Plasma exchange therapy, Ultomiris manage woman’s aHUS
Case report shows benefit of early identification, treatment
Early plasma exchange therapy followed by Ultomiris (ravulizumab) treatment successfully managed atypical hemolytic uremic syndrome (aHUS) in an 83-year-old woman, according to a report from Japan.
The woman started showing symptoms of aHUS after a bone fracture. Genetic testing revealed she had a mutation in the CFI gene, which encodes a protein that’s part of the complement cascade, a component of the immune system that is deregulated in people with aHUS.
“Our case serves as a crucial example demonstrating how prompt identification and appropriate management can lead to better patient outcomes,” the researchers wrote.
The report, “A Case of Atypical Hemolytic Uremic Syndrome With a Complement Factor I Mutation Triggered by a Femoral Neck Fracture,” was published in Nephrology.
In aHUS, the overactivation of the complement cascade leads to the formation of blood clots in small blood vessels, which can block blood flow and cause organ damage.
Gene mutations vary by region, race
Three main aHUS symptoms mark the disease: hemolytic anemia, which occurs when red blood cells are destroyed faster than are produced; thrombocytopenia, or low numbers of platelets that normally help the blood to clot; and acute kidney failure, which occurs when the kidneys are unable to function normally.
Most people with aHUS have mutations in genes that regulate the function of the complement cascade. The frequency of these mutations varies with region and race. Mutations in the CFI gene, which encodes a protein called complement factor I, are present in 4% to 8% of patients in Europe, but had not been reported in Japan.
The researchers described the case of an 83-year-old woman in Japan with a CFI mutation who developed aHUS after a bone fracture. The woman fell at home and was admitted to the hospital with a fracture in her left thigh bone.
At her initial evaluation, she was found to have acute kidney failure, high blood pressure, and low levels of hemoglobin (the protein that carries oxygen in red blood cells) and platelets, consistent with aHUS. She also had high levels of creatinine, a marker of kidney dysfunction, and lactate dehydrogenase, a marker of cell and tissue damage, in the blood.
Further testing excluded autoimmune conditions and other diseases as a cause for her illness.
Genetic testing revealed the presence of a novel mutation in one copy of the CFI gene, which was considered to be likely disease-causing, confirming the aHUS diagnosis. The researchers said she was “the first Japanese patient with aHUS associated with a CFI mutation.”
The woman’s kidney function deteriorated while she was hospitalized, and she was started on hemodialysis, a treatment used to filter waste and excess fluids from the blood when the kidneys can no longer do so. She was also started on plasma exchange, in which plasma, the liquid part of blood, is removed and replaced to temporarily provide a patient with complement regulatory proteins that may be dysfunctional in people with aHUS.
These treatments led to a reduction in blood creatinine levels, accompanied by an increase in platelet counts.
The woman underwent eight plasma exchange and nine hemodialysis sessions, until days 14 and 18 of hospitalization, respectively. On day 35, she received her first dose of Ultomiris, an antibody-based therapy that blocks complement activation by targeting the C5 complement protein, which further increased her platelet counts.
On the 49th day of hospitalization, she received her second dose of Ultomiris. Subsequently, her hemoglobin levels remained stable, and creatinine levels decreased.
The woman could not stand due to a previous fracture in the right thigh bone. Doctors decided not to perform surgery, because it was not expected to significantly improve her daily functioning.
She was transferred to a rehabilitation hospital, where she continued receiving maintenance doses of Ultomiris every eight weeks, with no episodes of aHUS recurrence over the next two years.
“Early treatment with plasma exchange and [Ultomiris] resulted in successful treatment in this case,” the researchers wrote, adding that “it is essential to suspect aHUS and initiate treatment early when thrombocytopenia with haemolytic anaemia, high serum lactate dehydrogenase levels, or organ dysfunction is present, such as in cases of acute kidney injury.”
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