Anemia in Tuberculosis: Primary Causes
The primary cause of anemia in tuberculosis is anemia of chronic disease (also called anemia of inflammation), which accounts for the vast majority of cases at TB diagnosis, though iron deficiency anemia and mixed forms are also common and clinically significant. 1, 2
Predominant Mechanism: Anemia of Inflammation
Anemia of inflammation (AI) is the dominant form at TB diagnosis, present in approximately 36% of patients with active TB, driven by immune activation and inflammatory cytokines that impair iron absorption and redistribute iron away from erythropoiesis 1
The inflammatory response in TB causes hepcidin elevation (median 84.0 ng/mL at diagnosis), which blocks iron absorption from the gut and traps iron in macrophages, making it unavailable for red blood cell production 1
Normochromic normocytic anemia is the characteristic pattern, found in 60.8% of anemic TB patients, reflecting the anemia of chronic disease mechanism 3
This form of anemia is directly linked to TB disease activity and typically resolves with effective TB treatment—AI prevalence drops from 36% to 8% after 6 months of standard TB chemotherapy 1
Iron Deficiency Component
Iron deficiency anemia (IDA) accounts for approximately 27.8% of anemia cases in TB patients, presenting as hypochromic microcytic anemia 3
More than half of TB-associated anemia at baseline is related to iron deficiency (mean corpuscular volume <80 fL), though this is often masked by concurrent inflammation 4
Multifactorial anemia (IDA+AI combined) represents a significant proportion of cases, where both iron deficiency and inflammatory mechanisms coexist 1
Critical distinction: IDA and mixed IDA+AI do NOT resolve with TB treatment alone—these forms persist even after 6 months of chemotherapy and require targeted iron supplementation 1
Clinical Significance and Mortality Risk
Anemia without iron deficiency increases TB recurrence risk 4-fold (adjusted RR = 4.10,95% CI = 1.88-8.91) 4
Iron deficiency without anemia increases mortality risk nearly 3-fold (adjusted RR = 2.89,95% CI = 1.53-5.47) 4
Anemia with or without iron deficiency increases death risk 2- to 3-fold independently of other factors 4
Anemia prevalence in TB is 61-67%, significantly higher than in tuberculin skin test-positive controls (36%) or negative controls (21%) 1, 3
Severity Markers and Associated Conditions
Anemia correlates with TB severity: more frequent in disseminated and meningeal TB, and associated with weight loss >10%, hospitalization, and HIV coinfection 3
Anemia of chronic disease (97.17%) vastly predominates over pure iron deficiency anemia (2.29%) when classified by iron biomarkers 2
Elevated inflammatory markers (ESR, CRP) and thrombocytosis are consistently associated with TB-related anemia 2, 3
Timing of Iron Intervention
A therapeutic window opens at 2 months into TB treatment, when hepcidin levels drop dramatically (from 84.0 ng/mL to 9.7 ng/mL), allowing iron absorption to resume 1
Iron supplementation should NOT be given at TB diagnosis due to concerns about bacterial iron utilization, but should be considered after 2 months when inflammation subsides and iron-responsive anemia persists 1
Monitor iron biomarkers (ferritin, sTfR, hepcidin) to distinguish AI from IDA and guide timing of iron therapy 1
Common Pitfall to Avoid
Do not assume all TB-associated anemia will resolve with TB treatment alone—while anemia of inflammation improves dramatically, iron deficiency anemia and mixed forms require specific iron supplementation starting around 2 months into treatment when inflammatory markers normalize 1. Failure to address persistent iron deficiency contributes to the 2- to 3-fold increased mortality risk in these patients 4.