What further workup is recommended for a patient with cirrhosis, splenomegaly (enlarged spleen), and uptrending leukocytosis (elevated white blood cell count) despite 4 days of broad-spectrum antibiotics?

Workup for Uptrending Leukocytosis in a Patient with Cirrhosis and Splenomegaly

A diagnostic paracentesis should be performed immediately to rule out spontaneous bacterial peritonitis (SBP) as the cause of uptrending leukocytosis in this cirrhotic patient with splenomegaly, despite negative cultures from previous workup. 1

Initial Diagnostic Approach

• Perform a diagnostic paracentesis to evaluate for SBP, which can present with minimal symptoms in cirrhotic patients and is a common cause of leukocytosis 1
• Collect ascitic fluid for cell count, culture, and biochemical analysis with bedside inoculation into blood culture bottles to increase culture sensitivity to >90% 1
• Obtain simultaneous blood cultures to increase the possibility of isolating a causative organism 1
• Consider diagnostic thoracentesis if pleural effusion is present, as spontaneous bacterial empyema (SBE) can occur with or without SBP 1

Additional Infection Workup

• Repeat complete blood count with differential to track leukocytosis progression and evaluate for bandemia (>5% bands), which may indicate ongoing inflammatory response 2
• Perform urinalysis and urine culture to rule out urinary tract infection, which is the second most common infection in cirrhotic patients (22% of infections) 1
• Obtain chest X-ray to evaluate for pneumonia, which accounts for approximately 19% of infections in cirrhotic patients 1
• Consider skin examination for soft tissue infections, which are also common in cirrhosis 1, 3

Evaluation for Hypersplenism

• The patient's significant splenomegaly (19 cm) strongly suggests hypersplenism as a contributing factor to the leukocytosis 4, 5
• Hypersplenism in cirrhosis with portal hypertension can cause alterations in blood cell counts, including leukocytosis or leukopenia 4
• Review peripheral blood smear to evaluate for characteristic changes of hypersplenism and to rule out hematologic malignancies 4
• Consider bone marrow examination if peripheral smear shows abnormal cells or if there's suspicion of a primary hematologic disorder 2

Evaluation for Non-Infectious Causes

• Consider persistent inflammation-immunosuppression and catabolism syndrome (PICS), which can present with prolonged leukocytosis in hospitalized patients with tissue damage rather than active infection 2
• Evaluate for drug-induced leukocytosis, including review of all medications (particularly beta-lactam antibiotics which can affect white blood cell counts in cirrhotic patients) 6
• Monitor for development of eosinophilia (>500 cells/mm³), which may indicate PICS or drug reaction rather than bacterial infection 2

Management Considerations

• If SBP is confirmed (PMN count >250 cells/mm³ in ascitic fluid), initiate appropriate antibiotic therapy immediately 1
• For patients with SBP and signs of renal impairment, administer albumin (1.5 g/kg at diagnosis and 1 g/kg on day 3) to reduce the risk of hepatorenal syndrome 1
• Consider broadening antibiotic coverage if there's no response to current therapy, as multidrug-resistant organisms are increasingly common in cirrhotic patients 1, 3
• Avoid aminoglycosides due to high risk of nephrotoxicity in cirrhotic patients 3, 6

Special Considerations

• Recognize that typical symptoms of infection may be absent or minimal in patients with cirrhosis 1, 7
• Be aware that bacterial infection should be suspected in any cirrhotic patient with unexpected clinical deterioration 7
• Consider that the systemic inflammatory response and classical symptoms of infection are often weakened in cirrhosis 7
• If all infectious workup remains negative, consider partial splenic artery embolization as a therapeutic option for hypersplenism-related hematologic abnormalities in appropriate candidates 4, 5