What is the diagnosis and management for a patient presenting with jaundice, severe anemia, elevated Prothrombin Time (PT) International Normalized Ratio (INR), and cholelithiasis?

Diagnosis: Acute Cholangitis with Severe Hepatic Decompensation

The most likely diagnosis is acute cholangitis secondary to choledocholithiasis, complicated by severe hepatic dysfunction and coagulopathy, requiring urgent biliary decompression and intensive supportive care. 1

Clinical Reasoning

This constellation of findings—jaundice, severe anemia, elevated PT/INR, and cholelithiasis—points to biliary obstruction with secondary hepatic injury rather than primary hepatocellular disease:

• Choledocholithiasis is present in approximately 10% of patients with gallstone disease and represents a potentially life-threatening condition requiring biliary decompression in nearly all cases 1
• The elevated INR in the context of biliary obstruction reflects both hepatic synthetic dysfunction and vitamin K malabsorption due to cholestasis, rather than isolated liver failure 1
• Severe anemia with jaundice suggests either hemolysis (contributing to unconjugated hyperbilirubinemia) or chronic disease with acute decompensation 1, 2

Immediate Diagnostic Workup

Laboratory Assessment Priority

• Fractionated bilirubin (conjugated vs. unconjugated) to differentiate obstructive from hemolytic causes 1, 2, 3
• Complete blood count with peripheral smear to evaluate for hemolysis (schistocytes, spherocytes, elevated reticulocyte count) 2, 3
• Liver enzymes with specific attention to AST/ALT ratio and alkaline phosphatase/GGT elevation 1, 4
  • Cholestatic pattern: alkaline phosphatase >3x normal with modest transaminase elevation suggests obstruction 1
  • AST/ALT ratio >2 with modest elevations (<400 IU/L) suggests alcoholic hepatitis if relevant history 1
• Blood, urine, and ascites cultures (if ascites present) to exclude cholangitis/sepsis 1
• Serum creatinine and lactate to assess for hepatorenal syndrome or septic shock 1, 5

Imaging Strategy

Right upper quadrant ultrasound is the mandatory first-line imaging modality to confirm biliary obstruction and assess for:

• Dilated intrahepatic or extrahepatic bile ducts (>6 mm CBD diameter) 1, 4
• Presence and location of stones 1
• Gallbladder wall thickening or pericholecystic fluid suggesting cholecystitis 1

If ultrasound confirms dilated ducts but the distal CBD is not well visualized (sensitivity for distal CBD stones only 22.5-75%), proceed directly to ERCP for both diagnosis and therapeutic intervention rather than additional imaging 1

MRCP should be reserved for cases where ultrasound shows no ductal dilation but clinical suspicion remains high, or when the level/cause of obstruction is unclear and ERCP may not be immediately therapeutic 1

Severity Stratification

Assess for Severe Disease Requiring ICU-Level Care

Calculate Modified Discriminant Function (mDF) or MELD score to stratify mortality risk:

• mDF = 4.6 × (PT in seconds - control PT) + serum bilirubin (mg/dL) 1, 5
  • mDF ≥32 indicates severe disease with 40-50% mortality without treatment 1
• MELD score >20-30 predicts high 90-day mortality 1, 5

Monitor for hepatic encephalopathy every 4-6 hours using West Haven criteria, as progression to grade III-IV dramatically changes management and prognosis 5

Serial monitoring every 12-24 hours of INR, bilirubin, creatinine, and mental status is essential to track trajectory 5

Management Algorithm

Immediate Stabilization (First 6 Hours)

1. Administer vitamin K 10 mg IV/subcutaneously to address potential malabsorption-related coagulopathy, though response may be limited if hepatic synthetic function is severely impaired 6

   • Do NOT prophylactically correct INR with FFP unless active bleeding or pre-procedural, as INR monitoring guides prognosis 5

2. Transfuse packed red blood cells to hemoglobin >7 g/dL (higher target if active ischemia or ongoing bleeding) 5

3. Initiate broad-spectrum antibiotics immediately if fever, leukocytosis, or hemodynamic instability present (presumed cholangitis until proven otherwise) 1

4. Aggressive fluid resuscitation while monitoring for volume overload, maintaining serum sodium 140-145 mmol/L to prevent cerebral edema if encephalopathy develops 5

Definitive Biliary Intervention

ERCP with sphincterotomy and stone extraction is the mainstay of therapy for choledocholithiasis, with 90% success rate 1

Timing of ERCP:

• Within 24 hours if cholangitis suspected (Charcot's triad: fever, jaundice, right upper quadrant pain) 1
• Within 48-72 hours for obstructive jaundice without infection 1
• If complete stone extraction not possible, placement of internal plastic stent ensures adequate biliary drainage 1

Percutaneous transhepatic biliary drainage is reserved for ERCP failure or anatomic contraindications 1

Critical Pitfalls to Avoid

• Do not delay biliary decompression for "optimization" of coagulopathy—the obstruction itself perpetuates the coagulopathy 1, 5
• Beware of concurrent hemolysis masking the degree of conjugated hyperbilirubinemia—fractionated bilirubin is essential 1, 2
• In elderly patients (>65 years), major complication rates from ERCP sphincterotomy approach 19% with 7.9% mortality—consider initial stent placement without sphincterotomy 1
• Rising MELD score despite supportive care warrants urgent liver transplant center consultation, even if encephalopathy not yet present 5

Escalation Triggers for Transplant Evaluation

Contact liver transplant center if:

• Progression to hepatic encephalopathy grade III-IV 5
• INR continues rising beyond 3.0 despite vitamin K and biliary decompression 5
• Development of metabolic acidosis (pH <7.30) or lactate >3.5 mmol/L 5
• Worsening renal function with oliguria or rising creatinine 5
• MELD score exceeds 30-35 with clinical deterioration 5