Pericardial Fluid Analysis: Reference Range, Interpretation, Background (2022)

Bloody pericardial effusion [2]

  • Iatrogenic: The most common cause in developed countries. This includes the effect of anticoagulant therapy, trauma, postinvasive cardiac procedures (ie, postpericardiotomy syndrome, transcatheter interventions).

  • Malignancy

  • Atherosclerotic heart disease (mainly complications of acute myocardial infarction)

  • 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

    (Video) Pericardial Fluid Analysis

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.

Routine tests

The following conditions are associated with elevated WBC counts:

  • Elevated levels of leukocytes (>10,000/mcl) with neutrophil predominance suggests a bacterial or rheumatic cause.

  • The monocyte count is noted to be highest in malignant effusions.

Myxedema is associated with low WBC count.

At this time, no standardized biochemical or cell count criteria meets a statistical relationship between specific causes of effusion. However, an elevated WBC level is suggestive of an inflammation within the pericardium.

(Video) Echocardiography assessment of Pericardial Effusion 1

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. [3]

According Light et al’s criteria for pleural fluid, an exudate is considered if one of the following parameters are met: the total protein fluid-to-serum ratio is higher than 0.5, the LDH fluid-to-serum ratio is more than 0.6, or the LDH fluid level exceeds two thirds of upper limit of normal serum level. [4] According to Burgess et al, Light et al’s criteria was applied to pericardial effusion and sensitivity and specificity were reported to be 98% and 72%, respectively. [5]

However, debate still surrounds the inconsistent data regarding the adaptation of Light et al’s criteria of pleural effusion to pericardial effusion. [6, 3] Dissimilar to pleural fluid, the establishment of exudative versus transudative effusion cannot be implied with the use of this criteria. A study by Ben-Horin et al noted that 118 of 120 patients with pericardial fluid fit the category for exudative under Light et al’s criteria. [3] Spodick also demonstrates that patients with improving congestive heart failure present with pseudoexduative effusion, likely secondary to rapid reabsorption of water compared with proteins and LDH in uncomplicated heart failure. [7]

In conclusion, analyses of pericardial fluid protein level (>0.5) and LDH (>0.6) can suggest between exudates from transudates pericardial fluid, [8] but should not be used as a sole diagnostic framework. Interpretation of the results should be applied with patient’s clinical presentation and other relevant laboratory results.

Complement levels, ANA and anti-ds DNA can be measured in the setting of pericardial effusion and systemic lupus erythematous to help identify pericardial membrane involvement.

If bacterial infection is suspected, at least 3 cultures of pericardial fluid for aerobes and anaerobes as well as blood cultures are required. [8] Gram stains in bacterial infection pericardial fluid have a specificity of 99% but a sensitivity of only 38% compared with bacterial cultures. [9] The use of Gram stain and culture is generally limited in mycobacterial, viral, and fungal infection.

(Video) Pericarditis and pericardial effusions - causes, symptoms, diagnosis, treatment, pathology

Special tests

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. Data on pericardial fluid analysis are limited; however, a study by Rakha et al found the overall sensitivity of cytology evaluation of pleural fluid in the diagnosis of malignant mesothelioma was 53%. It appears to be useful in patients with epithelioid and biphasic pleural malignant mesothelioma; however, the sensitivity could be as low as 20% in sarcomatoid malignancy mesothelioma cases. [10]

A similar issue was described in cases of lymphoma. Ancillary studies, including immunocytochemistry, morphometry, flow cytometry, and cytogenetics/molecular genetics on effusion specimens may be helpful in differentiating lymphoma from reactive lymphocytoses with higher sensitivity. [11]

Cytologically negative effusion does not exclude malignancy as the cause. In a retrospective study of 82 patients with nonsmall cell lung cancer (NSCLC) and cardiac tamponade, no survival difference was noted between patients with positive pericardial fluid cytology findings for cancer (60 patients) compared with those with negative cytology findings (22 patients). Significant survival difference was reported after systemic chemotherapy was initiated. The authors concluded that in patients with advanced NSCLC and cardiac tamponade, the most likely cause of the pericardial effusion is the cancer itself, regardless of the cytology results. [12, 13]

The use of tumor marker measurement in pericardial fluid may be helpful in cytologically negative pericardial fluid. The interpretation of these tumor marker levels is similar to that in serum. Malignant pericardial effusion is associated with high levels of tumor markers. However, low levels of these markers do not exclude neoplastic involvement of the pericardial membrane. The cut-off of these markers in pericardial fluid is not yet clear at this point. Moreover, 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, and hyaluronan.

Szturmowicz reported considerably higher median CEA and CYFRA 21-1 concentrations in malignant pericardial effusion compared with nonmalignant pericardial effusion (80 ng/mL [0-317] vs. 0.5 ng/mL [0-18.4], and 260 ng/mL [5.3-10080] vs 22.4 ng/mL, respectively). In this study, the optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL, and CEA 5 ng/mL. CYFRA 21-1 of more than 100 ng/mL or CEA of more than 5 ng/mL were found in 14 of 15 patients with malignant pericardial effusion and negative pericardial fluid cytology findings. [14]

Similar results were found in a study by Karatolios et al that included 29 patients with proven malignant pericardial effusion and 25 patients with nonmalignant causes. The mean concentrations of the CEA, CA 72-4, and CA 19-9 were significantly higher in malignant pericardial effusions than in nonmalignant effusions. Pericardial fluid CA 72-4 levels >1 kU/L had 72% sensitivity and 96% specificity in differentiating malignant pericardial effusions from effusions due to benign conditions. [15]

(Video) Pleural Fluid Analysis

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 (sensitivity 88%, specificity 83%). [16] Elevated levels of more than 200 pg/L are suggestive of tuberculous pericarditis. (sensitivity 92%, specificity 100%). [17] A definite diagnosis of TB pericarditis is the presence of tubercle bacilli in pericardial fluid or on histological section of a pericardium. However, conventional culture for TB has a lower sensitivity, and inoculation of fluid into double-strength liquid Kirchner culture medium is recommended because this may increase the yield from 53% to 75%. [16, 17]

Polymerase chain reaction (PCR) has been used to detect M tuberculosis using nucleic acid amplification. An advantage of the test is its ability to rapidly identify M tuberculosis with as small as 1 mcL of pericardial fluid. The technique, however, is less sensitive than established methods and is prone to contamination and false-positive results. At this time, PCR is not an ideal diagnostic tool to detect tuberculous pericarditis. Other methods as suggested above should be considered beforehand.

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, increasing the number of cases from 13.9% to 39.5% (p< 0.01). [18] The cost-effectiveness and accessibility of these molecular procedures, however, may be a limiting factor in the complementary method to the systemic approach to the diagnosis of pericardial effusion.

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. No statistical association is noted between elevated pericardial BNP levels and left ventricular systolic function. [19]

Other considerations

The accuracy and diagnostic value of biochemical and cell count analysis of pericardial effusions in distinguishing the various etiology of the effusion is lacking. A considerable overlap of several laboratory parameters creates a difficult approach in determining the causative agent to the effusion. [2, 3] Drainage of the pericardium in patients without hemodynamic compromise also has low diagnostic yield. [16, 17]

With the limited validity and diagnostic value of routine hematological and biochemical tests of pericardial fluid, results should be interpreted cautiously and used only as clinical correlates to patient’s overall presentation.

(Video) All about pericardium


How do you interpret pericardial fluid? ›

Physical characteristics – the normal appearance of a sample of pericardial fluid is straw-colored and clear. Abnormal results may give clues to the conditions or diseases present and may include: Milky appearance—may point to lymphatic system involvement. Reddish pericardial fluid may indicate the presence of blood.

What is abnormal amount of pericardial fluid? ›

Pericardial effusion is an acute or chronic accumulation of fluid within the pericardial space. Effusion can be transudative, exudative, or sanguineous. The pericardium has limited elasticity, and in acute settings, only 100 ml to 150 mL of fluid is necessary to cause cardiac tamponade.

How much pericardial fluid is normal? ›

Normally there is between 10–50 ml of pericardial fluid.

How is pericardial disease diagnosed? ›

Diagnosis. The diagnosis of acute pericarditis remains a clinical one based on history, physical examination, ECG and the echocardiogram. Other imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI) may be used in selected cases to investigate the pericardium.

What virus causes pericarditis? ›

Viral infection is the most common cause of acute pericarditis and accounts for 1-10% of cases. The disease is usually a short self-limited disease that lasts 1-3 weeks and can occur as seasonal epidemics, especially coxsackievirus B and influenza.

Is pericarditis a disease? ›

Pericardial disease, or pericarditis, is inflammation of any of the layers of the pericardium. The pericardium is a thin tissue sac that surrounds the heart and consists of: Visceral pericardium -- an inner layer that envelopes the entire heart.

Is a small amount of pericardial effusion normal? ›

Normally, there is a small amount of fluid between them. The fluid reduces friction between the two layers as they rub against each other during each heartbeat. In some cases, extra fluid can build up between these two layers leading to a pericardial effusion. A little fluid won't cause much of a problem.

What size is a significant pericardial effusion? ›

Echocardiography can provide an estimate of the size of effusions. Generally, small effusions cause an echo-free space in systole and diastole of less than 10 mm; moderate effusions, 10-20 mm; and large effusions, greater than 20 mm. The size of pericardial effusion is a powerful predictor of overall prognosis.

Is fluid around heart serious? ›

Pericardial effusion is a buildup of fluid in the space around the heart. It can happen for a wide range of reasons, including infections, injuries or other medical conditions. If the buildup is severe or happens quickly, it can compress your heart and cause cardiac tamponade, a life-threatening medical emergency.

How serious is fluid around the heart and lungs? ›

In this condition, the excess fluid within the pericardium puts pressure on the heart. The strain prevents the heart chambers from filling completely with blood. Cardiac tamponade results in poor blood flow and a lack of oxygen to the body. Cardiac tamponade is life-threatening and requires emergency medical treatment.

How is fluid around the heart treated? ›

Pericardiocentesis is a procedure done to remove fluid that has built up in the sac around the heart (pericardium). It's done using a needle and small catheter to drain excess fluid. A fibrous sac known as the pericardium surrounds the heart.

How long can a person live with fluid around the heart? ›

In chronic cases, it can last for more than 3 months. Some people with pericardial effusion may not show any symptoms, and doctors may discover the condition by chance — for example, if they notice fluid around the heart spaces in medical imaging that they have conducted for a different purpose.

Is pericarditis life threatening? ›

Pericarditis can range from mild illness that gets better on its own, to a life-threatening condition. Fluid buildup around the heart and poor heart function can complicate the disorder. The outcome is good if pericarditis is treated right away. Most people recover in 2 weeks to 3 months.

Is pericarditis serious? ›

Pericarditis causes chest pain and a high temperature. It's not usually serious, but it can cause serious health problems. Get medical advice if you have chest pain.

What color should pericardial fluid be? ›

Pericardial fluid is clear and pale yellow. Turbid fluid is indicative of infection or malignancy. Bloody fluid suggests malignant or tuberculous etiology. A milky appearance results from the presence of chylopericardium (6).

What do you test for pericardial fluid? ›

Your provider may order this test if you have signs of a heart infection ( myocarditis ) or a pericardial effusion (fluid buildup of the pericardium) with an unknown cause.

What is the important role of pericardial fluid? ›

The inner layer of the pericardium is attached to your heart muscle. There is a very small amount of fluid called pericardial fluid in the pericardial sac. This fluid helps to decrease friction between the pericardial layers. It also allows for smooth movement of the heart when it beats.

What is small pericardial effusion? ›

There is normally a small amount of fluid around the heart (small pericardial effusion). This is produced by the sac around the heart and is an important part of normal heart functioning. Excess fluid around the heart is known as a pericardial effusion.


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