What tests should be sent on pericardial fluid from a patient presenting with pericardial effusion?

What Tests to Send on Pericardial Fluid

Send pericardial fluid for cell count with differential, biochemical analysis (protein, LDH, glucose), cytology with tumor markers, bacterial/fungal/mycobacterial cultures (at least three sets), and PCR for tuberculosis as the core diagnostic panel. 1, 2

Essential Analyses for All Cases

Biochemical Studies

• Protein level and LDH distinguish exudates from transudates: protein >3.0 g/dL, fluid/serum protein ratio >0.5, LDH >200 mg/dL, and fluid/serum LDH ratio >0.6 indicate exudative effusion 3, 2
• Glucose measurement is critical for differentiating etiologies: purulent pericarditis shows mean pericardial:serum glucose ratio of 0.3, compared to 0.7 for tuberculous and 0.8 for neoplastic causes 3, 2
• Purulent effusions specifically have significantly lower absolute glucose levels (47.3 ± 25.3 mg/dL) versus non-infectious effusions (102.5 ± 35.6 mg/dL) 3

Cell Count and Differential

• Total white cell count with differential provides diagnostic clues: purulent effusions show mean 2.8/mL with 92% neutrophils, tuberculous show 1.7/mL with 50% neutrophils, and neoplastic show 3.3/mL with 55% neutrophils 2
• Bacterial and rheumatoid effusions have highest neutrophil proportions (78 ± 20% and 69 ± 23%), while malignant effusions and hypothyroidism show highest monocyte counts (79 ± 27% and 74 ± 26%) 3

Microbiological Testing

Bacterial and Fungal Studies

• At least three cultures for aerobic and anaerobic organisms are mandatory in all cases to exclude purulent pericarditis 3, 2
• Blood cultures must be obtained simultaneously before starting antibiotics 3, 2

Tuberculosis Testing

• Acid-fast bacilli staining and mycobacterial culture with radiometric growth detection (e.g., BACTEC-460) are essential 3, 2
• PCR for tuberculosis (Xpert MTB/RIF) is more specific (100%) than adenosine deaminase (ADA) estimation (78%) though slightly less sensitive (75% vs 83%) 3, 2
• ADA and interferon-gamma should be performed when tuberculosis is suspected: very high ADA levels have prognostic value for pericardial constriction, and low ADA with high CEA virtually excludes tuberculosis in favor of malignancy 3
• Pericardial lysozyme can provide additional diagnostic information for tuberculous pericarditis 3

Viral Studies

• PCR for cardiotropic viruses discriminates viral from autoreactive pericarditis and is more sensitive than bacterial cultures 3, 1

Cytology and Tumor Markers

Cytological Analysis

• Centrifugation and rapid cytological analysis improve diagnostic yield 2
• Cytology is essential for confirming malignant pericardial disease and has significantly higher sensitivity (84.8%) than pericardial biopsy (65.7%) 3, 4

Tumor Markers

• CEA, CA 125, CA 72-4, CA 15-3, CA 19-9, AFP, CD-30, and CD-25 should be measured when malignancy is suspected 3, 2
• Combination of epithelial membrane antigen, CEA, and vimentin immunocytochemical staining distinguishes reactive mesothelial cells from adenocarcinoma 3
• Differentiation of tuberculous versus neoplastic effusion is virtually absolute with low ADA and high CEA levels 3

Common Pitfalls and Caveats

• Lymphoma is the most commonly missed diagnosis (33.3% of false-negative cytology cases), so consider immunohistochemistry studies when underlying malignancy is present 4
• Fibrinous pericarditis can obscure neoplastic cells on the pericardial surface, leading to false-negative cytology 4
• Malignant effusions with negative cytology in early pericardiocentesis usually become positive over time with repeat sampling 3
• PCR analyses have higher specificity than ADA estimation for tuberculous pericarditis, making them preferable when available 3
• The pericardial drain should be left in place for 3-5 days after pericardiocentesis, with surgical pericardial window considered if drainage remains high at 6-7 days 3