This document discusses the analysis of pericardial fluid. It begins by describing the normal composition and amount of pericardial fluid. It then discusses the causes of pericardial effusions, including infections, cancers, autoimmune diseases, and others. The document outlines the indications for pericardial fluid analysis and describes the reference values and characteristics of transudative versus exudative fluid. It concludes by discussing specific tests that can be done on pericardial fluid and their clinical significance, including ADA, tumor markers, cytology, and molecular tests.

1. PERICARDIAL FLUID EXAMINATION
Dr Abdul Hafeez Kandhro
Senior Lecturer
B.Sc, M.Sc; Medical Technology,
M.Phil Biochemistry
Ph.D. Medical Technology
(Mahidol University, Bangkok , Thailand)

2. Pericardial fluid analysis
• Pericardial fluid is an ultrafiltrate of plasma that
lies within the pericardial sac, acting as a lubricant
between the visceral and parietal layer of the
pericardium.
• The space normally contains 15-50 mL of thin,
clear, straw-colored fluid that is enriched in
molecules from the myocardial interstitial fluid
and lymphatic drainage.
• Molecules up to 40 kDA are commonly diffused
through the ventricular myocytes.

3. Pericardial fluid analysis
• Pericardium isolates the heart from the adjacent tissues,
allowing it's free movement within the boundaries of the
pericardial cavity and is filled with a small amount of fluid
which is called pericardial fluid.
• The development of a pericardial effusion may have
important implications for prognosis (as in patients with
intrathoracic neoplasm), While in diagnosis (as in
myopericarditis or acute pericarditis), or both (as in
dissection of the ascending aorta).

4. Pericardial fluid analysis
• The composition of the fluid is believed to be a result of
Starlings forces and the gradients between hydrostatic
and osmotic pressure of the pericardial fluid and plasma.
• The fluid may subsequently reflect any circumstances
imposed onto the heart, ranging from trauma and
infections to metabolic derangements.

5. Pericardial fluid analysis
• When larger amounts of fluid accumulate (pericardial
effusion) or when the pericardium becomes scarred and
inelastic, one of three pericardial compressive syndromes
may occur:
• Cardiac tamponade
• Constrictive pericarditis
• Effusive-constrictive pericarditis
• Cardiac tamponade – Cardiac tamponade, which may be
acute or subacute, is characterized by the accumulation
of pericardial fluid under pressure. Variants include low
pressure (occult) and regional cardiac tamponade.

6. Pericardial fluid analysis
• Constrictive pericarditis – Constrictive pericarditis is the
result of scarring and consequent loss of elasticity of the
pericardial sac. Pericardial constriction is typically
chronic, but variants include subacute, transient, and
occult constriction.
• Effusive-constrictive pericarditis – Effusive-constrictive
pericarditis is characterized by underlying constrictive
physiology with a coexisting pericardial effusion, usually
with cardiac tamponade.
• Such patients may be mistakenly thought to have only
cardiac tamponade; however, elevation of the right atrial
and pulmonary wedge pressures after drainage of the
pericardial fluid points to the underlying constrictive
process.

8. The etiology of pericardial effusion
• The etiology of pericardial effusion includes the
following:
• Idiopathic pericarditis
• Infections
• Bacteria [Staphylococcus, Streptococcus, Haemophilus,
Neisseria, Chlamydia]
• Mycobacterium tuberculosis
• Viral (coxsackievirus A and B, Echovirus, Adenovirus, HIV)
• Fungal – Aspergillus, Candida, Histoplasma,
Blastomycosis, Coccidioidomycosis
• Protozoan – Echinococcus, Amebiasis, Toxoplasmosis

9. The etiology of pericardial effusion
• Neoplasms
• Metastatic/paraneoplastic (breast, lung, leukemia,
lymphoma)
• Primary – Teratoma, lipoma, angioma,
rhabdomyosarcoma
• Autoimmune connective tissue disease
• Rheumatic diseases – Systemic lupus erythematosus,
Rheumatoid arthritis, Ankylosing spondylitis,
Scleroderma, Wegener granulomatosis
• Non-Rheumatic diseases -Inflammatory bowel disease
(Ulcerative colitis, Crohn disease), Giant cell arteritis,
Polyarteritis nodosa, Sarcoidosis, Rheumatic fever

10. The etiology of pericardial effusion
• Trauma (eg, blunt and penetrating trauma, radiofrequency catheter
ablation of atrial fibrillation)
• Metabolic causes
• Hypothyroidism
• Anorexia nervosa
• Uremia
• Chylopericardium
• Drugs (hydralazine, isoniazid, procainamide, phenytoin,
anticoagulants)
• Pericardial injury syndrome (postmyocardial infarction effusion,
posttraumatic effusion, postcardiotomy)
• Radiation Hyperlipidemia
• Severe pulmonary hypertension
• Thoracic aortic disease – Leakage or rupture

11. Indications/Applications
• Invasive pericardial drainage procedure (ie,
pericardiocentesis or open surgical drainage) and the
diagnostic analysis of pericardial fluid is warranted in the
following cases:
• Patients with a strong suspicion of purulent or TB
pericarditis
• To determine if the pericardial effusion is secondary to
neoplastic pericardial involvement

12. Indications/Applications
• Pericardial effusion of unknown origin
• Patients with massive idiopathic chronic pericardial
effusion
• Pericardial tamponade caused by uncontrolled pericardial
effusion with hemodynamic instability
• Considerations must be taken with coagulopathic
patients with increased risk of bleeding. For diagnostic or
nonemergent pericardiocentesis, imaging is imperative.

13. Interfering Factors
• Factors that may alter the results of the study
Bloody fluid may be the result of a traumatic tap.
• Other Considerations:
• Unknown hyperglycemia or hypoglycemia may be
misleading in the comparison of fluid and serum glucose
levels.
• Therefore, it is advisable to collect comparative serum
samples a few hours before performing
pericardiocentesis.

14. Pericardial Fluid Reference Value
Appearance Clear
Color Pale yellow
Glucose Parallels serum values
Red blood cell (RBC) count None seen
White blood cell (WBC) count Less than 300 cells/uL
Culture No growth
Gram stain No organisms seen
Cytology No abnormal cells seen
Lab Diagnosis
Normal Pericardial fluid

15. Lab Diagnosis
Characteristic Transudate Exudate
Appearance Clear to pale yellow Cloudy, bloody, or turbid
Specific gravity Less than 1.015 Greater than 1.015
Total protein Less than 2.5 g/dl Greater than 3 g/dl
Fluid protein–to–serum
protein ratio
Less than 0.5 Greater than 0.5
Lactate dehydrogenase
(LDH)
Less than 2/3 the upper
limit of normal serum
LDH
Greater than 2/3 the
upper limit of normal
serum LDH
Fluid LDH–to–serum LDH
ratio
Less than 0.6 Greater than 0.6
Fluid cholesterol Less than 55 mg/dL Greater than 55 mg/dl
WBC count Less than 100 cells/uL
Greater than 1,000
cells/uL

16. Potential Medical Diagnosis: Clinical Significance of Results
• Condition/Test Showing Increased Result
• Bacterial pericarditis (RBC count, WBC count with a
predominance of neutrophils)
• Hemorrhagic pericarditis (RBC count, WBC count)
• Malignancy (RBC count, abnormal cytology)
• Post–myocardial infarction syndrome, also called Dressler
syndrome (RBC count, WBC count with a predominance
of neutrophils)
• Rheumatoid disease or systemic lupus erythematosus
(SLE) (RBC count, WBC count)

17. Potential Medical Diagnosis: Clinical Significance of Results
• Condition/Test Showing Increased Result
• Tuberculous or fungal pericarditis (RBC count, WBC count
with a predominance of lymphocytes)
• Viral pericarditis (RBC count, WBC count with a
predominance of neutrophils)
• Condition/Test Showing Decreased Result
• Bacterial pericarditis (glucose)
• Malignancy (glucose)
• Rheumatoid disease or SLE (glucose)

18. Potential Medical Diagnosis: Clinical Significance of Results
• Bloody pericardial effusion
• Iatrogenic: The most common cause in developed
countries. This includes the effect of anticoagulant
therapy, trauma, post invasive cardiac procedures (ie,
postpericardiotomy syndrome, transcatheter
interventions).
• Malignancy
• Atherosclerotic heart disease (mainly complications of
acute myocardial infarction)

19. Potential Medical Diagnosis: Clinical Significance of Results
• Bloody pericardial effusion
• Tuberculosis: This condition remains to be one of the
most common causes of pericarditis/pericardial effusion
in Africa and TB-dominant developing countries.
Approximately 80% of cases of tuberculous pericarditis
are bloodstained effusions.
• Idiopathic
• If the fluid is milky, consider the involvement of the
lymphatic system (ie, chylopericardium). If the fluid is
cloudy and turbulent, it is suggestive of signs of increased
capillary leakage and leukocytosis and is concerning for
infectious effusion.

20. Potential Medical Diagnosis: Clinical Significance of Results
• Myxedema (severely advanced hypothyroidism) is
associated with low WBC count.
• A low ratio of pericardial effusion (PE) and serum glucose
suggests infection. This low ratio, along with an elevated
neutrophil count in pericardial fluid, is suggestive for
bacterial pericardial effusion.

21. Adenosine Deaminase & B-type natriuretic peptide
• Elevated pericardial ADA activity is suggestive of TB
pericarditis. The test is a valid diagnostic tool applicable
regardless of HIV status.
• A lower ADA level may be observed in patients with HIV
who have a low CD4 count. ADA levels of more than 40
U/L are diagnostic for TB pericarditis.
• Elevation of B-type natriuretic peptide (BNP) levels in
pericardial fluid is noted in patients with postmyocardial
infarction, reflecting the stretching of ventricular
cardiomyocytes after an injury to the myocardium.

22. Culture
• If bacterial infection is suspected, at least 3 cultures of
pericardial fluid for aerobes and anaerobes as well as
blood cultures are required.

23. Immunological tests
• Complement levels, ANA and anti-dsDNA can be
measured in the setting of pericardial effusion and
systemic lupus erythematous to help identify pericardial
membrane involvement.

24. Tumor Markers for Malignancy
• Different types of cancer can have different tumor
markers. Various tumor markers have been tested, such
as:
a) Carcinoembryonic antigen (CEA)
b) Carbohydrate antigen (CA) 19-9
c) Carbohydrate antigen (CA) 72-4
d) Squamous cell carcinoma (SCC) antigen
e) Neuron-specific enolase (NSE)
f) Serum cytokeratin 19 fragments (CYFRA 21-1)
g) BerEp4
h) Hyaluronan

25. Cytology
• Cytologic study of pericardial fluid helps identify
malignancy as the cause of pericardial effusion by
detecting neoplastic cells within the fluid. However, it is
not always straightforward.
• Nonmalignant cells can be morphologically
indistinguishable from malignant cells. For example,
mesothelial cell’s morphology can be benign,
hyperplastic, reactive, or malignant.

26. Molecular Tests
• Polymerase chain reaction (PCR) has been used to detect
M tuberculosis using nucleic acid amplification.
• Molecular procedures involving direct amplification from
sterile sites is an alternative approach in identification of
pathogens associated with pericardial effusion.
• Etiological diagnosis have been shown to be significantly
higher with use of PCR-based diagnosis than use of
culture only.