What is the appropriate workup for a patient presenting with yellow‑tinged conjunctiva (jaundice)?

Workup for Yellow Conjunctiva (Jaundice)

Order total and fractionated bilirubin, complete blood count with peripheral smear, reticulocyte count, liver enzymes (AST, ALT, alkaline phosphatase, GGT), albumin, prothrombin time/INR, lactate dehydrogenase, and haptoglobin as your initial laboratory panel. 1, 2

Initial Laboratory Evaluation

The fractionated bilirubin is your critical first test because it determines whether you're dealing with unconjugated (indirect) or conjugated (direct) hyperbilirubinemia, which fundamentally changes your diagnostic pathway. 3, 2, 4

Essential First-Line Tests:

• Complete blood count with peripheral smear – identifies anemia, other cytopenias, and RBC morphology suggesting hemolysis 1
• Total and fractionated bilirubin – unconjugated predominates in hemolysis; conjugated suggests hepatobiliary disease 1, 2
• Reticulocyte count with reticulocyte index – elevated (>2.0) indicates increased RBC production from hemolysis or blood loss 1
• Liver enzymes (AST, ALT, alkaline phosphatase, GGT) – AST/ALT elevation suggests hepatocellular injury; alkaline phosphatase/GGT elevation indicates cholestatic/obstructive causes 5, 2
• Lactate dehydrogenase and haptoglobin – LDH elevated and haptoglobin decreased in hemolysis 1
• Albumin and prothrombin time/INR – assess hepatic synthetic function 2, 4

Algorithmic Approach Based on Laboratory Results

If Unconjugated Hyperbilirubinemia with Elevated Reticulocyte Count:

• This confirms hemolytic anemia 1
• Order direct Coombs test immediately to differentiate autoimmune from non-autoimmune hemolysis 1
• Assess hemodynamic stability; transfuse packed RBCs if hemoglobin <7 g/dL or if symptomatic with chest pain, dyspnea, or tachycardia 1
• The combination of sudden onset, pallor, jaundice, and tachycardia strongly favors hemolysis over primary liver disease 1

If Conjugated Hyperbilirubinemia with Elevated Alkaline Phosphatase:

• This suggests cholestatic/obstructive causes 1, 5
• Order abdominal ultrasound as your first-line imaging study 6, 5, 2
• Ultrasound findings of biliary dilation indicate need for advanced imaging with MRCP, CT, or ERCP 5, 7
• Consider choledocholithiasis (most common benign cause), biliary strictures, pancreatic adenocarcinoma, or cholangitis 6, 5

If Mixed Pattern with Elevated Transaminases (AST/ALT):

• This indicates hepatocellular causes 1
• Consider viral hepatitis (order hepatitis panel), autoimmune hepatitis, drug-induced liver injury, or alcoholic hepatitis 1, 3
• Obtain detailed medication history including over-the-counter drugs and herbal supplements, as drug reactions account for 0.5-7% of jaundice cases 1

Imaging Strategy

Abdominal ultrasound is your first-line imaging modality – it is the least invasive and least expensive method to differentiate extrahepatic obstructive from intrahepatic parenchymal disorders. 2, 4

If ultrasound is unrevealing or shows biliary dilation, proceed to:

• CT with IV contrast for suspected malignancy or complex biliary pathology 2
• MRCP for detailed biliary tree visualization without invasive procedures 7, 2
• ERCP if therapeutic intervention is anticipated 5

Critical Pitfalls to Avoid

• Never assume hepatobiliary disease without checking reticulocyte count – sudden onset with pallor and tachycardia in younger patients strongly favors hemolysis 1
• Do not delay transfusion in symptomatic patients – fatigue with tachycardia indicates significant anemia requiring urgent intervention 1
• Do not overlook sepsis – it is the most common cause of jaundice in U.S. studies (22-27%) and can cause both hemolysis and hepatic dysfunction 1
• Always obtain comprehensive medication history – drug-induced liver injury is frequently missed 1
• Urine bilirubin testing can rapidly confirm conjugated hyperbilirubinemia if laboratory results are delayed 3

When to Consider Advanced Testing

If the etiology remains unclear after initial laboratory testing and imaging:

• Liver biopsy may be required to establish diagnosis, prognosis, and management 2, 8
• Autoimmune antibody assays if autoimmune hepatitis is suspected 4
• Additional cancer screening if malignancy is a concern 4