What immediate laboratory tests should be ordered for a patient with suspected fulminant hepatitis?

Fulminant Hepatitis Laboratory Workup

For suspected fulminant hepatitis, immediately order prothrombin time/INR and assess mental status, as coagulopathy (INR ≥1.5) plus any degree of encephalopathy establishes the diagnosis and mandates ICU admission. 1, 2, 3

Immediate Diagnostic Laboratory Panel

The following tests must be obtained urgently to establish diagnosis, determine etiology, and guide management:

Core Diagnostic Tests

• Prothrombin time/INR – the single most critical test; INR ≥1.5 or PT prolonged by 4-6 seconds defines coagulopathy in fulminant hepatitis 1, 3
• Factor V level – superior prognostic indicator; levels <50% of normal indicate severe disease regardless of encephalopathy grade 4
• Complete blood count with platelets – essential for detecting hemolytic anemia (particularly in Wilson disease) and assessing bleeding risk 1
• Comprehensive metabolic panel including sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, glucose, creatinine, and blood urea nitrogen 1, 2
• Hepatic panel: AST, ALT, alkaline phosphatase, GGT, total and conjugated bilirubin, albumin 1, 2

Critical Monitoring Parameters

• Arterial blood gas and arterial lactate – lactate elevation indicates poor tissue perfusion and worse prognosis 1, 2
• Arterial ammonia level – correlates with encephalopathy severity and cerebral edema risk 1, 2
• Blood glucose – hypoglycemia is common and requires monitoring every 2 hours 2
• Serum sodium – must be maintained between 140-145 mmol/L to reduce cerebral edema risk 2

Etiologic Workup

Viral hepatitis serologies:

• Anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HEV, anti-HCV 1, 2
• Consider HSV-1/2 PCR if herpes hepatitis suspected 2, 5

Toxin and drug screening:

• Acetaminophen level – mandatory in all cases, as acetaminophen is now the leading cause of fulminant hepatitis in Europe and the United States 1, 2, 5
• Comprehensive toxicology screen 1, 2

Autoimmune markers:

• ANA, anti-smooth muscle antibody (ASMA), immunoglobulin levels 1, 2
• Important caveat: In acute severe autoimmune hepatitis, IgG is normal in 25-39% and ANA is absent/weak in 29-39%, so negative autoantibodies do not exclude the diagnosis 1, 3

Wilson disease screening (essential in patients <40 years):

• Ceruloplasmin level – typically low but can be normal 1, 2
• 24-hour urinary copper – elevated 1
• Serum uric acid and alkaline phosphatase-to-bilirubin ratio – ratio <2 is highly suggestive of Wilson disease 1, 3
• Look for the characteristic pattern: Coombs-negative hemolytic anemia, modest aminotransferase elevations (typically <2,000 IU/L), and markedly low alkaline phosphatase (typically <40 IU/L) 1, 3

Additional screening:

• Pregnancy test in all females of childbearing age 1, 2
• HIV status in at-risk patients, as coinfection affects prognosis 1
• Anti-HDV in patients with hepatitis B or history of injection drug use 1
• Amylase and lipase if clinically indicated 1
• Blood type and screen for potential transfusion or transplantation 1

Prognostic Laboratory Indicators

The following parameters guide transplant listing decisions:

• Prothrombin time/INR and Factor V – most reliable prognostic markers; Factor V <20% indicates extremely poor prognosis without transplantation 6, 4
• Total bilirubin – best indicator of severity alongside PT/INR 6
• Arterial lactate – persistent elevation suggests poor spontaneous recovery 2
• ALT levels – paradoxically, modest elevations (<2,000 IU/L) may indicate worse prognosis, particularly in Wilson disease and late-stage fulminant hepatitis 1, 3

Critical Pitfalls to Avoid

• Do not delay transfer to a transplant center while awaiting complete laboratory results; contact should occur immediately upon diagnosis 1, 2
• Do not assume autoimmune hepatitis is excluded by negative ANA or normal IgG; these are absent in up to 39% of acute severe presentations 1, 3
• Do not underestimate severity based on modest aminotransferase elevations, especially in Wilson disease where ALT is typically <2,000 IU/L despite fulminant presentation 1, 3
• Do not routinely correct coagulopathy with fresh frozen plasma or clotting factors unless active bleeding occurs, as this obscures accurate disease monitoring 2, 4
• Do not administer vitamin K and assume coagulopathy will correct; unresponsiveness to parenteral vitamin K is part of the diagnostic criteria 1, 3

Monitoring Frequency

Once diagnosis is established:

• Glucose monitoring every 2 hours at bedside 2
• Serial PT/INR, Factor V, and ammonia levels at least every 6-12 hours 2, 4
• Continuous assessment of mental status using standardized encephalopathy grading 2