Follow up to: 21-year-old with liver failure and hemolytic anemia
A couple of weeks ago I posted a case of a 21-year-old young woman who presented with acute liver failure and hemolytic anemia. As suggested by one of the emails we received, this young lady had Wilson’s disease and the combination of liver failure and hemolytic anemia is a giveaway presentation of this rare disease.
In our case, the presentation was quite classic as described in the literature and was recognized quickly by our hepatologist. Her ceruloplasmin level (the copper carrying protein) was slightly low but was likely elevated due to an acute phase reaction. Her urine and plasma copper were quite high (24 hour urine collection was 27180 mcg [normal 3-35 mcg]). She underwent 4 consectutive days of plasma exchange with FFP as the replacement product and underwent an uncomplicated liver transplantation. The following chart shows the drop in creatinine following plasmapheresis (extending the span of the red bracket) and the date of liver transplant (black arrow).
Her INR and bilirubin dropped similarly, although not quite back to normal before the transplant. Because the clinical team suspected ongoing hemolysis and coagulopathy, she received a new liver when one became available. As you can see in the H&E and trichrome stains of the native liver, there is clear cirrhosis. Her hepatic parenchymal copper content (by ICP/MS) was 1103 mcg/g dry weight, which is “strongly suggestive of Wilson’s disease.” A level of <40-50 mcg/g dry weight almost always excludes the disease.
I came into contact with this case on my Blood Bank rotation because we were asked in consultation to assess her for plasmapheresis. Wilson’s disease is not included as an indication in the ASFA (American Society for Apheresis)’s recommendations for therapeutic apheresis, but a few case series have shown its effectiveness, especially in cases showing fulminant liver failure and hemolytic anemia. Thus, it should probably be a category III indication (diseases with anecdotal benefit but for which there is limited data or conflicting results from published clinical trials). The thought is that excessive copper accumulates in hepatocytes due to inherited autosomal recessive mutations in a copper transport gene, ATP7B, that codes for a P-type ATPase. When this accumulation reaches some threshold, the liver begins to fail as hepatocytes die and release copper into the circulation, which damages erythrocytes through membrane damage or enzyme disruption. This is thought to be the mechansim behind the hemolysis partly because of the strong, direct association of levels of serum copper and the severity of hemolysis.
Plasmapheresis effectively removes the toxic levels of copper in the circulation to disrupt the hemolytic cycle, most importantly sparing the kidneys of irreversible damage. In some cases in the literature, plasmapheresis has been used effectively to obviate the need for liver transplantation, but in most of the cases it serves as a bridge to stabilize the patient in anticipation of a donor liver. Many of these patients are female and have fit into an age range of 16-21, as was true in our case.
Random fact: if you are looking for copper in your diet, you may find it in these foods: shellfish, nuts, chocolate, mushrooms, organ meats…among others. See, you learn something new every day!
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