What tests are ordered on a pleural fluid specimen?

From the Guidelines

Pleural fluid specimens should be sent for cytological analysis, including cell count with differential, protein, lactate dehydrogenase (LDH), glucose, pH, Gram stain, culture, and adenosine deaminase (ADA), to guide diagnosis and management of the underlying condition causing the pleural effusion. When ordering tests on pleural fluid specimens, the following should be considered:

• Cytology is important for detecting malignant cells, with higher yield when multiple samples are analyzed 1
• Microbiological tests, including acid-fast bacilli smear and culture for tuberculosis, are crucial when infection is suspected 1
• Pleural fluid biomarkers, such as adenosine deaminase (ADA) and interferon gamma (IFN-gamma), can be considered for diagnosing tuberculous pleural effusion in high prevalence populations 1
• Tissue sampling for culture and sensitivity should be the preferred option for all patients with suspected tuberculous pleural effusion 1
• Additional tests, such as amylase, triglycerides, NT-proBNP, and tumor markers, may be considered based on the clinical context and suspected underlying condition 1 The British Thoracic Society guideline for pleural disease recommends that 25-50 mL of pleural fluid should be submitted for cytological analysis in patients with suspected malignant pleural effusion (MPE) 1, and that pleural fluid should be sent in both plain and blood culture bottle tubes in patients with suspected pleural infection 1. In terms of specific tests, pleural fluid cytology should be used as an initial diagnostic test in patients with suspected secondary pleural malignancy 1, and tissue sampling for culture and sensitivity should be the preferred option for all patients with suspected tuberculous pleural effusion 1. Overall, the choice of tests will depend on the clinical context and suspected underlying condition, and should be guided by the most recent and highest quality evidence available 1.

From the Research

Tests Ordered on Pleural Fluid Specimen

• The following tests are commonly ordered on a pleural fluid specimen to aid in diagnosis and management:
  • Cell count and differential 2
  • Tests for protein, LDH, glucose, adenosine deaminase, cytology 2
  • pH and bacterial and mycobacterial cultures if infection is a concern 2
  • Gram stain and cultures, glucose, amylase, lactic acid dehydrogenase, cytology, and a marker for tuberculous pleuritis for exudative pleural fluids 3
• Light's criteria are used to differentiate transudative from exudative effusion, and additional tests are indicated to determine the etiology of the effusion if it is exudative 4
• Pleural fluid C-reactive protein (CRP) levels can be used as an additional tool in the differential diagnosis of exudative effusion, and can help differentiate parapneumonic effusion and empyema from tuberculous and malignant effusions 5

Specific Tests for Certain Conditions

• Adenosine deaminase levels >35 IU/L usually indicate tuberculosis in lymphocyte-predominant pleural fluid 2
• Adenosine deaminase levels >45 IU/L or a gamma interferon level >3.7 U/ml are suggestive of tuberculous pleuritis 3
• pH < 7.2 or glucose < 60 mg/dL allow the clinician to identify complicated parapneumonic effusions 2
• Conventional cytology may reveal malignant cells in 60% of patients with malignant effusions 2
• Natriuretic peptide assays can improve the accuracy of a diagnosis of cardiac pleural effusion 2
• Pleural fluid mesothelin levels > 20 nmol/L are highly suggestive of mesothelioma 2