Hematological Findings in Tuberculosis (TB)

For MD Examinations — Comprehensive 15-Mark Answer

Introduction

I. ANEMIA (Most Common — ~60–80% of Cases)

A. Anemia of Chronic Disease (ACD) / Anemia of Inflammation

• Most common type in TB
• Caused by:
  • Elevated hepcidin (acute-phase reactant) → blocks ferroportin → iron sequestration in macrophages
  • Increased pro-inflammatory cytokines (IL-6, TNF-α, IL-1) → suppress erythropoietin production
  • Decreased RBC lifespan due to cytokine-mediated hemolysis
• Morphology: Normocytic normochromic (early) → microcytic hypochromic (later)
• Iron studies: Serum iron ↓, TIBC ↓, serum ferritin ↑ (differentiates from iron-deficiency)

B. Iron Deficiency Anemia

• Due to poor nutritional intake, malabsorption (intestinal TB)
• Microcytic hypochromic picture with ↓ serum ferritin

C. Megaloblastic Anemia

• Due to deficiency of folate (poor intake, increased utilization during infection)
• Also caused by pyrazinamide (folate antagonism) and isoniazid (B6 interference → indirect folate metabolism effect)
• Hypersegmented neutrophils, macro-ovalocytes on peripheral smear

D. Hemolytic Anemia

• Rarely, autoimmune hemolytic anemia (AIHA) can complicate TB
• Rifampicin can cause immune-mediated hemolytic anemia (drug-induced)

E. Aplastic/Hypoplastic Anemia

• Due to bone marrow infiltration in miliary TB
• Pancytopenia may result

II. WHITE BLOOD CELL (WBC) CHANGES

A. Leukocytosis

• Seen in active pulmonary and extrapulmonary TB
• Usually moderate (10,000–20,000/μL)
• Neutrophilic leukocytosis in acute/miliary TB
• Can mimic bacterial infection

B. Leukopenia

• Seen in severe/miliary TB with bone marrow suppression
• Also caused by anti-TB drugs (especially rifampicin, isoniazid)
• Important poor prognostic sign in miliary TB

C. Lymphocytosis

• Characteristic of chronic TB (reflects cell-mediated immune response)
• Seen in TB meningitis CSF (lymphocytic pleocytosis)
• Reactive lymphocytes may appear in peripheral blood

D. Lymphopenia

• Seen in advanced HIV-TB co-infection and severe miliary TB
• Associated with poor prognosis

E. Monocytosis

• Common in active TB (10–20% of WBC count)
• Reflects macrophage activation and granuloma formation
• A classic peripheral smear feature of TB

F. Neutropenia

• Drug-induced — rifampicin, isoniazid, pyrazinamide can suppress marrow neutrophil production

III. PLATELET CHANGES

A. Thrombocytosis (Reactive)

• Common in active TB — platelets may rise to 500,000–800,000/μL
• Mechanism: IL-6 → stimulates thrombopoietin → megakaryocyte proliferation
• Acts as an acute-phase reactant
• Resolves with treatment

B. Thrombocytopenia

• Occurs in:
  • Miliary TB with bone marrow infiltration
  • Disseminated Intravascular Coagulation (DIC) in severe TB
  • Drug-induced (rifampicin is the classic cause — immune-mediated destruction)
  • Hypersplenism (in TB with splenomegaly)
• Rifampicin-induced thrombocytopenia: IgG antibodies against platelet-rifampicin complex → sudden drop on re-challenge

IV. ERYTHROCYTE SEDIMENTATION RATE (ESR)

• Markedly elevated (often > 100 mm/hr) in active TB
• One of the most sensitive markers of active disease
• Elevated due to:
  • Fibrinogen ↑ (acute-phase protein)
  • Globulins ↑ (hypergammaglobulinemia)
  • Anemia (low PCV → reduced plasma viscosity effect)
• Serial ESR is used to monitor treatment response — it falls progressively with effective therapy
• Not specific — elevated in any chronic infection/inflammation

V. BONE MARROW CHANGES

Note: Bone marrow biopsy is particularly valuable for diagnosing miliary TB — granulomas are found in up to 75% of miliary TB cases and AFB staining may be positive.

VI. COAGULATION ABNORMALITIES

• DIC can complicate miliary or severe TB
  • Prolonged PT, APTT
  • ↑ D-dimer, fibrin degradation products
  • Thrombocytopenia + microangiopathic hemolytic anemia (MAHA)
• Hypercoagulable state:
  • TB is associated with venous thromboembolism (DVT/PE)
  • Mechanism: pro-inflammatory state → ↑ fibrinogen, ↑ PAI-1, platelet activation
  • Anti-phospholipid antibodies may appear transiently

VII. PLASMA PROTEIN CHANGES

VIII. HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)

• TB is a recognized trigger of HLH (reactive/secondary)
• Features:
  • Fever, splenomegaly
  • Pancytopenia (anemia + thrombocytopenia + leukopenia)
  • ↑ Serum ferritin (often > 10,000 ng/mL)
  • Hemophagocytosis on bone marrow biopsy
• Important to recognize as it carries high mortality if untreated

IX. DRUG-INDUCED HEMATOLOGICAL TOXICITY

X. PERIPHERAL BLOOD SMEAR SUMMARY

XI. SUMMARY TABLE FOR QUICK REVISION

Key Exam Points

1. Anemia of chronic disease is the most common hematological finding in TB — normocytic/normochromic with normal/elevated ferritin.
2. Monocytosis is a classic and characteristic finding in peripheral blood.
3. Miliary TB = pancytopenia due to bone marrow infiltration with granulomas.
4. Rifampicin is the classic cause of drug-induced thrombocytopenia in TB.
5. Isoniazid causes sideroblastic anemia by depleting pyridoxine (B6).
6. ESR > 100 mm/hr is a typical feature of active TB and falls with treatment.
7. Reactive thrombocytosis via IL-6/thrombopoietin axis is common in active TB.
8. HLH should be considered when TB presents with high fever + pancytopenia + very high ferritin.
9. Bone marrow biopsy is the investigation of choice in suspected miliary TB with cytopenias.
10. Linezolid (used in MDR/XDR-TB) causes the most severe hematological toxicity.