Adenosine Deaminase (ADA)(Pleural fluid)

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Diagnose tuberculous pleural effusion, especially in high TB-burden countries like India

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Adenosine Deaminase (ADA) - Pleural Fluid

Why is it done?
- ADA is an enzyme produced by lymphocytes, particularly T cells, and is measured in pleural fluid to aid in the diagnosis of tuberculous pleural effusion and other lymphocytic pleural diseases
- Primary indications include suspected tuberculosis (TB) infection in pleural fluid, differentiation between tuberculous and non-tuberculous pleural effusions, and evaluation of lymphocytic exudates of unknown etiology
- This test is typically performed when a patient presents with pleural effusion and clinical suspicion for tuberculosis, or when pleural fluid analysis reveals lymphocyte predominance with unclear etiology
- ADA measurement is particularly valuable in endemic tuberculosis regions and helps guide diagnostic decisions when tuberculosis culture results are pending or negative
Normal Range
- Normal/Reference range: <10 U/L (units per liter)
- Borderline elevated: 10-40 U/L
- Elevated (suggestive of TB): >10 U/L (most sources cite >4-6 U/L as cutoff)
- Units of measurement: International Units per Liter (U/L) or IU/mL
- Normal result: ADA activity <10 U/L indicates low lymphocytic enzyme activity, making tuberculous etiology less likely; however, sensitivity and specificity vary by cutoff used
- Abnormal result: Elevated ADA (typically >10 U/L) suggests lymphocytic inflammation, highly suggestive of tuberculosis in appropriate clinical context; can also be seen in other conditions causing lymphocytic pleural effusions
Interpretation
- ADA <4 U/L: Tuberculosis is unlikely; consider other etiologies such as malignancy, heart failure, pneumonia, pulmonary embolism, or other inflammatory conditions
- ADA 4-10 U/L: Intermediate zone; TB possible but not confirmed; further investigation with cultures, PCR, and clinical correlation needed; sensitivity approximately 60-80%
- ADA >10 U/L (especially >40 U/L): Highly suggestive of tuberculous pleural effusion in appropriate clinical context; sensitivity 90-95%, specificity 85-95% depending on cutoff and population; start anti-TB therapy if clinical suspicion is high
- False positives can occur with other lymphocytic conditions: systemic lupus erythematosus (SLE), rheumatoid pleural effusion, viral infections, lymphoma, and fungal infections (histoplasmosis, coccidioidomycosis)
- False negatives can occur in early TB (immune suppression, especially HIV with CD4 <50), TB with predominant neutrophils, or technical issues with sample handling
- Factors affecting results: lymphocyte count in pleural fluid, proper sample collection and preservation, degree of immune response, presence of HIV co-infection, and geographic prevalence of TB in the population
- Clinical significance: Results should always be interpreted alongside clinical presentation, pleural fluid characteristics (lymphocytic exudate), pleural biopsy findings, tuberculin skin test, chest imaging, and culture/PCR results
Associated Organs
- Primary organ system: Respiratory/pulmonary system; pleural space and lungs
- Immune system involvement: T lymphocytes and other inflammatory cells produce and release ADA during immune response
- Diseases commonly associated with abnormal results:
- Tuberculous pleural effusion (primary indication)
- Systemic lupus erythematosus with pleural involvement
- Rheumatoid pleural disease
- Fungal infections (histoplasmosis, coccidioidomycosis, blastomycosis)
- Viral infections with lymphocytic pleural response
- Lymphoma with pleural involvement
- Empyema and other bacterial infections
- Potential complications associated with abnormal results:
- Untreated tuberculosis can progress to disseminated disease, tuberculous meningitis, military TB, and organ dysfunction
- Pleural effusion can lead to dyspnea, respiratory compromise, and hemodynamic changes if large
- Delays in diagnosis due to false negative results can compromise patient outcomes and increase transmission risk
Follow-up Tests
- If ADA is elevated (>10 U/L):
- Mycobacterial culture and sensitivity from pleural fluid (gold standard but slow, takes 2-8 weeks)
- TB PCR/nucleic acid amplification testing (NAAT) for rapid TB diagnosis
- Pleural biopsy with histopathology (for granulomas) and TB culture
- Sputum smear microscopy and culture
- Chest X-ray or CT thorax to evaluate for pulmonary TB and extent of effusion
- Tuberculin skin test (TST) or interferon-gamma release assay (IGRA)
- Pleural fluid analysis: cell count/differential, LDH, glucose, protein, pH to assess for TB characteristics
- If ADA is low (<10 U/L):
- Consider alternative diagnoses: malignancy workup with pleural fluid cytology
- BNP or NT-proBNP if heart failure suspected
- Autoimmune markers (ANA, rheumatoid factor, complement levels) if connective tissue disease suspected
- D-dimer or CT pulmonary angiography if pulmonary embolism suspected
- Monitoring frequency:
- If TB diagnosed: Clinical monitoring during anti-TB therapy (2, 4, 6, and 8 weeks initially, then every 4 weeks)
- Repeat imaging (chest X-ray) at 2-3 months to assess treatment response
- If diagnosis unclear: Repeat thoracentesis with ADA, culture, and cytology if initial results inconclusive
Fasting Required?
- Fasting required: No - this is a pleural fluid test, not a serum test; fasting is not necessary
- Sample collection procedure:
- Pleural fluid is obtained via thoracentesis (needle aspiration of pleural space under ultrasound or fluoroscopic guidance)
- Patient preparation:
- Patient should be informed about thoracentesis procedure; written consent required
- Baseline coagulation studies (PT, PTT, platelets) should be reviewed; anticoagulation may need to be held or reversed
- Aspirin and NSAIDs may be held 3-7 days before procedure; discuss with physician
- Empty bladder before procedure for comfort
- Mild sedation may be offered; remain still during needle insertion
- Special sample handling instructions:
- Pleural fluid should be collected in sterile containers; tube with EDTA for cell count, cell-free tube for ADA and biochemistry
- Samples must be handled promptly; delays >4 hours may affect results and cell viability
- Keep samples at room temperature and transport to laboratory immediately to prevent cell lysis
- If culture is needed, aseptic technique during collection is crucial
- Post-procedure instructions:
- Rest for 30 minutes to 1 hour after procedure
- Chest X-ray may be performed post-procedure to assess for pneumothorax or other complications
- Resume normal activities as tolerated; avoid strenuous activity for 24 hours
- Report signs of infection, increased shortness of breath, chest pain, or other complications to healthcare provider immediately

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