What is the recommended diagnostic workup for ascitic fluid in a patient with new‑onset ascites?

Ascitic Fluid Workup for New-Onset Ascites

All patients with new-onset ascites require diagnostic paracentesis with a core panel of tests: cell count with differential, albumin (both ascitic fluid and serum to calculate SAAG), total protein, and bedside inoculation of at least 10 mL of fluid into blood culture bottles. 1, 2

Mandatory Core Tests

Cell Count with Differential

• Neutrophil count ≥250 cells/mm³ diagnoses spontaneous bacterial peritonitis (SBP) and mandates immediate empirical antibiotics without waiting for culture results. 1, 2
• Automated cell counting is accurate and provides rapid results, potentially replacing manual counts. 1
• This test must be performed even in asymptomatic patients, as SBP can be clinically silent. 3

Serum-Ascites Albumin Gradient (SAAG)

• Measure both serum albumin and ascitic fluid albumin simultaneously to calculate the gradient. 1, 3
• SAAG ≥1.1 g/dL indicates portal hypertension with 97% accuracy. 1, 2
• SAAG <1.1 g/dL points to non-portal hypertension causes (malignancy, tuberculosis, nephrotic syndrome, pancreatic disease). 1, 4
• The SAAG has replaced the outdated exudate/transudate classification system. 1

Total Protein Concentration

• Total protein <1.5 g/dL (or <15 g/L) identifies patients at high risk for developing SBP. 1, 2
• This parameter guides decisions about SBP prophylaxis in cirrhotic patients. 4
• Low protein ascites warrants closer monitoring and consideration of antibiotic prophylaxis. 4

Bacterial Culture

• Inoculate at least 10 mL of ascitic fluid into blood culture bottles at the bedside before any antibiotics are given. 1, 2
• Bedside inoculation increases culture sensitivity from approximately 50% to 80-90%. 3
• Starting antibiotics before obtaining cultures significantly reduces bacterial yield. 3

Conditional Additional Tests (Based on Clinical Suspicion)

When Suspecting Secondary Bacterial Peritonitis

• Order glucose, lactate dehydrogenase (LDH), and additional protein analysis. 1, 2
• Ascitic fluid carcinoembryonic antigen (CEA) >5 ng/mL or alkaline phosphatase >240 units/L suggests gut perforation into ascitic fluid. 1

When Suspecting Malignant Ascites (SAAG <1.1 g/dL)

• Send cytology and consider tumor markers such as CEA, EpCAM, CA 15-3, and CA 19-9. 2, 4
• Do not order serum CA-125—it is nonspecifically elevated by ascites from any cause and leads to unnecessary gynecologic referrals and potentially harmful surgeries. 4

When Suspecting Tuberculous Peritonitis

• Adenosine deaminase (ADA) levels <40 UI/L can exclude tuberculosis with high precision. 2
• Ascitic fluid smear for mycobacteria has approximately 0% sensitivity; fluid culture has only 50% sensitivity. 4
• Laparoscopy with biopsy and mycobacterial culture of tubercles provides the most rapid and accurate diagnosis. 4
• Consider in patients with recent immigration from endemic areas or HIV/AIDS. 4

When Suspecting Pancreatic Ascites

• Amylase levels typically >1000 UI/L or more than 6 times the serum amylase value are diagnostic. 2

When Suspecting Cardiac Contribution

• Measure serum BNP or NT-proBNP to distinguish cardiac versus hepatic disease contribution. 3
• Median pro-BNP is 6100 pg/mL in heart failure versus 166 pg/mL in cirrhosis. 1
• Physical examination for jugular venous distension helps differentiate alcoholic cardiomyopathy from alcoholic cirrhosis. 1

Safety Considerations for Paracentesis

• Routine prophylactic correction of coagulopathy with fresh frozen plasma or platelets is not recommended. 1, 3
• Coagulopathy should preclude paracentesis only when clinically evident fibrinolysis or disseminated intravascular coagulation is present (occurs in <1 per 1,000 procedures). 1
• There is no data-supported cutoff of coagulation parameters beyond which paracentesis should be avoided. 1
• Complications occur in only approximately 1% of patients (abdominal wall hematomas), despite 71% having abnormal prothrombin time. 1
• Severe hemorrhage occurs in only 0.2-2.2% of procedures with a death rate of 0.02%. 3
• Eight of nine bleeding complications in one large study occurred in patients with renal failure, possibly due to qualitative platelet abnormalities. 1

Critical Pitfalls to Avoid

• Do not delay paracentesis to correct coagulation parameters unless DIC or hyperfibrinolysis is clinically evident. 3
• Do not skip paracentesis even if the patient appears clinically stable—SBP can be asymptomatic. 3
• Do not order a battery of tests on every specimen; use an algorithmic approach based on initial results. 1, 5
• Do not assume a single etiology—actively search for mixed causes, particularly in patients with known cirrhosis who develop new ascites characteristics. 4
• Approximately 5% of patients have "mixed ascites" where cirrhosis coexists with peritoneal carcinomatosis or tuberculosis. 4

Clinical Context

• Cirrhosis accounts for approximately 75-80% of ascites cases in Western countries. 1
• The remaining 20-25% are due to malignancy, heart failure, tuberculosis, pancreatic disease, or other miscellaneous causes. 1
• The development of grade 2 or 3 ascites in cirrhotic patients is associated with poor prognosis (one-year mortality approximately 40%, two-year mortality approximately 50%), warranting consideration for liver transplantation. 1