What is the best course of action for a patient with epigastric abdominal pain and pruritus, elevated INR (International Normalized Ratio) on clopidogrel, and slightly elevated lipase?

Management of Epigastric Pain with Pruritus and Elevated INR

This patient requires urgent evaluation for intrahepatic cholestasis of pregnancy (ICP) or other hepatobiliary disease, with immediate measurement of serum bile acids and repeat liver function tests, followed by consideration of upper endoscopy to exclude peptic ulcer disease or gastric pathology. 1, 2

Critical Diagnostic Considerations

Pruritus as a Key Clinical Feature

The combination of new-onset pruritus of hands and feet with epigastric pain radiating to the right upper quadrant strongly suggests cholestatic liver disease, particularly if this patient is pregnant or has underlying hepatobiliary pathology. 1

• Pruritus in cholestatic disease typically precedes biochemical abnormalities by several weeks, meaning normal initial liver enzymes (ALT 33, AST 27, ALP 88) do not exclude the diagnosis. 1
• The pattern of palmar-plantar pruritus is particularly characteristic of cholestasis. 1
• Serum bile acids are the most sensitive test for cholestasis and must be measured urgently, as levels ≥10 μmol/L confirm the diagnosis even when other liver tests are normal. 1

INR Elevation Analysis

The INR of 1.5 on clopidogrel is unexplained and concerning, as clopidogrel does not affect INR. 2

• This elevation suggests either vitamin K deficiency from cholestasis (impaired bile acid secretion reduces fat-soluble vitamin absorption) or early hepatic synthetic dysfunction. 1
• Cholestyramine, if used for pruritus, can worsen vitamin K deficiency and should be avoided until INR is corrected. 1

Lipase Elevation Without Pancreatitis

The lipase of 88 is only mildly elevated and does not indicate pancreatitis in the absence of typical clinical features. 3

• Epigastric pain without nausea/vomiting and no tenderness on palpation makes pancreatitis unlikely. 1
• Elevated lipase can occur with cholestasis, infectious colitis, or medication effects without pancreatic inflammation. 3, 4
• The normal abdominal ultrasound further argues against pancreatitis. 1

Immediate Diagnostic Workup

First-Line Testing (Within 24-48 Hours)

Order serum bile acids immediately as the definitive test for cholestasis, with repeat measurement if symptoms persist and initial results are normal. 1

Repeat comprehensive liver panel including:

• ALT, AST, ALP, GGT (already done but need trending)
• Total and conjugated bilirubin (already done: total 7, conjugated 3)
• Albumin and INR (already done)
• Prothrombin time to confirm INR elevation 1

Exclude cardiac causes first with ECG and troponins, as myocardial infarction can present with epigastric pain, especially given the patient's cardiovascular history (stent, on clopidogrel). 2, 5

Second-Line Imaging

Upper endoscopy is indicated given the combination of epigastric pain radiating to RUQ, elevated lipase, and unexplained INR elevation. 1, 2, 5

• The patient's age, cardiovascular disease, and weight loss on therapy constitute alarm features requiring endoscopy. 1, 5
• Endoscopy should be performed with biopsy to exclude peptic ulcer disease, gastric malignancy, or duodenal pathology. 1, 6

CT abdomen with IV contrast should be considered if endoscopy is delayed or if biliary obstruction is suspected despite normal ultrasound. 1

• CT is superior to ultrasound for detecting subtle pancreatic or duodenal pathology. 1
• Neutral oral contrast (water) is preferred over positive contrast to assess mucosal enhancement and intraluminal bleeding. 1

Empirical Treatment Pending Results

Pruritus Management

Initiate ursodeoxycholic acid (UDCA) 10-15 mg/kg/day divided into 2-3 doses (typically 300 mg TID or 500 mg BID) for symptomatic relief while awaiting bile acid results. 1

• UDCA improves pruritus within 1-2 weeks even if cholestasis is not confirmed. 1
• If pruritus persists after 2 weeks, increase to maximum 21 mg/kg/day. 1
• Alternative agents include rifampin (combined with UDCA for refractory cases) or cholestyramine as second-line, though cholestyramine worsens vitamin K deficiency. 1

Acid Suppression

Start full-dose PPI therapy (omeprazole 20 mg daily or equivalent) for the epigastric pain component, as ulcer-like dyspepsia typically responds to acid suppression. 1, 5

• This addresses potential peptic ulcer disease while awaiting endoscopy. 1, 5
• Continue for 4-8 weeks and reassess response. 5

Vitamin K Supplementation

Administer vitamin K 10 mg orally or subcutaneously to correct the elevated INR, particularly if cholestasis is confirmed. 1

Critical Pitfalls to Avoid

Do not dismiss cardiac etiology - obtain ECG and troponins immediately given the patient's cardiovascular history and atypical presentation. 2, 5

Do not assume normal liver enzymes exclude cholestasis - bile acids are the definitive test and can be elevated when transaminases are normal. 1

Do not delay endoscopy in patients with alarm features - age, weight loss, and cardiovascular disease requiring antiplatelet therapy all mandate upper endoscopy. 1, 5

Do not attribute INR elevation to clopidogrel - clopidogrel does not affect INR, and this finding suggests either cholestasis with vitamin K malabsorption or hepatic dysfunction. 1

Do not use cholestyramine as first-line therapy - it worsens vitamin K deficiency and has limited efficacy compared to UDCA. 1

Follow-Up Strategy

Repeat bile acids and liver function tests in 1-2 weeks if initial results are normal but symptoms persist. 1

If bile acids remain normal after 4-6 weeks with persistent symptoms, refer to hepatology for further evaluation of non-cholestatic pruritus causes. 1

Perform endoscopy within 2-4 weeks regardless of bile acid results, given the alarm features and need to exclude structural pathology. 2, 5