Pleural effusion laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Prince Tano Djan, BSc, MBChB [2]

Overview

Laboratory Findings

Once a pleural effusion is diagnosed, the cause must be determined. Pleural fluid is drawn out of the pleural space in a process called thoracentesis. A needle is inserted through the back of the chest wall into the pleural space. The fluid may then be evaluated for the following:

  1. Chemical composition including protein, lactate dehydrogenase (LDH), albumin, amylase, pH and glucose
  2. Gram stain and culture to identify possible bacterial infections
  3. Cell count and differential
  4. Cytology to identify cancer cells, but may also identify some infective organisms
  5. Other tests as suggested by the clinical situation - lipids, fungal culture, viral culture, specific immunoglobulins

Electrolyte and Biomarker Studies

  • Definite diagnoses can be made by specific analyses of fluid.
  • Look at the fluid- milky, bloody, clear.
  • Transudate
  • Exudates:
    • Result from pleural and lung inflammation (resulting in a capillary protein leak) or impaired lymphatic drainage of pleural space (so slow removal of protein from pleural space).
    • Can also result from movement of fluid form peritoneal space.
  • If at least one of the following 3 is present, the fluid is virtually always and exudate; in none is present, the fluid is virtually always a transudate:
    • Pleural fluid protein/serum protein ratio >0.5
    • Fluid/serum lactic dehydrogenase (LDH) ratio >0.6
    • Fluid LDH greater than 2/3 the upper limits of normal of the serum LDH
  • Some tidbits
  • Glucose
    • Lower then 60mg/dL or fluid/serum ratio < 0.5 not seen in transudates and limits exudates to the following
  • pH
    • Less than 7.30 with nrl blood pH found with same diagnosis as low glucose.
    • Normal pleural fluid is around 7.6 due to a bicarbonate gradient between pleural fluid and blood.
  • Amylase
    • Greater than the upper limit of normal for serum or a pleural fluid to serum ration >1 narrows an exudate to acute pancreatitis, chronic pancreatic effusion, esophageal rupture or malignancy.
  • C-reactive protein (CRP)

Pleural fluid CRP is superior to serum CRP in determining pleural fluid etiology. Quantitative measurement of pleural fluid CRP might be a useful complementary diagnostic and prognostic test for lung cancer patients with malignant pleural effusion.[1]

Transudate vs. Exudate

The third step in the evaluation of pleural fluid is to determine whether the effusion is a transudate or an exudate. Transudative pleural effusions are caused by systemic factors that alter the balance of the formation and absorption of pleural fluid (e.g., left ventricular failure,pulmonary embolism, and cirrhosis), while exudative pleural effusions are caused by alterations in local factors that influence the formation and absorption of pleural fluid (e.g., bacterial pneumonia, cancer, and viral infection).

Transudative and exudative pleural effusions are differentiated by comparing chemistries in the pleural fluid to those in the blood. According to ameta-analysis, exudative pleural effusions meet at least one of the following criteria [2]:

  1. Pleural fluid protein >2.9 g/dL (29 g/L)
  2. Pleural fluid cholesterol >45 mg/dL (1.16 mmol/L)
  3. Pleural fluid LDH >60 percent of upper limit for serum

Previously criteria proposed by Light for an exudative effusion are met if at least one of the following exists (Light's criteria)[3][2][4]:

  1. The ratio of pleural fluid protein to serum protein is greater than 0.5
  2. The ratio of pleural fluid LDH and serum LDH is greater than 0.6
  3. Pleural fluid LDH is more than two-thirds normal upper limit for serum

Twenty-five percent of patients with transudative pleural effusions are mistakenly identified as having exudative pleural effusions by Light's criteria. Therefore, additional testing is needed if a patient identified as having an exudative pleural effusion appears clinically to have a condition that produces a transudative effusion. In such cases albumin levels in blood and pleural fluid are measured. If the difference between the albumin levels in the blood and the pleural fluid is greater than 1.2 g/dL (12 g/L), it can be assumed that the patient has a transudative pleural effusion.

If the fluid is definitively identified as exudative, additional testing is necessary to determine the local factors causing the exudate.

Exudative Pleural Effusions

Once identified as exudative, additional evaluation is needed to determine the cause of the excess fluid, and pleural fluid amylase, glucose, and cell counts are obtained. The fluid is also sent for Gram staining and culture, and, if suspicious for tuberculosis, examination for TB markers[5] (adenosine deaminase > 45 IU/L, interferon gamma > 140 pg/mL, or positive polymerase chain reaction (PCR) for tuberculous DNA).

Pleural fluid amylase is elevated in cases of esophageal rupture, pancreatic pleural effusion, or cancer. Glucose is decreased with cancer, bacterial infections, or rheumatoid pleuritis. If cancer is suspected, the pleural fluid is sent for cytology. If cytology is negative, and cancer is still suspected, either a thoracoscopy, or needle biopsy of the pleura may be performed.

Diagnostic Criteria Laboratory tests Suggestive of Exudate
Lights Criteria Pleural fluid protein:Serum protein > 0.5
Pleural fluid LDH:Serum LDH > 0.6
Pleural fluid LDH level > 0.67 ULN
Two-test rule Pleural fluid protein level > 2.9 g/dL
Pleural fluid cholesterol level > 45 mg/dL
Three test rule Pleural fluid protein level > 2.9 g/dL
style="padding: 5px 5px; background: #F5F5F5;" Pleural fluid cholesterol level > 45 mg/dL
Pleural fluid LDH level > 0.67 ULN

References

  1. Park DS, Kim D, Hwang KE, Hwang YR, Park C, Seol CH; et al. (2013). "Diagnostic value and prognostic significance of pleural C-reactive protein in lung cancer patients with malignant pleural effusions". Yonsei Med J. 54 (2): 396–402. doi:10.3349/ymj.2013.54.2.396. PMC 3575996. PMID 23364973.
  2. 2.0 2.1 Heffner J, Brown L, Barbieri C (1997). "Diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Primary Study Investigators". Chest. 111 (4): 970–80. PMID 9106577.
  3. Light RW, Macgregor MI, Luchsinger PC, Ball WC (1972). "Pleural effusions: the diagnostic separation of transudates and exudates". Ann Intern Med. 77 (4): 507–13. PMID 4642731.
  4. Porcel JM, Peña JM, Vicente de Vera C, Esquerda A, Vives M, Light RW (2006). "Bayesian analysis using continuous likelihood ratios for identifying pleural exudates". Respir Med. 100 (11): 1960–5. doi:10.1016/j.rmed.2006.02.025. PMID 16626953.
  5. Corral-Gudino L, García-Zamalloa A, Prada-González C, Bielsa S, Alexis D, Taboada-Gómez J; et al. (2016). "Development and Validation of the COMPLES Score for Differentiating Between Tuberculous Effusions with Low Pleural pH or Glucose and Complicated Parapneumonic Effusions". Lung. 194 (5): 847–54. doi:10.1007/s00408-016-9923-y. PMID 27401009.

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