Management of Hemolytic Anemia in Wilson Disease
Patients with Wilson disease presenting with hemolytic anemia require urgent evaluation for liver transplantation, as this represents fulminant hepatic failure with near-universal mortality without transplantation. 1
Recognition of the Clinical Syndrome
Hemolytic anemia in Wilson disease is a medical emergency that signals fulminant hepatic failure with a characteristic constellation of findings: 1
- Coombs-negative hemolytic anemia with acute intravascular hemolysis features
- Coagulopathy unresponsive to parenteral vitamin K
- Rapid progression to renal failure
- Modest aminotransferase elevations (typically <2,000 IU/L) - this is a critical pitfall, as the relatively low transaminases often lead clinicians to underestimate disease severity 1
- Markedly low or normal alkaline phosphatase (typically <40 IU/L) 1
- Alkaline phosphatase to bilirubin ratio <2 1
- Female predominance (2:1 ratio) 1
The hemolysis results from massive copper release from necrotic hepatocytes, which directly damages red blood cells. 1, 2 Bilirubin levels are typically >10 mg/dL with a predominant indirect (unconjugated) fraction due to the hemolysis. 2, 3
Immediate Diagnostic Workup
When Wilson disease with hemolytic anemia is suspected: 1
- Serum copper - typically ≥200 μg/dL (≥31.5 μmol/L) 1
- 24-hour urinary copper - greatly elevated 1
- Serum ceruloplasmin - usually decreased, though predictive value is poor in acute liver failure 1
- Slit-lamp examination for Kayser-Fleischer rings - may be absent in 50% of cases, so absence does not exclude diagnosis 1
- Complete blood count with reticulocyte count, LDH, and haptoglobin to confirm hemolysis 2
- Liver function tests including bilirubin (fractionated), AST, ALT, alkaline phosphatase, INR 1
- Renal function (creatinine) as renal failure develops rapidly 1
Critical pitfall: Do not wait for copper studies to return before initiating treatment, as these results are often not available in a timely manner and diagnosis must rest on clinical features. 1
Immediate Management Algorithm
Step 1: Urgent Transplant Evaluation
List the patient immediately for emergency liver transplantation - this is the only life-saving treatment. 1 Medical therapy alone is ineffective in fulminant Wilson disease. 4, 5
Step 2: Bridge Therapies While Awaiting Transplant
Plasmapheresis (therapeutic plasma exchange) is the preferred bridge therapy: 1, 6, 5, 7
- Perform daily therapeutic plasma exchange using fresh frozen plasma as replacement fluid 5
- This significantly reduces serum copper, urinary copper excretion, and hemolysis 5
- Improves renal function and stabilizes clinical status 5
- More efficient at copper removal than albumin dialysis, though copper levels rebound between sessions 6
Alternative/adjunctive bridge therapy - Single Pass Albumin Dialysis (SPAD): 6, 7
- Can be used alone or in combination with plasma exchange 6
- Continuous SPAD for 28-32 hours can reduce serum copper by approximately 29-40% 6
- May be less efficient than plasma exchange but provides continuous copper removal 6
Combination approach (plasma exchange + SPAD) achieved 66.7% reduction in copper levels over 5 days in reported cases. 6
Step 3: Supportive Care
Renal protection: 1
- Hemofiltration or dialysis to protect kidneys from copper-mediated tubular damage 1
- Monitor creatinine closely as renal failure progresses rapidly 1
Avoid standard chelation therapy: 1
- D-penicillamine and trientine are ineffective in fulminant Wilson disease 4, 5
- The delay required for zinc-induced metallothionein increase makes zinc inappropriate for acute management 8
Do NOT transfuse blood products unless there is clinically significant bleeding, as coagulopathy reflects synthetic liver failure rather than consumptive coagulopathy. 3
What NOT to Do
- Do not attempt medical management alone - this is uniformly fatal without transplantation 4, 5
- Do not start chelating agents (penicillamine, trientine) as initial therapy for symptomatic patients with hemolysis 1, 8
- Do not use zinc acetate in acute presentations - it is contraindicated due to delayed onset of action 8
- Do not delay transplant evaluation while attempting medical stabilization 1
Prognostic Considerations
Without liver transplantation, mortality approaches 95-100%. 1, 4 The Nazer prognostic score (incorporating bilirubin, AST, and PT prolongation) identifies patients who will not survive without transplant - scores ≥7 predict non-survival. 1
Post-Transplant Management
After successful liver transplantation: 1