Is hemolytic anemia associated with Wilson's disease?

Hemolytic Anemia in Wilson's Disease

Yes, hemolytic anemia is definitely associated with Wilson's disease and can be the initial presenting symptom in some cases. According to the European Association for the Study of the Liver (EASL) clinical practice guidelines, Coombs-negative hemolytic anemia may be the only initial symptom of Wilson's disease in some patients 1.

Prevalence and Presentation of Hemolytic Anemia in Wilson's Disease

• Hemolysis occurs in approximately 5-20% of patients with Wilson's disease presenting with liver disease, as shown in multiple studies 1
• In one series, hemolysis was a presenting feature in 25 out of 220 cases (12%) 1
• Hemolysis can present in different patterns:
  • Single acute episode
  • Recurrent episodes
  • Low-grade chronic hemolysis 1

Pathophysiology and Clinical Significance

• Hemolytic anemia in Wilson's disease is typically Coombs-negative 1
• Marked hemolysis is commonly associated with severe liver disease 1
• The mechanism involves:
  • Release of large amounts of stored copper from damaged liver cells
  • Direct toxic effect of free serum copper on erythrocyte membranes 2
  • Further aggravation of hemolysis by released copper 1

Clinical Scenarios and Severity

1. Isolated presentation: In a Japanese series of 283 patients, only three presented with acute hemolysis alone 1

2. With jaundice: One quarter of patients presenting with jaundice also had hemolysis 1

3. With liver failure: Hemolytic anemia can be part of fulminant Wilson's disease presentation, which is characterized by:

   • Acute liver failure
   • Hemolysis
   • Sometimes renal failure 3, 4
   • Deep jaundice
   • Low hemoglobin
   • Low cholinesterase
   • Mildly increased transaminases
   • Low alkaline phosphatase 1

4. During pregnancy: Acute liver disease and hemolysis can occur during delivery, mimicking HELLP syndrome 1

Diagnostic Implications

• In young patients with unexplained hemolysis, Wilson's disease should be considered in the differential diagnosis 5
• Low-grade hemolysis may be present even when liver disease is not clinically evident 1
• Some patients with neurologic presentations of Wilson's disease report previous transient episodes of jaundice, likely due to hemolysis 1
• Blood smear may show stippled red cells in some cases 2

Treatment Considerations

• In cases of fulminant Wilson's disease with hemolysis, liver transplantation is often necessary as medical therapy may be ineffective 3
• Plasmapheresis can be used as a bridge to liver transplantation by:
  • Reducing serum copper
  • Decreasing hemolysis
  • Helping prevent renal tubular injury from copper and copper complexes 4
• Standard copper chelation therapy with D-penicillamine and zinc is effective for long-term management once the acute phase is stabilized 5

Key Clinical Pearls

• Hemolytic anemia may be the first manifestation of Wilson's disease even before obvious liver or neurological symptoms appear 6, 5
• The combination of hemolytic anemia and liver dysfunction in a young patient should prompt consideration of Wilson's disease 5
• Untreated Wilson's disease with fulminant hepatic failure carries a mortality rate of approximately 95%, emphasizing the importance of early diagnosis 7