When Jaundice Tells Two Stories: Chronic Hemolysis Overwhelming the Liver

Every so often a case comes along that refuses to fit into our tidy categories.

An adult male presented to the emergency department with profound weakness and striking jaundice. His hemoglobin was 3.7 g/dL, yet he was mentating normally and his lactate was within range — clear evidence of physiologic compensation.

The chemistry panel featured a total bilirubin >70 mg/dL, direct fraction ≈ 40 mg/dL, with biliary dilation on CT abdomen/pelvis.

On the hematology side, LDH was elevated, haptoglobin undetectable, and the antibody screen revealed a warm autoantibody.

Parsing the Pattern

At first pass, this looks like hemolysis. Severe anemia, high indirect bilirubin, low haptoglobin, elevated LDH — all the hallmarks are there. But a direct fraction comprising more than half the total complicates the picture: pure hemolysis shouldn’t yield that much conjugated bilirubin.

That left two possibilities running in parallel:

1. Primary biliary obstruction (choledocholithiasis, mass, or stricture).

2. Secondary cholestasis from sustained hemolytic load — the liver overwhelmed by the ongoing destruction and turnover of red cells.

   
   

The patient’s stability pointed toward chronicity. A hemoglobin of 3.7 g/dL with preserved mentation doesn’t happen overnight. This was the physiology of slow, compensated hemolysis finally tipping into hepatic decompensation.

Hemolysis Meets Cholestasis

In warm autoimmune hemolytic anemia (AIHA), extravascular destruction can be relentless but insidious. Over weeks to months, bilirubin production rises and the liver adapts — upregulating conjugation and secretion. Eventually, canalicular transport capacity becomes the rate-limiting step. The bile becomes supersaturated with bilirubin diglucuronide, predisposing to pigment stone formation and sometimes true biliary obstruction.

At that point, the chemistry shifts: direct hyperbilirubinemia emerges, not because the process stopped being hemolytic, but because the liver and biliary tree have been drawn into the downstream pathology. The biliary dilation on CT fits perfectly — not as a primary obstruction, but as a secondary phenomenon of chronic pigment overload.

Testing in Context

The serologic workup tied it together.

• Positive DAT with warm autoantibody → ongoing immune hemolysis.

• Elevated LDH and absent haptoglobin → hemolytic physiology confirmed.

• Normal lactate and preserved mental status → chronic compensation.

  
  

The picture that emerged was not an acute biliary event but chronic AIHA complicated by secondary cholestasis, possibly with choledocholithiasis from pigment stones.

Biliary Workup

MRCP revealed subtle hilar ductal thickening, raising concern for an underlying cholangiocarcinoma. Yet the broader picture didn’t cooperate: tumor markers and an autoimmune cholangiopathy panel were unremarkable.

To clarify, an ERCP was performed — several darkly pigmented stones were extracted, and brushings of the bile duct were sent for cytology. No malignant cells were identified.

The findings reinforced the idea of secondary biliary involvement rather than a primary neoplasm. The obstruction appeared mechanical but self-limited, the likely consequence of pigment stone formation in the setting of chronic hemolysis. It was a reminder that when the biliary tree becomes the downstream casualty of hematologic disease, imaging can mimic malignancy and tumor markers can mislead.

Takeaway

This case reminds me how rarely biology stays within our categorical lines. Direct hyperbilirubinemia does not exclude hemolysis when destruction has been sustained enough to overwhelm excretory capacity.

It’s the intersection we rarely see illustrated in textbooks: where hemolysis becomes overwhelming, the liver becomes a bottleneck, and “prehepatic” injury evolves into a mixed cholestatic picture.

Sometimes the right answer really is “both.”