Body Fluid Reference Intervals and/or Interpretive Information for Select Analytes

  Biliary/Hepatic CSF Dialysate Drain Pancreatic Pericardial Peritoneal/Ascites Pleural Synovial Vitreous
Amylase            
Bilirubin (Total)            
CA 19-9          
Carcinoembryonic Antigen (CEA)          
Cholesterol            
Chloride (Cl⁻)        
Glucose        
Lactate Dehydrogenase (LDH)          
Lipase      
Potassium (K⁺)        
Protein (Total)          
Rheumatoid Factor (RF)            
Sodium (Na⁺)        
Triglycerides            
Uric Acid            

This website provides reference intervals and/or interpretive guidance when testing for common and esoteric analytes in body fluids. The information was assimilated from an extensive literature search of studies (eg, meta-analysis), guidelines, and key textbooks related to the interpretation of body fluid testing. This information should not be considered all-inclusive or applicable to all clinical scenarios.

For each analyte, separate entries for individual body fluids are included. Each body fluid entry contains clinical indications, reference intervals and/or interpretive information, and literature references. References have PMID numbers, which provide quick access to the various source materials in PubMed. Information should be interpreted with caution and in the context of the instrumentation used because the literature sources consist of studies across many decades, analyzers, and reagent formulations. All information should be viewed in the context of the patient’s clinical presentation. Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence.

This website will be updated with additional assays, reference intervals and interpretive guidance, and references as information becomes available. In addition to the separate analyte entries, Suggested References provides additional resources which may assist with body fluid validations and additional clinical information.


Amylase

Drain

Clinical Indications

Evaluation of potential pancreatic fistula

Supportive evidence for source of fluid accumulation

Reference Interval and/or Interpretive Information

Drain fluid amylase should be interpreted in the context of source and in correlation with serum results and/or other clinical evidence.

After pancreaticoduodenectomy, postoperative pancreatic fistula has been defined by the International Study Group on Pancreatic Fistula Definition (ISGPF) as “a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content greater than 3 times the serum amylase activity.” [1]

References

[1] Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, Sarr M, Taverso W, Buchler M, for the International Study Group on Pancreatic Fistula. 2005. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 138(1):8-13. PMID: 16003309.

Pancreatic

Clinical Indications

Supportive evidence in the differentiation of pancreatic cysts from pseudocysts

Reference Interval and/or Interpretive Information

In the context of pancreatic cyst versus pseudocyst differentiation, a pancreatic fluid amylase activity <250 U/L (the upper limit of the normal serum value for amylase in a meta-analysis) is evidence against the possibility that the fluid collection represents a pseudocyst. [1]

References

[1] Van der Waaij LA, van Dullemen HM, Porte RJ. 2005. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointestinal Endoscopy. 62(3):383-389. PMID: 16111956.

Peritoneal/Ascites

Clinical Indications

Evaluation of pancreatic ascites

Reference Interval and/or Interpretive Information

In normal peritoneal fluid, amylase activity is comparable to that observed in serum or plasma. [1,2]

Pancreatic ascites may be associated with peritoneal amylase activity 3-5x greater than a corresponding serum or plasma level. [1,2,3]

Routine analysis of peritoneal fluid amylase activity is usually not clinically indicated. [1]

References

[1] Kjeldsberg CR, Straseski JA, Couturier MR, Cohen MB. Chapter 6: Peritoneal fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds.  ASCP Press: Chicago, IL, 2015. ISBN 978-089189-5824.

[2] Runyon BA. 1987. Amylase levels in ascitic fluid. J Clin Gastroenterol. 9(2): 172-174. PMID: 2437177.

[3] Block DR, Franke DDH. Quick Guide to Body Fluid Testing. AACC Press (Washington, DC), 2015. ISBN 978-1-59425-180-1.

Pleural

Clinical Indications

Routine analysis of pleural fluid amylase activity with pleural effusion is usually not clinically indicated [1,2]

Use has been suggested when there is an elevated pretest probability of acute pancreatitis, chronic pancreatic disease, or esophageal rupture [2]

May also provide supportive evidence in the evaluation of suspected pancreatic-pleural fistula [3]

Reference Interval and/or Interpretive Information

Elevated pleural fluid amylase activity is a level greater than the upper reference limit for serum and a fluid-to-serum amylase ratio of >1. [4]

While high pleural amylase levels have also been associated with some malignancy-related pleural effusions (such as adenocarcinoma) in some reports [5,6,7], use for such evaluations is generally not suggested (due to specificity concerns) and would be considered secondary to more specific methods such as cytology.

References

[1] Kjeldsberg CR, Grenache DG, Couturier MR, Cohen MB. Chapter 5: Pleural and pericardial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN 978-089189-5824.

[2] Branca P, Rodriguez RM, Rogers JT, Ayo DS, Moyers JP, Light RW. 2001. Routine measurement of pleural fluid amylase is not indicated. Arch Intern Med. 161(2):228-232. PMID: 11176736.

[3] Elkaoui H, Atoini F, Bouchentouf SM, El Omari F, Mahi M, Ait Ali A, Bounaim A, Sair K, Zentar A. 2012. Pancreatic-pleural fistula in chronic pancreatitis. Arab J Gastroenterol. 13(1):38-40. PMID: 22560825.

[4] Sahn SA. 2012. Getting the most from pleural fluid analysis. Respirology. 17: 270-277. PMID: 22059482.

[5] CLSI. Analysis of Body Fluids in Clinical Chemistry; Approved Guideline. CLSI document C49-A. Wayne, PA:  Clinical and Laboratory Standards Institute; 2007.

[6] Kramer MR, Saldana MJ, Cepero RJ, Petchenik AE. 1989. High amylase levels in neoplasm-related pleural effusion. Annals of Internal Medicine. 110:567-69. PMID: 2466431.

[7] Villena V, Pérez V, Pozo F, López-Encuentra A, Echave-Sustaeta J, Arenas J, Escribano PM. 2002. Amylase levels in pleural effusions: a consecutive unselected series of 841 patients. CHEST. 121(2):470-474. PMID: 11834659.

Bilirubin (Total)

Biliary/Hepatic

Clinical Indications

Supportive evidence for biliary and/or hepatic source of fluid accumulation

Identification of bile leakage

Reference Interval and/or Interpretive Information

After hepatobiliary and/or pancreatic surgery, bile leakage has been defined by the International Study Group of Liver Surgery as “bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis.” [1]

In Jackson Pratt (JP) drain fluid, one study has demonstrated that a drain fluid bilirubin of 4.9 mg/dL or greater (or a drain fluid-to-serum bilirubin ratio of 5.4 or greater) had a 100% sensitivity and specificity for the identification of bile leaks. [2]

References

[1] Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras JF, DeMatteo RP, Büchler MW, Weitz J. 2011. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 149(5):680-688. PMID: 21316725.

[2] Darwin P, Goldberg E, Uradomo L. 2010. Jackson Pratt drain fluid-to-serum bilirubin concentration ratio for the diagnosis of bile leaks. Gastrointestinal Endoscopy. 71(1):99-104. PMID: 19945100.

Drain

Clinical Indications

Identification of bile leakage

Reference Interval and/or Interpretive Information

After hepatobiliary and/or pancreatic surgery, bile leakage has been defined by the International Study Group of Liver Surgery as “bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis.” [1]

In Jackson Pratt (JP) drain fluid, one study has demonstrated that a drain fluid bilirubin of 4.9 mg/dL or greater (or a drain fluid-to-serum bilirubin ratio of 5.4 or greater) had a 100% sensitivity and specificity for the identification of bile leaks. [2]

References

[1] Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras JF, DeMatteo RP, Büchler MW, Weitz J. 2011. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 149(5):680-688. PMID: 21316725.

[2] Darwin P, Goldberg E, Uradomo L. 2010. Jackson Pratt drain fluid-to-serum bilirubin concentration ratio for the diagnosis of bile leaks. Gastrointestinal Endoscopy. 71(1):99-104. PMID: 19945100.

Peritoneal/Ascites

Clinical Indications

Supportive evidence for differentiation of exudates and transudates

Identification of choleperitoneum

Identification of bile leakage

Reference Interval and/or Interpretive Information

As supportive evidence to Light’s criteria for the differentiation of exudates from transudates, an ascites fluid-to-serum bilirubin ratio of 0.6 may be consistent with the presence of an exudate. [1]

An ascites fluid bilirubin concentration >6 mg/dL with an ascites fluid-to-serum bilirubin ratio of >1 has been observed in choleperitoneum associated with gallbladder rupture. [2; based on a single case]

After hepatobiliary and/or pancreatic surgery, bile leakage has been defined by the International Study Group of Liver Surgery as “bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis.” [3]

In Jackson Pratt (JP) drain fluid, one study has demonstrated that a drain fluid bilirubin of 4.9 mg/dL or greater (or a drain fluid-to-serum bilirubin ratio of 5.4 or greater) had a 100% sensitivity and specificity for the identification of bile leaks. [4]

References

[1] Elis et al. 1998. Ascitic fluid-to-serum bilirubin concentration ratio for the classification of transudates or exudates. Am J Gastroenterol. 93(3):401-3. PMID: 9517648.

[2] Runyon BA. 1987. Ascitic fluid bilirubin concentration as a key to choleperitoneum. J Clin Gastroenterol. 9(5):543-5. PMID: 3680904.

[3] Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras JF, DeMatteo RP, Büchler MW, Weitz J. 2011. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 149(5):680-688. PMID: 21316725.

[4] Darwin P, Goldberg E, Uradomo L. 2010. Jackson Pratt drain fluid-to-serum bilirubin concentration ratio for the diagnosis of bile leaks. Gastrointestinal Endoscopy. 71(1):99-104. PMID: 19945100.

Pleural

Clinical Indications

Supportive evidence for differentiation of exudates and transudates

Reference Interval and/or Interpretive Information

As supportive evidence to Light’s criteria for the differentiation of exudates from transudates, a pleural fluid-to-serum bilirubin concentration ratio of 0.6 may be consistent with the presence of an exudate. [1]

References

[1] Meisel S, Shamiss A, Thaler M, Nussinovitch N, Rosenthal T. 1990. Pleural fluid-to-serum bilirubin concentration ratio for the separation of transudates from exudates. CHEST. 98(1):141-144. PMID: 2361381.

CA 19-9

Biliary/Hepatic

Clinical Indications

Supportive evidence in the evaluation of suspected malignancy

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

Hepatic / biliary cyst fluid CA 19-9 may be elevated in non-malignant (simple hepatic cysts, polycystic liver disease), pre-malignant (biliary cystadenomas), and malignant (biliary cystadenocarciomas) conditions. [1,2,3]

While statistical differences have been observed between groups of benign (hepatic simple cysts) versus mucinous (biliary cystadenomas, biliary cystadenocarcinoma, intraductal papillary mucinous neoplasm) cysts in one study, high intra-group variability has prevented the establishment of clinically-useful cutoffs. [2]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Choi JK, Lee JK, Lee KH, Lee KT, Rhee JC, Kim KH, Jang KT, Kim SH, Park Y. 2010. Differential diagnosis for intrahepatic biliary cystadenoma and hepatic simple cyst. J. Clin Gastroenterol. 44:289-293. PMID: 19770676.

[2] Fuks D, Voitot J, Paradis V, Belghiti J, Vilgrain V, Farges O. 2014. Intracystic concentrations of tumor markers for the diagnosis of cystic liver lesions. Br J Surg. 101:408-416. PMID: 24477793.

[3] Waanders E, van Keimpema L, Brouwer JT, van Oijen MGH, Aerts R, Sweep FCGJ, Nevens F, Drenth JPH. 2009. Carbohydrate antigen 19-9 is extremely elevated in polycystic liver disease. Liver International. 29(9):1389-95. PMID: 19515221.

ARUP Assay:  Roche cobas e602 Carbohydrate Antigen (CA 19-9)

CSF

Clinical Indications

Supportive evidence in the evaluation of suspected leptomeningeal carcinomatosis

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

Elevations in cerebrospinal fluid (CSF) CA 19-9 have been shown in certain cases of leptomeningeal carcinomatosis. [1,2,3]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Kosmas C, Tsavaris NB, Tsakonas G, Soukouli G, Gassiamis A, Mylonakis N, Karabelis A. 2005. Cerebrospinal fluid tumor marker levels in predicting response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer. Med Sci Monit. 11(8):CR398-401. PMID: 16049383.

[2] Sato Y, Ohta Y, Kaji M, Oizumi K, Kaji M. 1998. Carbohydrate antigen 19-9 in cerebrospinal fluid and within malignant cells in a case of leptomeningeal carcinomatosis. J Neurol Neurosurg Psychiatry. 65:402-403. PMID: 9728963.

[3] Yasumoto K, Takahashi Y, Mai M, Kawashima A. 2005. Meningeal carcinomatosis preceded by a rapid increase in serum CA 19-9 levels in a patient with breast cancer. Int J Clin Oncol. 10(4):276-80. PMID: 16136375.

ARUP Assay:  Roche cobas e602 Carbohydrate Antigen (CA 19-9)

Pancreatic

Clinical Indications

Supportive evidence in evaluation of pancreatic cystic lesions

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

A pooled analysis of 12 studies investigating pancreatic cyst fluid found that a CA19-9 of <37 U/mL (the upper limit of a normal serum CA 19-9 value) had a sensitivity of 19% and a specificity of 98% in differentiating serous cystadenomas and pseudocysts from mucinous cystadenomas and/or mucinous cystadenocarcinomas. [1]

A 2004 multicenter study, however, found that CA19-9 did not perform as well as CEA in differentiating between mucinous and non-mucinous lesions. [2]

A separate study has suggested that high CA 19-9 (>8000 U/L; as one component of a testing and interpretation algorithm) can help to differentiate mucinous cystadenomas from intraductal papillary mucinous neoplasms (IPMN). [3]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Van der Waaij LA, van Dullemen HM, Porte RJ. 2005. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointestinal Endoscopy. 62(3):383-389. PMID: 16111956.

[2] Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL, and the Investigators of the CPC Study. 2004. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 126:1330-1336. PMID: 15131794.

[3] Snozek CLH, Mascarenhas RC, O’Kane DJ. 2009. Use of cyst fluid CEA, CA19-9, and amylase for evaluation of pancreatic lesions. Clinical Biochemistry. 24:1585-1588. PMID: 19576876.

ARUP Assay:  Roche cobas e602 Carbohydrate Antigen (CA 19-9)

Peritoneal/Ascites

Clinical Indications

Supportive evidence in evaluation of suspected malignant ascites

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

An ascites fluid CA 19-9 (at a diagnostic cutoff of 72 U/mL) showed a 30% sensitivity and 95% specificity for the differentiation of malignant from non-malignant ascites. [1; DXI method]

Elevated concentrations of ascites fluid CA 19-9 were observed in malignancies which are known to elevate CA 19-9 in the serum. [1]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Kaleta EJ, Tolan NV, Ness KA, O’Kane DO, Algeciras-Schimnich A. 2013. CEA, AFP, and CA 19-9 analysis in peritoneal fluid to differentiate causes of ascites formation. Clinical Biochemistry. 46:814-818. PMID: 23454391.

ARUP Assay:  Roche cobas e602 Carbohydrate Antigen (CA 19-9)

Pleural

Clinical Indications

Supportive evidence in evaluation of suspected malignant pleural effusion

Meta-analyses do not support the routine use of single tumor markers for the diagnosis of malignant pleural effusions [1,2]

British Thoracic Society 2010 pleural disease guideline states that pleural fluid tumor markers do not have a role in the routine analysis of pleural effusions [3]

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

At a CA19-9 cutoff of ≥20 U/mL, one report demonstrated a 35% sensitivity and a 95% specificity for detection of malignant pleural effusions. [4]

In that report CA19-9 concentrations were typically not elevated when the effusion was due to malignancies that are not associated with serum elevations of CA19-9. [4]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Liang QL, Shi HZ, Qin XJ, Liang XD, Yang HB. 2008. Diagnostic accuracy of tumour markers for malignant pleural effusion: a meta analysis. Thorax. 63:35-41. PMID: 17573438.

[2] Nguyen AH, Miller EJ, Wichman CS, Berim IG, Agrawal DK. 2015. Diagnostic value of tumor antigens in malignant pleural effusion: a meta-analysis. Translational Research. Epub ahead of print. PMID: 25953662.

[3] Hooper C, Lee YCG, Maskell N, on behalf of the BTS Pleural Guideline Group. 2010. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax. 65(Suppl 2):ii4-ii17. PMID: 20696692.

[4] Hackbarth JS, Murata K, Reilly WM, Algeciras-Schimnich A. 2010. Performance of CEA and CA19-9 in identifying pleural effusions caused by specific malignancies. Clinical Biochemistry. 43:1051-1055. PMID: 20529669.

ARUP Assay:  Roche cobas e602 Carbohydrate Antigen (CA 19-9)

Carcinoembryonic Antigen (CEA)

CSF

Clinical Indications

Supportive evidence in the evaluation of suspected leptomeningeal carcinomatosis

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

Elevations in cerebrospinal fluid (CSF) carcinoembryonic antigen (CEA) have been shown in certain cases of leptomeningeal carcinomatosis. [1,2,3,4]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Corsini E, Bernardi G, Gaviani P, Silvani A, de Grazia U, Ciusani E, Croci D, Salmaggi A. 2009. Intrathecal synthesis of tumor markers is a highly sensitive test in the diagnosis of leptomeningeal metastasis from solid cancers. Clin Chem Lab Med. 47(7):874-879. PMID: 19453289.

[2] Klee GG, Tallman RD, Goellner JR, Yanagihara T. 1986. Elevation of carcinoembryonic antigen in cerebrospinal fluid among patients with meningeal carcinomatosis. Mayo Clin Proc. 61(1):9-13. PMID: 3510343.

[3] Nakagawa H, Kubo S, Murasawa A, Nakajima S, Nakajima Y, Izumoto S, Hayakawa T. 1992. Measurements of CSF biochemical tumor markers in patients with meningeal carcinomatosis and brain tumors. J Neurooncol. 12(2):111-20. PMID: 1560255.

[4] Yap BS, Yap HY, Fritsche HA, Blumenschein G, Bodey GP. 1980. CSF Carcinoembryonic antigen in meningeal carcinomatosis from breast cancer.  JAMA. 244(14):1601-1603. PMID: 7420663.

ARUP Assay:  Roche cobas e602 Carcinoembryonic Antigen (CEA)

Pancreatic

Clinical Indications

Supportive evidence in evaluation of pancreatic cystic lesions

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

A pooled analysis of 12 studies investigating pancreatic cyst fluid found that a CEA of >800 ng/mL had a sensitivity of 48% and a specificity of 98% in distinguishing mucinous cystadenoma and mucinous cystadenocarcinoma from serous cystadenoma and pseudocyst. [1]

A CEA <5 ng/mL was 54% sensitive and 94% specific for identifying serous cystadenoma and/or pseudocyst. [1]

In a review of 124 pancreatic cyst fluids (with histologic confirmation), a CEA level ≥ 200 ng/mL had a sensitivity of 60% and a specificity of 93% for identifying mucinous pancreatic lesions. [2]

CEA levels did not differentiate benign from malignant mucinous cysts. [2]

A separate 2004 multicenter study found that CEA (at a 192 ng/mL cutoff) had a 73% sensitivity and 84% specificity in differentiating between mucinous and non-mucinous lesions. [3]

A 2009 study used a CEA cutoff of >30 ng/mL (as one component of a testing and interpretation algorithm) to help differentiate mucinous from non-mucinous cysts. [4]

A wide range of within-group CEA concentrations was noted.

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Van der Waaij LA, van Dullemen HM, Porte RJ. 2005. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointestinal Endoscopy. 62(3):383-389. PMID: 16111956.

[2] Park WG, Mascarenhas R, Palaez-Luna M, Smyrk TC, O’Kane D, Clain JE, Levy MJ, Pearson RK, Petersen BT, Topazian MD, Vege SS, Chari ST. 2011. Diagnostic performance of cyst fluid carcinoembryonic antigen and amylase in histologically confirmed pancreatic cysts. Pancreas. 40(1):42-45. PMID: 20966811.

[3] Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan S, del Castillo CF, Warshaw AL, and the Investigators of the CPC Study. 2004. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 126:1330-1336. PMID: 15131794.

[4] Snozek CLH, Mascarenhas RC, O’Kane DJ. 2009. Use of cyst fluid CEA, CA19-9, and amylase for evaluation of pancreatic lesions. Clinical Biochemistry. 24:1585-1588. PMID: 19576876.

ARUP Assay:  Roche cobas e602 Carcinoembryonic Antigen (CEA)

Pericardial

Clinical Indications

Supportive evidence in the evaluation of suspected malignant pericarditis

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

Elevations in CEA have been observed in certain cases of malignant pericarditis. [1,2,3]

While limited data is available, one study of 36 patients reported that a pericardial fluid CEA cutoff >5 ng/mL had a sensitivity of 73% and a specificity of 90% for the recognition of malignant pericarditis. [1]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Szturmowicz M, Tomkowski W, Fijalkowska A, Burakowski J, Sakowicz A, Filipecki S. 1997. The role of carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) evaluation in pericardial fluid for the recognition of malignant pericarditis. Int J Biol Markers. 12(3):96-101. PMID: 9479590.

[2] Szturmowicz M, Tomkowski W, Fijalkowska A, Kupis W, Cieslik A, Demkow U, Langfort R, Wiechecka A, Orlowshi T, Torbicki A. 2005. Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis. Int J Biol Markers. 20(1):43-9. PMID: 15832772.

[3] Tatsuta M, Yamamura H, Yamamoto R, Ichii M, Iishi H, Noguchi S. 1984. Carcinoembryonic antigens in the pericardial fluid of patients with malignant pericarditis. Oncology. 41(5):328-30. PMID: 6472769.

ARUP Assay:  Roche cobas e602 Carcinoembryonic Antigen (CEA)

Peritoneal/Ascites

Clinical Indications

Supportive evidence in evaluation of suspected malignant ascites

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

An ascites fluid CEA (at a cutoff of 3.5 ng/mL) showed a 31% sensitivity and 95% specificity for the differentiation of malignant from non-malignant ascites in one report. [1]

Higher concentrations of ascites fluid CEA were observed in malignancies which are known to elevate CEA in the serum. [1]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Kaleta EJ, Tolan NV, Ness KA, O’Kane DO, Algeciras-Schimnich A. 2013. CEA, AFP, and CA 19-9 analysis in peritoneal fluid to differentiate causes of ascites formation. Clinical Biochemistry. 46:814-818. PMID: 23454391.

ARUP Assay:  Roche cobas e602 Carcinoembryonic Antigen (CEA)

Pleural

Clinical Indications

Supportive evidence in evaluation of suspected malignant pleural effusion

Meta-analyses do not support the routine use of single tumor markers for the diagnosis of malignant pleural effusions [1,2]

British Thoracic Society 2010 pleural disease guideline states that pleural fluid tumor markers do not have a role in the routine analysis of pleural effusions [3]

Body fluid tumor markers should NOT be used as sole evidence of malignancy for diagnostic purposes and should be reviewed in correlation with cytology, serum results, and other clinical evidence. Results should be interpreted with caution when considering literature-based sources of interpretive guidance, as alternative assays and/or instruments are frequently used between studies.

Reference Interval and/or Interpretive Information

A CEA cutoff of ≥3.5 ng/mL demonstrated a 52% sensitivity and 96% specificity for detection of malignant pleural effusions in one report. [4]

In that report CEA concentrations were typically not elevated when the effusion was due to malignancies that are not associated with serum elevations of CEA. [4]

Results should be reviewed in correlation with cytology, serum results, and other clinical evidence.

References

[1] Liang QL, Shi HZ, Qin XJ, Liang XD, Yang HB. 2008. Diagnostic accuracy of tumour markers for malignant pleural effusion: a meta analysis. Thorax. 63:35-41. PMID: 17573438.

[2] Nguyen AH, Miller EJ, Wichman CS, Berim IG, Agrawal DK. 2015. Diagnostic value of tumor antigens in malignant pleural effusion: a meta-analysis. Translational Research. Epub ahead of print. PMID: 25953662.

[3] Hooper C, Lee YCG, Maskell N, on behalf of the BTS Pleural Guideline Group. 2010. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax. 65(Suppl 2):ii4-ii17. PMID: 20696692.

[4] Hackbarth JS, Murata K, Reilly WM, Algeciras-Schimnich A. 2010. Performance of CEA and CA19-9 in identifying pleural effusions caused by specific malignancies. Clinical Biochemistry. 43:1051-1055. PMID: 20529669.

ARUP Assay:  Roche cobas e602 Carcinoembryonic Antigen (CEA)

Cholesterol

Drain

Clinical Indications

See Clinical Indications for individual source fluid types

Reference Interval and/or Interpretive Information

Drain fluid cholesterol should be interpreted in the context of source (e.g., pleural, peritoneal, etc.) and in correlation with serum results and/or other clinical evidence.

References

None listed.

Pericardial

Clinical Indications

Evaluation of cholesterol pericarditis

Supportive evidence for differentiation of exudates and transudates

Reference Interval and/or Interpretive Information

Elevations in pericardial cholesterol are observed in cholesterol pericarditis. [1,2,3]

In a study of 30 patients undergoing elective open heart surgery (without evidence of pericardial disease), the “normal” pericardial fluid mean cholesterol value was 43 mg/dL (99% confidence interval, 29-58 mg/dL). [4]

This was also expressed as a “normal” mean fluid-to-serum cholesterol ratio of 0.3 (99% confidence interval, 0.2-0.4). [4]

Pericardial cholesterol may also be useful in the differentiation of exudates from transudates. [5]

References

[1] Raposo L, Andrade J, Ferreira J, Aguiar C, Abecasis M, Ramos S, Reis AB, Martins AP, Pais MJ, Gomes RS. 2005. Cholesterol pericarditis – relapsing pericardial effusion in a patient with rheumatoid arthritis. Rev Port Cardiol. 24:737-45. PMID: 16041969.

[2] Barcin CB, Yalcinkaya E, Kabul HK. 2013. Cholesterol pericarditis associated with rheumatoid arthritis: a rare cause of pericardial effusion. International Journal of Cardiology. 166:e56-e58. PMID: 23410494.

[3] Setty NS, Sadananda KS, Nanjappa MC, Patra S, Basappa H, Krishnappa S. 2014. Massive pericardial effusion and cardiac tamponade due to cholesterol pericarditis in a case of subclinical hypothyroidism: a rare event. J Am Coll Cardiol. 63(14):1451. PMID: 24561150.

[4] Ben-Horin S, Shinfeld A, Kachel E, Chetrit A, Livneh A. 2005. The composition of normal pericardial fluid and its implications for diagnosing pericardial effusions. The American Journal of Medicine. 118:636-640. PMID: 15922695.

[5] Burgess LJ, Reuter H, Taljaard JJF, Doubell AF. 2002. Role of biochemical tests in the diagnosis of large pericardial effusions. CHEST. 121(2):495-499. PMID: 11834663.

Peritoneal/Ascites

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Studies have suggested that ascites fluid cholesterol (using a cutoff of 48 mg/dL) may provide supportive evidence when attempting to differentiate malignant from cirrhotic ascites. [1,2]

Such use, however, is limited by lack of specificity and is not recommended. [3,4]

The American Association for the Study of Liver Disease practice guideline, Management of Adult Patients with Ascites Due to Cirrhosis (Update 2012), lists ascitic fluid cholesterol as “unhelpful”. [5]

References

[1] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[2] Kjeldsberg CR, Straseski JA, Couturier MR, Cohen MB. Chapter 6: Peritoneal fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[3] Runyon BA. 1986. Ascitic fluid “humoral tests of malignancy.” Hepatology. 6(6):1443-1445. PMID: 3793018.

[4] Runyon BA. 1994. Editorial: Malignancy-related ascites and ascitic fluid “humoral tests of malignancy.” J Clin Gastroenterol.18(2):94-8. PMID: 8189030.

[ 5] Runyon BA. 2012. Practice Guideline. Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. American Association for the Study of Liver Diseases. http://www.aasld.org/sites/default/files/guideline_documents/adultascitesenhanced.pdf.

Pleural

Clinical Indications

Supportive evidence for differentiation of exudates and transudates

Differentiating chylothorax from pseudochylothorax

Reference Interval and/or Interpretive Information

As supportive evidence to Light’s criteria, fluid cholesterol may provide additional evidence in differentiating exudates (>45 mg/dL) from transudates (≤45 mg/dL). [1,2,3]

This may also be expressed in terms of a pleural fluid-to-serum cholesterol ratio with ≥0.3 often associated with exudates and <0.3 often associated with transudates. [3,4]

Pleural fluid cholesterol can also be used along with triglycerides to help distinguish chylothorax (triglycerides >110 mg/dL, cholesterol <200 mg/dL) from pseudochylothorax (triglycerides <50 mg/dL, cholesterol >200 mg/dL). [5,6,7,8]

References

[1] Costa M, Quiroga T, Cruz E. 1995. Measurement of pleural fluid cholesterol and lactate dehydrogenase. A simple and accurate set of indicators for separating exudates from transudates. Chest. 1108(5):1260-3. PMID: 7587426.

[2] CLSI. Analysis of Body Fluids in Clinical Chemistry; Approved Guideline. CLSI document C49-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2007.

[3] Kjeldsberg CR, Grenache DG, Couturier MR, Cohen MB. Chapter 5: Pleural and pericardial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[4] Valdés L, Pose A, Suàrez J, Gonzalez-Juanatey JR, Sarandeses A, San José E, Alvarez Dobaña JM, Salgueiro M, Rodríguez Suárez JR. 1991. Cholesterol: a useful parameter for distinguishing between pleural exudates and transudates. Chest. 99(5):1097-102. PMID: 2019164.

[5] Hillerdal G. 1997. Chylothroax and pseudochylothroax. Eur Respir J. 10(5):1157-62. PMID: 9163662.

[6] McGrath EE, Blades Z, Anderson PB. 2009. A systematic approach to the investigation and diagnosis of a unilateral pleural effusion. Int J Clin Pract. 63(11):1653-9. PMID: 19765100.

[7] McGrath EE, Blades Z, Anderson PB. 2010. Chylothorax: aetiology, diagnosis, and therapeutic options. Respiratory Medicine. 104:1-8. PMID: 19766473.

[8] Staats BA, Ellefson RD, Budahn LL, Dines DE, Prakash UB, Offord K. 1980. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc. 55(11):700-704. PMID: 7442324.

Chloride (Cl⁻)

CSF

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Infants: 110-130 mmol/L [1]

Adults: 118-132 mmol/L [1]

CSF chloride levels are expected to increase and/or decrease with conditions which increase and/or decrease serum chloride levels.

CSF chloride is not recommended for the routine evaluation of suspected tuberculous meningitis. [2]

References

[1] Tietz Clinical Guide to Laboratory Tests. 2006. 4th Ed. AHB Wu, Ed. Saunders Elsevier, St. Louis, MO. ISBN: 978-0-7216-7375-4.

[2] Schoel EJ. 1984. Spinal fluid chloride: a test 40 years past its prime. JAMA. 251(1):37-38. PMID: 6690762.

Drain

Clinical Indications

See Clinical Indications for individual source fluid types

Reference Interval and/or Interpretive Information

Drain fluid chloride (Cl-) should be interpreted in the context of source and in correlation with serum results and/or other clinical evidence.

References

None listed.

Pancreatic

Clinical Indications

Pancreatic function testing

Reference Interval and/or Interpretive Information

Studies from healthy subjects undergoing endoscopic pancreatic function testing noted that the concentration of chloride (Cl-) in pancreatic fluid secretions decrease after stimulation. [1]

A mean Cl- nadir of 44 mmol/L ± 14 SD after stimulation was observed in one study of 28 subjects. [2]

As this decrease in chloride after stimulation is inverse of the pattern observed when looking at peak bicarbonate (HCO3-) levels during endoscopic pancreatic function testing, Cl- has been suggested by one group as a potentially useful surrogate due to analyte (HCO3-) instability issues. [2]

Pancreatic fluid Cl- secretions are also decreased in cystic fibrosis. [3]

References

[1] Stevens T, Conwell DL, Zuccaro G, Van Lente F, Khandwala F, Purich E, Vargo JJ, Fein S, Dumot JA, Trolli R, O’Laughlin CO. 2004. Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects. Gastrointestinal Endoscopy. 60(3):351-355. PMID: 15332022.

[2] Wu BU, Purich ZG, Banks PA, Conwell DL. 2008. Reference values for bicarbonate and chloride secretion in endoscopically collected pancreatic fluid among healthy volunteers. Pancreas. 37(4):502. [Abstracts of Papers Submitted to the 39th Annual Meeting of the American Pancreatic Association, November 7-8, 2008, Chicago, Illinois].

[3] Kopelman H, Corey M, Gaskin K, Durie P, Weizman Z, Forstner G. 1988. Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas. Gastroenterology. 95(2):349-55. PMID: 3391365.

Pericardial

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Pericardial fluid chloride (Cl-) levels are similar to those observed in blood. [1]

References

[1] Hutchin P, Nino HV, Suberman R. 1971. Electrolyte and acid-base composition of pericardial fluid in man. Arch Surg. 102:28-30. PMID: 5538765.

Peritoneal/Ascites

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

While limited published data is available on peritoneal electrolytes in healthy individuals, pericardial fluid chloride (Cl-) levels have been shown to correlate with venous plasma levels in one study of cirrhotic patients. [1]

Results should be interpreted with caution in specimens from patients undergoing peritoneal dialysis.

References

[1] Nguyen-Krac E, Thevenot T, Capron D, Dharancy S, Paupart T, Thabut D, Tiry C. 2008. Are ascitic electrolytes usable in cirrhotic patients?  Correlation of sodium, potassium, chloride, urea, and creatinine concentration in ascitic fluid and blood. Eur J Intern Med. PMID: 19046728.

Pleural

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Limited published data exists regarding “normal” pleural fluid electrolytes.

References

None listed.

Glucose

CSF

Clinical Indications

Supportive information for the differentiation of bacterial, fungal, and viral CNS infection

Reference Interval and/or Interpretive Information

ARUP Ranges [1]

50 - 80 mg/dL

Other [2]

Infant, child    60-80 mg/dL

Adult               40-70 mg/dL

References

[1] ARUP Laboratory Test Directory; http://ltd.aruplab.com/Tests/Pub/0020515.

[2] Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 2012. 5th Ed. Burtis CA, Ashwood ER, Bruns DE, Eds. Saunders Elsevier, St. Louis, MO. ISBN: 0-7216-0189-8.

Dialysate

Clinical Indications

Peritoneal equilibration testing

Reference Interval and/or Interpretive Information

Glucose measurements in peritoneal dialysate are used as part of peritoneal equilibration testing (PET), which assists in the classification of peritoneal membrane function and in assessing inadequate dialysis. [1,2]

In such studies, dialysate glucose (at pre-defined times) is expressed as a ratio to the baseline dialysate concentration. [2]

See References for interpretive guidance.

References

[1] Henrich WL. 2009. Principles and practice of dialysis. 4th Ed. Lippincott Williams & Wilkins, Philadelphia, PA. ISBN:0781781639.

[2] Misra M, Khanna R. Peritoneal equilibration test. www.uptodate.com. [Accessed: 6/22/2015]

Pericardial

Clinical Indications

Supportive evidence for differentiation of exudates and transudates

Reference Interval and/or Interpretive Information

As supportive information for differentiating exudates from transudates, one study demonstrated that a pericardial fluid-to-serum glucose ratio of <1.0 had a sensitivity of 85%, although a specificity of only 12%. [1]

Pericardial fluid-to-serum glucose ratios were also low in culture-positive effusions. [1]

In a study of 30 patients undergoing elective open heart surgery (without evidence of pericardial disease), the “normal” pericardial fluid mean glucose concentration was 133 mg/dL (99% confidence interval, 106-159 mg/dL). [2]

This was also expressed as a “normal” mean fluid-to-serum glucose ratio of 1.0 (99% confidence interval, 0.8-1.2). [2]

References

[1] Meyers DG, Meyers RE, Prendergast TW. 1997. The usefulness of diagnostic tests on pericardial fluid. Chest. 111(5):1213-21. PMID: 9149572.

[2] Ben-Horin S, Shinfeld A, Kachel E, Chetrit A, Livneh A. 2005. The composition of normal pericardial fluid and its implications for diagnosing pericardial effusions. The American Journal of Medicine. 118:636-640. PMID: 15922695.

Peritoneal/Ascites

Clinical Indications

Evaluation of peritonitis and/or gut perforation

Reference Interval and/or Interpretive Information

Normal ascitic fluid glucose is similar to serum concentrations. [1]

Some reports have noted no statistical differences in glucose between sterile peritoneal fluid and ascitic fluid from spontaneous bacterial peritonitis. [2,3]

Specimens from patients with gut perforation (secondary bacterial peritonitis) did, however, have lower glucose concentrations. [2]

Other reports have noted decreased ascitic fluid-to-serum glucose ratios in spontaneous bacterial peritonitis. [4]

While ascites fluid glucose is generally considered as “unimportant” [2] and/or “not helpful” [5] in the work-up of peritoneal effusions, it is listed as an “optional” laboratory test (when there is suspicion of infection) in the American Association for the Study of Liver Disease practice guideline, Management of Adult Patients with Ascites Due to Cirrhosis (Update 2012). [6]

References

[1] Burgess LJ. 2004. Biochemical analysis of pleural, peritoneal, and pericardial effusions. Clin Chim Acta. 343:61-84. PMID: 15115678.

[2] Runyon BA, Hoefs JC. 1984. Ascitic fluid analysis in the differentiation of spontaneous bacterial peritonitis from gastrointestinal tract perforation into ascitic fluid. Hepatology. 4(3):447-450. PMID: 6724512.

[3] Runyon BA, Hoefs JC. 1985. Ascitic fluid chemical analysis before, during and after spontaneous bacterial peritonitis. Hepatology. 5(2):257-9. PMID: 3979958.

[4] Lee HH, Carlson RW, Bull DM. 1987. Early diagnosis of spontaneous bacterial peritonitis: values of ascitic fluid variables. Infection. 15(4):232-6. PMID: 3666966.

[5] Kjeldsberg CR, Straseski JA, Couturier MR, Cohen MB. Chapter 6: Peritoneal fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[6] Runyon BA. 2012. Practice Guideline. Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. American Association for the Study of Liver Diseases. http://www.aasld.org/sites/default/files/guideline_documents/adultascitesenhanced.pdf.

Pleural

Clinical Indications

Evaluation of pleural effusions

Reference Interval and/or Interpretive Information

Normal pleural fluid glucose is similar to serum concentrations. [1]

Pleural fluid transudates and most exudates usually have glucose concentrations of >60 mg/dL. [2]

Pleural fluid exudates with glucose concentrations <60 mg/dL have been associated with conditions such as parapneumonic effusion, tuberculosis, malignancy, empyema, and/or rheumatoid disease. [1,2,3,4]

References

[1] Hooper C, Lee YCG, Maskell N, on behalf of the BTS Pleural Guideline Group. 2010. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax. 65(Suppl 2):ii4-ii17. PMID: 20696692.

[2] Kjeldsberg CR, Grenache DG, Couturier MR, Cohen MB. Chapter 5: Pleural and pericardial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[3] Burgess LJ. 2004. Biochemical analysis of pleural, peritoneal, and pericardial effusions. Clin Chim Acta. 343:61-84. PMID: 15115678.

[4] Sahn SA. Getting the most from pleural fluid analysis. 2012. Respirology. 17: 270-277. PMID: 22059482.

Synovial

Clinical Indications

Evaluation of joint inflammation and/or septic arthritis

Reference Interval and/or Interpretive Information

Normal synovial fluid glucose concentrations are similar to corresponding serum (within ~10 mg/dL of a corresponding fasting serum concentration when the fluid was obtained at a 6-8 hr postprandial time point) [1], or approximately one half of corresponding non-fasting serum glucose. [2]

Low synovial fluid glucose has been associated with joint inflammation and/or septic arthritis. [1,2,3]

References

[1] Couturier MR, Straseski JA, Kjeldsberg CR. Chapter 7: Synovial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[2] Block DR, Franke DDH. Quick Guide to Body Fluid Testing. AACC Press (Washington, DC), 2015. ISBN 978-1-59425-180-1.

[3] Margaretten ME, Kohlwes J, Moore D, Bent S. 2007. Does this adult patient have septic arthritis? JAMA. 297(13):1478-1488. PMID: 17405973.

Lactate Dehydrogenase (LDH)

CSF

Clinical Indications

CSF evaluation (non-routine)

Reference Interval and/or Interpretive Information

Normal CSF LDH activities have been described as <40 U/L for adults and <70 U/L for neonates. [1]

They have also been described as about 10% of corresponding serum activity. [1]

Elevations of CSF LDH activity have been associated with a variety of neurologic disorders [1], but are generally not considered part of routine CSF testing.

References

[1] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[2] Jacobs DS, DeMott WR, Oxley DK. 2001. Jacob’s & DeMott Laboratory Test Handbook. 5th Ed. Lexi-Comp: Hudson, OH. ISBN: 1-930598-42-4.

Pericardial

Clinical Indications

Supportive evidence for differentiation of exudates and transudates

Reference Interval and/or Interpretive Information

LDH activity (>200 IU/L) and/or a fluid-to-serum LDH ratio of >0.6 is one component of Light’s criteria for differentiating exudates from transudates, and have been applied to pericardial fluids in one report. [1]

LDH activity and/or LDH fluid-to-serum ratio, however, have poor sensitivity for differentiating exudates from transudates on their own. [2]

In a study of 30 patients undergoing elective open heart surgery (without evidence of pericardial disease), the “normal” pericardial fluid mean LDH activity was 398 IU/L (99% confidence interval, 276-517 IU/L). [3]

This was also expressed as a “normal” mean fluid-to-serum LDH ratio of 2.4 (99% confidence interval, 1.3-3.5). [3]

References

[1] Burgess LJ, Reuter H, Taljaard JJF, Doubell AF. 2002. Role of biochemical tests in the diagnosis of large pericardial effusions. CHEST. 121(2):495-499. PMID: 11834663.

[2] Meyers DG, Meyers RE, Prendergast TW. 1997. The usefulness of diagnostic tests on pericardial fluid. Chest. 111(5):1213-21. PMID: 9149572.

[3] Ben-Horin S, Shinfeld A, Kachel E, Chetrit A, Livneh A. 2005. The composition of normal pericardial fluid and its implications for diagnosing pericardial effusions. The American Journal of Medicine. 118:636-640. PMID: 15922695.

Peritoneal/Ascites

Clinical Indications

Supportive evidence for differentiation of secondary from primary bacterial peritonitis

Reference Interval and/or Interpretive Information

Differentiation of secondary bacterial peritonitis (GI tract perforation) from spontaneous primary bacterial peritonitis is supported when two of the following three criteria are present: ascites fluid total protein >1g/dL, ascites fluid glucose <50 mg/dL, and ascites fluid LDH >225 IU/L (or greater than the serum upper reference limit). [1,2]

The American Association for the Study of Liver Disease practice guideline, Management of Adult Patients with Ascites Due to Cirrhosis (Update 2012) lists testing for ascitic fluid LDH as “optional (where there is suspicion of infection).” [3]

The serum-ascites albumin gradient demonstrates superior performance over either ascitic fluid LDH or ascites-to-serum LDH ratio for the differentiation of peritoneal transudates from exudates. [4,5,6]

References

[1] Runyon BA, Hoefs JC. 1984. Ascitic fluid analysis in the differentiation of spontaneous bacterial peritonitis from gastrointestinal tract perforation into ascitic fluid. Hepatology. 4(3):447-450. PMID: 6724512.

[2] Block DR, Franke DDH. Quick Guide to Body Fluid Testing. AACC Press (Washington, DC), 2015. ISBN 978-1-59425-180-1.

[3] Runyon BA. 2012. Practice Guideline. Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. American Association for the Study of Liver Diseases. http://www.aasld.org/sites/default/files/guideline_documents/adultascitesenhanced.pdf.

[4] Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG. 1992. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Int Med. 117(3):215-20. PMID: 1616215.

[5] Akriviadis EA, Kapnias D, Hadjigavriel M, Mitsiou A, Goulis J. 1996. Serum/ascites albumin gradient: its value as a rational approach to the differential diagnosis of ascites. Scand J Gastroenterol. 31(8):814-7. PMID: 8858753.

[6] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

Pleural

Clinical Indications

Supportive evidence for differentiation of exudates and transudates

Reference Interval and/or Interpretive Information

Light’s criteria can be used to identify most pleural exudative effusions if one or more of the following criteria are present: pleural fluid-to-serum protein ratio of >0.5, pleural fluid-to-serum LDH ratio of >0.6, or a pleural fluid LDH activity that is >2/3 the upper limit of a normal serum LDH activity. [1,2,3,4]

Heart failure associated misclassifications (by Light’s criteria) may be differentiated as trasudative effusions by subsequently evaluating a serum-to-pleural albumin gradient (>1.2 g/dL) and/or a serum-to-fluid protein gradient (>3.1 g/dL). [3,5]

References

[1] Light RW, MacGregor MI, Luchsinger PC, Ball WC. 1972. Pleural effusions: the diagnostic separation of transudates and exudates. Annals of Internal Medicine. 77:507-513. PMID: 4642731.

[2] Hooper C, Lee YCG, Maskell N, on behalf of the BTS Pleural Guideline Group. 2010. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax. 65(Suppl 2):ii4-ii17. PMID: 20696692.

[3] Porcel JM, Light RW. 2006. Diagnostic approach to pleural fluids in adults. American Family Physician. 73(7):1211-1220. PMID: 16623208.

[4] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[5] Porcel JM. 2013. Identifying transudates misclassified by Light’s criteria. Curr Opin Pulm Med. 19:362-367. PMID: 23508114.

Synovial

Clinical Indications

Synovial fluid evaluation

Reference Interval and/or Interpretive Information

Elevations in synovial fluid LDH activity (typically >250 U/L) have been associated with both noninfectious (inflammatory arthritis, crystal arthritis) and infectious (septic) arthritis. [1,2,3,4,5]

References

[1] Pejovic M, Stankovic A, Mitrovic DR. 1992. Lactate dehydrogenase activity and its isoenzymes in serum and synovial fluid of patients with rheumatoid arthritis and osteoarthritis. J Rheumatol. 19(4):529-533. PMID: 1593572.

[2] Margaretten ME, Kohlwes J, Moore D, Bent S. 2007. Does this adult patient have septic arthritis? JAMA. 297(13):1478-1488. PMID: 17405973.

[3] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[4] Couturier MR, Straseski JA, Kjeldsberg CR. Chapter 7: Synovial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[5] Shmerling RH, Delbanco TL, Tosteson ANA, Trentham DE. 1990. Synovial fluid tests: what should be ordered? JAMA. 264(8):1009-1014. PMID: 2198352.

Lipase

Biliary/Hepatic

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

May provide supportive evidence for pancreatic origin of fluid collection when considered along with a corresponding serum specimen.

References

None listed.

Drain

Clinical Indications

See Clinical Indications for individual source fluid types

Supportive evidence for pancreatic source of fluid accumulation

Reference Interval and/or Interpretive Information

Drain fluid lipase may provide supportive information as to pancreatic fluid source type if amylase levels are inconclusive, when considered along with a corresponding serum specimen.

Drain fluid amylase (as opposed to lipase) has been more extensively studied and included in recommendations for the evaluation of pancreatic fistula. [1]

In one retrospective study evaluating drain fluid after radical gastrectomy, fluid levels of both amylase and lipase were statistically higher in patients categorized as having complications associated with pancreatic leakage (versus those without complications). [2]

References

[1] Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, Sarr M, Taverso W, Buchler M, for the International Study Group on Pancreatic Fistula. 2005. Postoperative pancreatic fistula: An international study group (ISGPF) definition. Surgery. 138(1):8-13. PMID: 16003309.

[2] Seo KW, Yoon KY, Lee SH, Shin YM, Choi KH, Hwang HY. 2011. Amylase, lipase, and volume of drainage fluid in gastrectomy for the early detection of complications caused by pancreatic leakage. J Korean Surg Soc. 81:402-407. PMID: 2200041.

Pancreatic

Clinical Indications

Supportive evidence for pancreatic source of fluid accumulation

Reference Interval and/or Interpretive Information

Fluid lipase may provide supportive information as to pancreatic fluid source type if amylase levels are inconclusive, when considered along with a corresponding serum specimen.

Pancreatic fluid amylase (as opposed to lipase) has been more extensively studied for the differentiation of pancreatic cyst versus pseudocyst. [1]

Drain fluid amylase (as opposed to lipase) has been more extensively studied and included in recommendations for the evaluation of pancreatic fistula. [1]

References

[1] Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, Sarr M, Taverso W, Buchler M, for the International Study Group on Pancreatic Fistula. 2005. Postoperative pancreatic fistula: An international study group (ISGPF) definition. Surgery. 138(1):8-13. PMID: 16003309.

Pericardial

Clinical Indications

Supportive evidence for pancreatic source of fluid accumulation

Reference Interval and/or Interpretive Information

Limited published evidence.

May provide supportive evidence for pancreatic origin of fluid collection when considered along with a corresponding serum specimen.

Marked elevations of pericardial fluid lipase have been observed in a rare case of pancreatico-pericardial fistula.[1]

References

[1] Sommer CA, Wilcox CM. 2014. Pancreatico-pericardial fistula as a complication of chronic pancreatitis. F1000Res. 3:31. PMID: 24627800.

Peritoneal/Ascites

Clinical Indications

Evaluation of pancreatic ascites

Note that amylase has been more extensively studied and is therefore the preferred test

Reference Interval and/or Interpretive Information

Peritoneal fluid amylase (as opposed to lipase) has been more extensively studied and described in the evaluation of possible pancreatic ascites. [1]

There is insufficient evidence in the literature to support routine analysis of peritoneal fluid lipase activity.

May provide supportive evidence for pancreatic origin of fluid collections (if amylase levels are inconclusive), when considered along with a corresponding serum specimen.

References

[1] Kjeldsberg CR, Straseski JA, Couturier MR, Cohen MB. Chapter 6: Peritoneal fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

Pleural

Clinical Indications

Evaluation of suspected pancreatic-pleural fistula

Reference Interval and/or Interpretive Information

Pleural fluid amylase (as opposed to lipase) has been more extensively described, although it is usually not clinically indicated in routine pleural fluid analysis. [1,2]

Markedly elevated pleural fluid lipase (and amylase) have been observed with pancreatic-pleural fistula. [3]

References

[1] Branca P, Rodriguez RM, Rogers JT, Ayo DS, Moyers JP, Light RW. 2001. Routine measurement of pleural fluid amylase is not indicated. Arch Intern Med. 161(2):228-232. PMID: 11176736.

[2] Kjeldsberg CR, Grenache DG, Couturier MR, Cohen MB. Chapter 5: Pleural and pericardial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[3] Elkaoui H, Atoini F, Bouchentouf SM, El Omari F, Mahi M, Ait Ali A, Bounaim A, Sair K, Zentar A. 2012. Pancreatic-pleural fistula in chronic pancreatitis. Arab J Gastroenterol. 13(1):38-40. PMID: 22560825.

Synovial

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Lipase is not used in the routine analysis of synovial fluid.

There is limited published evidence regarding utility for measurement of synovial fluid lipase in cases of arthritis (with or without pancreatitis).

Elevations in synovial fluid lipase have been described in Pancreatitis-Panniculitis-Polyarthritis (PPP) syndrome, a rare disorder. [1,2]

References

[1] Loverdos I, Swan MC, Shekherdimian S, Al-Rasheed AA, Schneider R, Fish JS, Ngan BY, Adeli K, Lowe ME, Singh CP, Sevilla WMA, Langer JC, Gonska T. 2015. A case of pancreatitis, panniculitis and polyarthritis syndrome: elucidating the pathophysiologic mechanisms of a rare disorder. J Ped Surg Case Reports. 3:223-226.

[2] Lin CF, Chiu YM. 2011. Pancreatitis, panniculitis, and polyarthritis syndrome presenting with gouty arthritis: a case report. Journal of Medical Cases. 2(3):110-112.

Potassium (K⁺)

CSF

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Adults: 2.5-3.9 mmol/L [1,2; modified]

CSF potassium levels are often approximately 70% of corresponding serum potassium. [1]

References

[1] Tietz Clinical Guide to Laboratory Tests. 2006. 4th Ed. AHB Wu, Ed. Saunders Elsevier, St. Louis, MO. ISBN: 978-0-7216-7375-4.

[2] Wildemann B and Oschmann  P. 2010. Laboratory Diagnosis in Neurology. Thieme: New York, NY. ISBN: 3131495715.

Drain

Clinical Indications

See Clinical Indications for individual source fluid types

Reference Interval and/or Interpretive Information

Drain fluid potassium (K⁺) should be interpreted in the context of source and in correlation with serum results and/or other clinical evidence.

References

None listed.

Pancreatic

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Studies from healthy subjects undergoing endoscopic pancreatic function testing noted that the concentration of potassium (K⁺) in pancreatic fluid secretions is similar to concentrations observed in plasma. [1]

References

[1] Stevens T, Conwell DL, Zuccaro G, Van Lente F, Khandwala F, Purich E, Vargo JJ, Fein S, Dumot JA, Trolli R, O’Laughlin CO. 2004. Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects. Gastrointestinal Endoscopy. 60(3):351-355. PMID: 15332022.

Pericardial

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Pericardial fluid potassium (K⁺) levels are similar to those observed in blood. [1]

References

[1] Hutchin P, Nino HV, Suberman R. 1971. Electrolyte and acid-base composition of pericardial fluid in man. Arch Surg. 102:28-30. PMID: 5538765.

Peritoneal/Ascites

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

While limited published data is available on peritoneal electrolytes in healthy individuals, pericardial fluid potassium (K⁺) levels have been shown to correlate with venous plasma levels in one study of cirrhotic patients. [1]

Results should be interpreted with caution in specimens from patients undergoing peritoneal dialysis.

References

[1] Nguyen-Krac E, Thevenot T, Capron D, Dharancy S, Paupart T, Thabut D, Tiry C. 2008. Are ascitic electrolytes usable in cirrhotic patients?  Correlation of sodium, potassium, chloride, urea, and creatinine concentration in ascitic fluid and blood. Eur J Intern Med. PMID: 19046728.

Pleural

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Limited published data exists regarding normal pleural fluid electrolytes.

Pleural fluid potassium (K⁺) should be interpreted in correlation with serum results and/or other clinical evidence.

References

None listed.

Protein (Total)

CSF

Clinical Indications

Supportive information for the differentiation of bacterial, fungal, and viral CNS infection

Reference Interval and/or Interpretive Information

ARUP Ranges [1]

0 - 7 days: 40-120 mg/dL

8 days to 1 month: 20-40 mg/dL

1 month through adulthood: 14-45 mg/dL

References

[1] ARUP Lab Test Directory; http://ltd.aruplab.com/Tests/Pub/0020514.

Pericardial

Clinical Indications

Supportive evidence for differentiation of exudates and transudates

Reference Interval and/or Interpretive Information

Fluid-to-serum protein ratio of >0.5 is one component of Light’s criteria for differentiating exudates from transudates, and has been applied to pericardial fluids in one report. [1]

While the sensitivity in another study for detection of pericardial effusion was 97% (when using fluid total protein >3 g/dL) and 96% (when using fluid-to-serum protein ratio of >0.5), these tests have poor specificity (22% and 13%, respectively). [2]

In a study of 30 patients undergoing elective open heart surgery (without evidence of pericardial disease), the “normal” pericardial fluid total protein was 3.3 g/dL (99% confidence interval, 2.8-3.8 g/dL). [3]

This was also expressed as a “normal” mean fluid-to-serum protein ratio of 0.6 (99% confidence interval, 0.5-0.7). [3]

References

[1] Burgess LJ, Reuter H, Taljaard JJF, Doubell AF. 2002. Role of biochemical tests in the diagnosis of large pericardial effusions. CHEST. 121(2):495-499. PMID: 11834663.

[2] Meyers DG, Meyers RE, Prendergast TW. 1997. The usefulness of diagnostic tests on pericardial fluid. Chest. 111(5):1213-21. PMID: 9149572.

[3] Ben-Horin S, Shinfeld A, Kachel E, Chetrit A, Livneh A. 2005. The composition of normal pericardial fluid and its implications for diagnosing pericardial effusions. The American Journal of Medicine. 118:636-640. PMID: 15922695.

Peritoneal/Ascites

Clinical Indications

Supportive evidence for the evaluation of ascites

Supportive evidence for differentiation of secondary from primary bacterial peritonitis

Reference Interval and/or Interpretive Information

Serum ascites albumin gradient (SAAG) has been a more widely accepted method (versus traditional “exudate versus transudate” concepts using total protein) to differentiate ascites related to portal hypertension. [1,2]

The American Association for the Study of Liver Disease practice guideline, Management of Adult Patients with Ascites Due to Cirrhosis (Update 2012) includes the testing of ascitic fluid total protein as “routine”. [3]

Some sources have suggested that total protein measurement in peritoneal fluid is of “limited value”. [4,5]

Others have suggested that in patients with SAAG <1.1g/dL, ascites fluid total protein (using a 2.5 g/dL cutoff) is useful as a supplementary test in distinguishing several categories of potential causes for ascites. [6]

Differentiation of secondary bacterial peritonitis (GI tract perforation) from spontaneous primary bacterial peritonitis is supported when two of the following three criteria are present: ascites fluid total protein >1g/dL, ascites fluid glucose <50 mg/dL, and ascites fluid LDH >225 IU/L (or greater than the serum upper reference limit). [7,8]

References

[1] Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG. 1992. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Int Med. 117(3):215-20. PMID: 1616215.

[2] Burgess LJ. 2004. Biochemical analysis of pleural, peritoneal, and pericardial effusions. Clin Chim Acta. 343:61-84. PMID: 15115678.

[3] Runyon BA. 2012. Practice Guideline. Management of Adult Patients with Ascites Due to Cirrhosis: Update 2012. American Association for the Study of Liver Diseases. http://www.aasld.org/sites/default/files/guideline_documents/adultascitesenhanced.pdf.

[4] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[5] Kjeldsberg CR, Straseski JA, Couturier MR, Cohen MB. Chapter 6: Peritoneal fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[6] McGibbon A, Chen GI, Peltekian KM, van Zanten SV. 2007. An evidence-based manual for abdominal paracentesis. Dig Dis Sci. 52(12):3307-15. PMID: 17393312.

[7] Runyon BA, Hoefs JC. 1984. Ascitic fluid analysis in the differentiation of spontaneous bacterial peritonitis from gastrointestinal tract perforation into ascitic fluid. Hepatology. 4(3):447-450. PMID: 6724512.

[8] Block DR, Franke DDH. Quick Guide to Body Fluid Testing. AACC Press (Washington, DC), 2015. ISBN 978-1-59425-180-1.

Pleural

Clinical Indications

Differentiation of exudates and transudates

Reference Interval and/or Interpretive Information

Light’s criteria can be used to identify most pleural exudative effusions if one or more of the following criteria are present: pleural fluid-to-serum protein ratio of >0.5, pleural fluid-to-serum LDH ratio of >0.6, or a pleural fluid LDH activity that is >2/3 the upper limit of a normal serum LDH activity. [1,2,3,4]

Heart failure associated misclassifications (by Light’s criteria) may be differentiated as transudative effusions by subsequently evaluating a serum-to-pleural albumin gradient (>1.2 g/dL) and/or a serum-to-fluid protein gradient (>3.1 g/dL). [3,5]

References

[1] Light RW, MacGregor MI, Luchsinger PC, Ball WC. 1972. Pleural effusions: the diagnostic separation of transudates and exudates. Annals of Internal Medicine. 77:507-513. PMID: 4642731.

[2] Hooper C, Lee YCG, Maskell N, on behalf of the BTS Pleural Guideline Group. 2010. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax. 65(Suppl 2):ii4-ii17. PMID: 20696692.

[3] Porcel JM, Light RW. 2006. Diagnostic approach to pleural fluids in adults. American Family Physician. 73(7):1211-1220. PMID: 16623208.

[4] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[5] Porcel JM. 2013. Identifying transudates misclassified by Light’s criteria. Curr Opin Pulm Med. 19:362-367. PMID: 23508114.

Synovial

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

The reference range for total protein in synovial fluid has been described as 1.0-3.0 g/dL. [1]

Synovial fluid total protein (typically >3.0 g/dL) may be found in a variety of inflammatory, infectious, or hemorrhagic conditions. [2]

Routine testing is generally not recommended as results are often “not informative.” [3,4]

References

[1] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[2] Couturier MR, Straseski JA, Kjeldsberg CR. Chapter 7: Synovial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[3] Shmerling RH, Delbanco TL, Tosteson ANA, Trentham DE. 1990. Synovial fluid tests: what should be ordered? JAMA. 264(8):1009-1014. PMID: 2198352.

[4] Margaretten ME, Kohlwes J, Moore D, Bent S. 2007. Does this adult patient have septic arthritis? JAMA. 297(13):1478-1488. PMID: 17405973.

Rheumatoid Factor (RF)

CSF

Clinical Indications

Not well-defined (non-routine)

Reference Interval and/or Interpretive Information

Elevations in CSF rheumatoid factor (RF) have been observed in some cases of central nervous system rheumatoid meningitis. [1,2.3]

References

[1] Markenson JA, McDougal JS, Tsairis P, Lockshin MD, Christian CL. 1979. Rheumatoid meningitis: a localized immune process. Annals of Internal Medicine. 90:786-789. PMID: 312046.

[2] Ii Y, Kuzuhara S. 2009. Rheumatoid cranial pachymeningitis successfully treated with long-term corticosteroid. Rheumatol Int. 29(5):583-5. PMID: 18807253.

[3] Inan AS, Masatlioglu S, Ozyurek SC, Engin D, Erdem I. 2011. Unusual central nervous system involvement of rheumatoid arthritis: successful treatment with steroid and azathioprine. Rheumatol Int. 31(10):1383-5. PMID: 20012963.

Pericardial

Clinical Indications

Not well-defined (non-routine)

Reference Interval and/or Interpretive Information

There is limited published evidence regarding testing of rheumatoid factor (RF) in pericardial fluid. [1]

References

[1] Ball GV, Schrohenloher R, Hester R. 1975. Gamma complexes in rheumatoid pericardial fluid. Am J Med. 58(1):123-8. PMID: 46702.

Pleural

Clinical Indications

Not well-defined (non-routine)

Reference Interval and/or Interpretive Information

While pleural fluid rheumatoid factor (RF) may be detected in patients with rheumatoid pleural effusions and rheumatoid pleuritis, it is not specific for these conditions and/or may simply reflect serum concentrations. [1,2,3,4,5,6]

References

[1] Levine H, Szanto M, Grieble HG, Back G, Anderson TO. 1968. Rheumatoid factor in nonrheumatoid pleural effusions. Ann Intern Med. 69(3):487-492. PMID: 5673168.

[2] Allan JS, Donahue DM, Garrity JM. 2005. Rheumatoid pleural effusion in the absence of arthritic disease. Ann Thorac Surg. 80(4):1519-21. PMID: 16181910.

[3] Balbir-Gurman A, Yigla M, Nahir AM, Braun-Moscovici Y. 2006. Rheumatoid pleural effusion. Semin Arthritis Rheum. 35(6):368-78. PMID: 16765714.

[4] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[5] Hassan T, Al-Alawi M, Chotirmall SH, McElvaney NG. 2012. Pleural fluid analysis: standstill or a work in progress. Pulm Med. 2012:716235. PMID: 22448326.

[6] Kjeldsberg CR, Grenache DG, Couturier MR, Cohen MB. Chapter 5: Pleural and pericardial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

Synovial

Clinical Indications

Not well defined (non-routine)

Reference Interval and/or Interpretive Information

Synovial fluid rheumatoid factor (RF) measurements are generally not considered to be diagnostically helpful. [1,2]

RF has been detected in synovial fluid in only ~60% of patients with rheumatoid arthritis, and typically in titers slightly lower than those observed in serum. [2,3]

References

[1] Koopman WJ, Moreland LW. 2005. Arthritis and allied conditions: a textbook of rheumatology. Lippincott Williams & Wilkins: Philadelphia, PA. ISBN: 0-7817-4671-X.

[2] Couturier MR, Straseski JA, Kjeldsberg CR. Chapter 7: Synovial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.

[3] Cracchiolo A, Barnett EV. 1972. The role of immunological tests in routine synovial fluid analysis. J Bone Joint Surg Am. 54(4):828-40. PMID: 4341270.

Sodium (Na⁺)

CSF

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

136-150 mmol/L [1]

References

[1] Tietz Clinical Guide to Laboratory Tests. 2006. 4th Ed. AHB Wu, Ed. Saunders Elsevier, St. Louis, MO. ISBN: 978-0-7216-7375-4.

Drain

Clinical Indications

See Clinical Indications for individual source fluid types

Reference Interval and/or Interpretive Information

Drain fluid sodium (Na⁺) should be interpreted in the context of source and in correlation with serum results and/or other clinical evidence.

References

None listed.

Pancreatic

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Studies from healthy subjects undergoing endoscopic pancreatic function testing noted that the concentration of sodium (Na⁺) in pancreatic fluid secretions is similar to the concentrations observed in plasma. [1]

References

[1] Stevens T, Conwell DL, Zuccaro G, Van Lente F, Khandwala F, Purich E, Vargo JJ, Fein S, Dumot JA, Trolli R, O’Laughlin CO. 2004. Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects. Gastrointestinal Endoscopy. 60(3):351-355. PMID: 15332022.

Pericardial

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Pericardial fluid sodium (Na⁺) levels are similar to those observed in blood. [1]

References

[1] Hutchin P, Nino HV, Suberman R. 1971. Electrolyte and acid-base composition of pericardial fluid in man. Arch Surg. 102:28-30. PMID: 5538765.

Peritoneal/Ascites

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

While limited published data is available on peritoneal electrolytes in healthy individuals, pericardial fluid sodium (Na⁺) levels have been shown to correlate with venous plasma levels in one study of cirrhotic patients. [1]

Results should be interpreted with caution in specimens from patients undergoing peritoneal dialysis.

References

[1] Nguyen-Krac E, Thevenot T, Capron D, Dharancy S, Paupart T, Thabut D, Tiry C. 2008. Are ascitic electrolytes usable in cirrhotic patients?  Correlation of sodium, potassium, chloride, urea, and creatinine concentration in ascitic fluid and blood. Eur J Intern Med. PMID: 19046728.

Pleural

Clinical Indications

Not well-defined

Reference Interval and/or Interpretive Information

Limited published data exists regarding “normal” pleural fluid electrolytes.

References

None listed.

Triglycerides

Drain

Clinical Indications

See Clinical Indications for individual source fluid types

Detection of chyle leakage

Reference Interval and/or Interpretive Information

Drain fluid triglycerides should be interpreted in the context of source (e.g., pleural, peritoneal, etc.) and in correlation with serum results and/or other clinical evidence.

Frequently used in the detection of chyle leakage. [1,2,3,4,5]

See comments under each fluid type, as applicable

References

[1] Roh JL, Kim DH, Park CI. 2008. Prospective identification of chyle leakage in patients undergoing lateral neck dissection for metastatic thyroid cancer. Ann Surg Oncol. 15(2):424-9. PMID: 17999116.

[2] Roh JL, Yoon YH, Park CI. 2008. Chyle leakage in patients undergoing thyroidectomy plus central neck dissection for differentiated papillary thyroid carcinoma. Ann Surg Oncol. 15(9):2576-80. PMID: 18592317.

[3] Taylor J, Jayasinghe S, Barthelmes L, Chare M. 2011. Chyle leak following axillary lymph node clearance – a benign complication: review of the literature. Breast Care. 6:130-132. PMID: 21673824.

[4] Wilkinson J, Pennefather SH, McCahon RA. 2011. Thoracic Anesthesia. Oxford University Press: New York, NY. ISBN: 978-0-19-956309-8.

[5] Leaper D, Whitaker I. 2010. Post-operative complications. 2nd Ed. Oxford University Press: New York, NY. ISBN: 978-0-19-954626-8.

Pericardial

Clinical Indications

Supportive information in the diagnosis of chylopericardium [1]

Reference Interval and/or Interpretive Information

Pericardial fluid triglycerides >500 mg/dL and a pericardial fluid cholesterol-to-triglyceride ratio of <1 are two factors which support a diagnosis of chylopericardium. [2,3]

References

[1] Burgess LJ. 2004. Biochemical analysis of pleural, peritoneal, and pericardial effusions. Clin Chim Acta. 343:61-84. PMID: 15115678.

[2] Hoit BD. Chylopericardium and cholesterol pericarditis. www.uptodate.com. [Accessed: 6/22/2015].

[3] Dib C, Tajik AJ, Park S, Kheir ME, Khandieria B, Mookadam F. 2008. Chylopericardium in adults: a literature review over the past decade (1996-2006). J Thorac Cardiovasc Surg. 136:650-656. PMID: 18805268.

Peritoneal/Ascites

Clinical Indications

Supportive information in the diagnosis of chylous ascites

Reference Interval and/or Interpretive Information

A peritoneal fluid triglyceride concentration that is greater (usually 2X to 8X higher) than a corresponding serum specimen supports a diagnosis of chylous ascites. [1]

Others have suggested absolute triglyceride cutoffs (such as >200 mg/dL or >110 mg/dL) to support the diagnosis of chylous ascites. [2,3]

Correlation with a corresponding serum specimen (even when using absolute cutoffs) may provide useful information as triglycerides in serum and chyle may change based on nutritional status.

References

[1] Aalami OO, Allen DB, Organ CH. 2000. Chylous ascites: a collective review. Surgery. 128(5):761-778. PMID: 11056439.

[2] Cárdenas A, Gelrud A, Chopra S. Chylous, bloody, and pancreatic ascites. www.uptodate.com. [Accessed: 6/22/2015].

[3] Kopcinovic LM, Culej J. 2014. Pleural, peritoneal, and pericardial effusions – a biochemical approach. Biochemia Medica. 24(1):123-37. PMID: 24627721.

Pleural

Clinical Indications

Differentiation of chylothorax from pseudochylothorax

Reference Interval and/or Interpretive Information

Pleural fluid triglycides can be used along with cholesterol to help distinguish chylothorax (triglycerides >110 mg/dL, cholesterol <200 mg/dL) from pseudochylothorax (triglycerides <50 mg/dL, cholesterol >200 mg/dL). [1,2,3,4]

References

[1] Hillerdal G. 1997. Chylothroax and pseudochylothroax. Eur Respir J. 10(5):1157-62. PMID: 9163662.

[2] McGrath EE, Blades Z, Anderson PB. 2009. A systematic approach to the investigation and diagnosis of a unilateral pleural effusion. Int J Clin Pract. 63(11):1653-9. PMID: 19765100.

[3] McGrath EE, Blades Z, Anderson PB. 2010. Chylothorax: aetiology, diagnosis, and therapeutic options. Respiratory Medicine. 104:1-8. PMID: 19766473.

[4] Staats BA, Ellefson RD, Budahn LL, Dines DE, Prakash UB, Offord K. 1980. The lipoprotein profile of chylous and nonchylous pleural effusions. Mayo Clin Proc. 55(11):700-704. PMID: 7442324.

Uric Acid

Drain

Clinical Indications

Not well defined (non-routine)

Reference Interval and/or Interpretive Information

Drain fluid uric acid (urate) should be interpreted in the context of source and in correlation with serum results and/or other clinical evidence.

References

None listed.

Peritoneal/Ascites

Clinical Indications

Not well defined (non-routine)

Reference Interval and/or Interpretive Information

Limited published data exists regarding peritoneal fluid uric acid.

Peritoneal fluid uric acid (urate) should be interpreted in correlation with serum results and/or other clinical evidence.

References

None listed.

Pleural

Clinical Indications

Not well defined (non-routine)

Reference Interval and/or Interpretive Information

Limited published data exists regarding pleural fluid uric acid. [1]

Pleural fluid uric acid (urate) should be interpreted in correlation with serum results and/or other clinical evidence.

References

[1] Uzun K, Vural H, Ozer F, Imecik O. 2000. Diagnostic value of uric acid to differentiate transudates from exudates. Clin Chem Lab Med. 38(7):661-665. PMID: 11028772.

Synovial

Clinical Indications

Supportive evidence for the diagnosis of gout (non-routine)

Reference Interval and/or Interpretive Information

Diagnosis of gout is based on monosodium urate crystal identification in synovial fluid by polarized microscopy.

In cases where microscopy is not available (or when crystals are not observed), measurement of synovial fluid uric acid (urate) may provide additional supportive information for the diagnosis of gout. [1,2]

Synovial fluid uric acid concentrations significantly greater than the upper reference limit for serum uric acid may support such a diagnosis. [2]

References

[1] Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

[2] Couturier MR, Straseski JA, Kjeldsberg CR. Chapter 7: Synovial fluid. In Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds. ASCP Press: Chicago, IL, 2015. ISBN: 978-089189-5824.


Suggested References

Additional Resources and Clinical Information

Kjeldsberg’s Body Fluid Analysis. Hussong JW and Kjeldsberg CR, Eds.  ASCP Press: Chicago, IL, 2015. ISBN 978-089189-5824.

Karcher DS, McPherson RA. Chapter 29: Cerebrospinal, synovial, serous body fluids, and alternative specimens. In Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd Ed. McPherson RA, Pincus MR. Eds. Elsevier Saunders: Philadelphia, PA, 2011. ISBN: 1437709745.

Burgess LJ. 2004. Biochemical analysis of pleural, peritoneal, and pericardial effusions. Clin Chim Acta. 343:61-84. PMID: 15115678.

Guidance on Body Fluid Validations

Block DR, Franke DDH. Quick Guide to Body Fluid Testing. AACC Press (Washington, DC), 2015. ISBN 978-1-59425-180-1.

CLSI. Analysis of Body Fluids in Clinical Chemistry; Approved Guideline. CLSI document C49-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2007.


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