injury), compounds the immunosuppressive burden and diminishes the host's ability to mount effective immune responses 1

• Historical recognition of anemia as a risk factor for infections including tuberculosis and invasive bacterial infections supports this mechanistic understanding 1

Clinical Evidence from High-Quality Studies

The most recent and highest-quality evidence comes from a 2025 systematic review and meta-analysis in Critical Care examining 2,394 patients with acute brain injury:

• Restrictive transfusion strategies (maintaining lower hemoglobin thresholds) were associated with significantly higher rates of sepsis and septic shock compared to liberal transfusion strategies 1

• Lower baseline hemoglobin levels and progressive hemoglobin decline during early sepsis were linked to higher mortality risk 1

• The evidence quality for the association between anemia and sepsis risk was rated as high-quality using GRADE criteria 1

Specific Populations at Highest Risk

Pediatric Patients

• Children with anemia (regardless of etiology) are 5.75 times more susceptible to lower respiratory tract infections compared to non-anemic children 2
• Among anemic children with respiratory infections, 60% had iron deficiency, 10% had anemia of chronic inflammation, and 4% had hemolytic anemia 2

Cancer and Hematologic Malignancy Patients

• Multiple myeloma patients receiving bispecific antibody therapy commonly experience hypogammaglobulinemia, which increases infection risk with encapsulated bacteria and is associated with decreased overall survival 1
• High-grade non-Hodgkin's lymphoma patients face increased infection risk from leukopenia due to marrow infiltration, with multiple prior chemotherapy regimens significantly amplifying this risk 3

Critically Ill Patients

• The combination of anemia and critical illness creates a "two-hit" phenomenon where both conditions independently suppress immunity, and their coexistence compounds the immunosuppressive burden 1

Clinical Implications and Management Approach

When to Suspect Infection Risk from Anemia

Immediate evaluation is warranted when:

• Hemoglobin drops below 10 g/dL in any hospitalized patient, particularly those with concurrent inflammatory conditions 1
• Progressive hemoglobin decline occurs during acute illness or sepsis 1
• Patients develop fever with absolute neutrophil count <500 cells/µL (febrile neutropenia—a medical emergency requiring immediate empiric antibiotics) 4

Transfusion Threshold Considerations

The evidence suggests maintaining higher hemoglobin thresholds in high-risk populations:

• For acute brain injury patients: Liberal transfusion strategies (higher hemoglobin targets) reduce sepsis risk and improve neurological outcomes compared to restrictive strategies 1

• For general critically ill patients: While hemoglobin of 7 g/dL may be tolerated in stable patients, this threshold may be inadequate for those with preexisting coronary, cerebrovascular, or pulmonary disease 1

• For cancer patients on chemotherapy: Consider erythropoiesis-stimulating agents when hemoglobin falls below 10 g/dL to prevent transfusions and their associated complications including immune suppression 1

Critical Pitfalls to Avoid

• Do not attribute anemia solely to "anemia of chronic disease" without recognizing that this represents activated immune dysfunction that increases infection susceptibility 5

• Avoid iron supplementation alone in patients with anemia of chronic disease, as iron promotes microbial growth and inhibits T-cell-mediated immune pathways 5

• Do not delay antimicrobial therapy in anemic patients with suspected infection while attempting to correct hemoglobin levels—address both simultaneously 3

• Recognize that plasma volume expansion (not true hemoglobin deficiency) can cause apparent anemia in heart failure and liver disease patients, where measuring total hemoglobin mass may prevent inappropriate interventions 6

Monitoring Strategy for High-Risk Patients

• Weekly CBC monitoring for the first 4-6 weeks in patients on immunosuppressive therapy or with unexplained anemia patterns 4

• Immediate re-evaluation if patients develop fever, new infections, or worsening cytopenias 4

• Monthly immunoglobulin level monitoring in cancer patients with hypogammaglobulinemia (IgG <400 mg/dL), as serum levels alone do not adequately inform on antibody response capacity 1