Pericardial fluid examination

Laboratory diagnosis of Pericardial fluid examination

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.

7. 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

8. 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

9. 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

10. 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

11. 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.

12. 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.

13. 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

14. 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

15. 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)

16. 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)

17. 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)

18. 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.

19. 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.

20. 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.

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

22. 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.

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

24. 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.

25. 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.