Pleural effusion: biochemical tests may have helped rule out malignancy.

Clinical bottom line (level 4)

  1. Malignancy was a common cause of pleural effusion.
  2. A low a1-antitrypsin , or complement factors C 3 and C 4 in the pleural fluid made malignancy much less likely.
Alexandrakis et al: Respiratory Medicine 1997; 91: 517-523
Expires October 2003

The study

Setting: university hospital, Greece

100 patients (aged range 32 to 92 years; median 65, 71% male) admitted with pleural effusions

Independent unblinded reference standard, applied in all patients from a consecutive appropriate spectrum.
Reference standard:
    • pleural biopsy and/or cytology
    • follow-up for at least 10 months if malignancy not found
Diagnostic test: on pleural fluid and serum:
  • ferritin
  • C 3
  • C 4
  • a1-antitrypsin
  • haptoglobin

The evidence

pre-test probability of malignant effusion: 47%, (95% CI: 37% to 57%)

diagnostic test malignant effusion non-malignant effusion LR+
(95% CI)		 post-test probability LR-
(95% CI)		 post-test probability
ferritin > 1000 ng/ml 32 20 1.8
(1.2 to 2.7) 		62% 0.51
(0.32 to 0.82) 		31%
C3 > 300 mg/dl 44 30 1.7
(1.3 to 2.1) 		59% 0.15
(0.047 to 0.46) 		12%
C4 > 700 mg/dl 47 26 2.0
(1.6 to 2.7) 		64% 0.00
(0.00 to 0.13) 		0%
a1-antitrypsin > 150 mg/dl 47 38 1.4
(1.2 to 1.7) 		55% 0.00
(0.00 to 0.086) 		0%
haptoglobin > 70 mg/dl 39 30 1.5
(1.1 to 1.9) 		57% 0.39
(0.19 to 0.79) 		26%
ferritin effusion: serum ratio > 0.6 44 43 1.2
(0.99 to 1.3) 		51% 0.34
(0.099 to 1.2) 		23%
C3 ratio > 0.5 24 18 1.5
(0.94 to 2.4) 		57% 0.74
(0.52 to 1.1) 		40%
C4 ratio> 0.3 38 24 1.8
(1.3 to 2.5) 		61% 0.35
(0.19 to 0.66) 		24%
a1-antitrypsin ratio > 0.6 39 31 1.4
(1.1 to 1.8) 		56% 0.41
(0.20 to 0.83) 		27%
haptoglobin ratio > 0.25 34 26 1.5
(1.1 to 2.0) 		57% 0.54
(0.32 to 0.92) 		33%
total 47 53

Comments

  1. Many studies have attempted to distinguish exudates from transudates but few to establish the cause on the basis of biochemical results.
  2. One of the significant problems in this field is the lack of a consistent reference standard

Citation

  1. Alexandrakis M, Coulocheri S, Kyriakou D, et al: diagnostic value of ferritin, haptoglobin, a1-antitrypsin , lactate dehydrogenase and complement factors C3 and C4 in pleural effusion differentiation. Respiratory Medicine 1997; 91: 517-523
Search Terms: pleural effusion in Cochrane
Contributor: Chris Ball and Clare Wotton, October 2000
Reviewer: Mitsuhiro Kamei

Clinical Question.
Patient pleural effusion
Intervention or Exposure biochemical factors
Outcome diagnosis of malignancy