Wilson’s Disease (WD) is an autosomal recessive disorder affecting copper metabolism, leading to copper buildup in organs like the brain, liver, and kidneys. It usually begins with liver copper accumulation, presenting as acute hepatitis and hepatomegaly. Hemolytic anemia is a rare complication of WD. We report the case of a previously healthy 18-year-old female who presented with hemolytic anemia, rapidly progressing to fulminant hepatic failure, necessitating a liver transplant due to undiagnosed WD. This case highlights the critical importance of early diagnosis, as timely treatment can be lifesaving.
Wilson’s disease (WD), or hepatolenticular degeneration, is an inherited disorder affecting copper metabolism, leading to copper buildup in the liver, brain, and kidneys. WD has a broad age range for initial presentation, necessitating its inclusion in differential diagnoses across ages. Most patients experience neurological and hepatic symptoms. Severe hemolytic anemia and fulminant hepatic failure as initial WD presentations are rare, often delaying diagnosis and treatment. Untreated, this presentation has a 95% mortality rate, with an emergent liver transplant as the only definitive treatment.
We present an 18-year-old healthy female with severe refractory hemolytic anemia, suspected to have fulminant hepatic failure secondary to WD. She was quickly transferred to a liver transplant facility and underwent an emergent transplant. This case underscores the importance of prompt and accurate diagnosis, as delays can lead to decompensated hepatic failure and increased mortality risk.
Case Presentation:
A previously healthy, 18-year-old Caucasian female presented to an emergency department in West Virginia with a five-day history of nausea, vomiting, and right upper quadrant abdominal pain. She was noticeably jaundiced and reported dark, cola-colored urine. She had no prior hospitalizations or medical issues, and her family history was negative for liver disease or other serious illnesses.
Initial laboratory findings suggested hemolytic anemia with a hemoglobin level of 6.6 g/dL (normal: 13.4-17.5 g/dL), total bilirubin of 15.7 mg/dL (normal: 0.3-1.2 mg/dL), and direct bilirubin of 8.2 mg/dL (normal: 0.1-0.4 mg/dL). Lactate dehydrogenase (LDH) was 307 U/L (normal: 135-225 U/L), reticulocyte count was elevated, and haptoglobin was low. The Coombs test was negative.
Her transaminases were elevated: aspartate aminotransferase (AST) was 118 U/L (normal: 8-40 U/L), alanine transaminase (ALT) was <5 U/L (normal: 4-36 U/L), and alkaline phosphatase (ALP) was significantly low at 18 U/L (normal: 40-120 U/L). The international normalized ratio (INR) was prolonged at 2.85 (normal ≤1.1), indicating compromised hepatic function.
Within 24 hours, the patient’s condition worsened, with confusion and somnolence. Her total bilirubin increased to 45 mg/dL, and LDH rose to 836 U/L. Hemoglobin remained low despite multiple packed red blood cell (pRBC) transfusions.
Admission tests revealed a high serum copper level at 2.03 mg/dL (normal: 0.7-1.4 mg/dL), a low ceruloplasmin level of 17 mg/dL (normal: 20-100 mg/dL), and increased urine copper excretion at 11,406 µg/day (normal: 20-50 µg/day).
The combination of hemolytic anemia and fulminant hepatic failure, along with specific markers (low ceruloplasmin, elevated urine copper, and low ALP levels) led to a diagnosis of WD. This was further confirmed by an ALP/bilirubin ratio >4 and an AST/ALT ratio >2.2, indicating fulminant hepatic failure from WD.
Due to her critical condition and risk of life-threatening complications, she was urgently transferred to a transplant-capable facility, where she received a liver transplant four days after admission.
Discussion:
Wilson’s disease (WD) presenting initially as fulminant hepatic failure and severe hemolytic anemia is rare. However, the American Association for the Study of Liver Diseases guidelines suggest considering Coombs-negative hemolytic anemia with acute intravascular hemolysis when suspecting fulminant hepatic failure due to WD. Typically, Coombs-negative hemolysis results from oxidative damage to erythrocytes triggered by high copper concentrations. Patients may also present with dark urine and renal failure. This presentation is serious and necessitates urgent liver transplantation, which is the only intervention that stops hemolysis and provides a cure.
This case involves a young, otherwise healthy female who initially presented with severe, persistent, Coombs-negative hemolytic anemia. Rapid diagnostic workup and subspecialty consultations enabled her physicians to attribute her acute liver failure and hemolytic anemia to WD quickly.
Treatment limitations included the patient’s rapid progression to fulminant hepatic failure and delays in laboratory results for copper and ceruloplasmin levels. Her diagnosis was not confirmed until the second day of hospitalization.
Despite these challenges, the patient was promptly transferred to a transplant-capable facility, received a liver transplant, and survived. As of June 2024, the patient remains alive and well.
Conclusions:
This case underscores the importance of considering Wilson’s disease (WD) in the differential diagnosis of fulminant and acute hepatic failure, particularly in young patients. Hemolytic anemia, although less common, can be an initial presentation and may complicate and delay diagnosis and treatment due to the patient’s rapidly worsening condition. Maintaining a high index of suspicion and promptly obtaining serum and urine copper and ceruloplasmin measurements can facilitate early diagnosis and lifesaving interventions, such as liver transplantation. This case highlights the need for increased physician awareness of the diverse presentations of WD and the critical importance of swift diagnosis to prevent rapid patient deterioration.
Possible References Used
