Delay in aHUS Diagnosis Linked to Woman’s Previous Cancer

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by Margarida Maia PhD |

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A diagnosis of atypical hemolytic uremic syndrome (aHUS) was delayed in a woman with a history of advanced, but treated, cancer due to several confounding factors partly related to that cancer, according to a case report from the U.S.

While the woman also had anemia and poor kidney function, two hallmarks of aHUS, the diagnosis was not made until her kidneys continued to worsen.

After starting on Soliris (eculizumab), her condition improved. “A timely diagnosis is necessary to initiate the correct treatment,” the researchers wrote.

The report, “Atypical hemolytic uremic syndrome in a patient with metastatic peritoneal serous carcinoma: A case report,” was published in the journal Cureus.

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Thrombotic microangiopathies like aHUS are characterized by the destruction of red blood cells (hemolytic anemia), low platelet counts (thrombocytopenia), and the formation of blood clots that clog small blood vessels.

When this occurs in the kidneys, it makes them work harder to remove waste products and excess fluid from the blood. This can ultimately lead to kidney failure.

As the symptoms of aHUS overlap with those of other thrombotic microangiopathies, it may be difficult to reach a proper diagnosis in a timely manner.

“On a broader note, complicated patients present a challenge for clinical diagnosis as they have multiple confounding factors that suggest a different diagnosis,” the researchers wrote.

“All resources and testing available to clinicians must be considered, as these tools help to definitively confirm the diagnosis and provide insight into further management of patients,” they wrote.

Researchers detailed the case of a 61-year-old woman who was diagnosed in 2015 with peritoneal serous carcinoma of the ovary, which is a tumor arising from the tissue that covers organs in the abdomen. The cancer was metastatic, meaning it had already spread elsewhere.

She underwent surgery to remove as much of the tumor as possible, and was treated with chemotherapy. Doctors also performed paracentesis to remove excess fluid from her abdomen.

Shortly after her last dose of chemotherapy in late 2019, the woman went for a follow-up examination at Holy Cross Hospital in Fort Lauderdale, Florida.

She complained of shortness of breath and fatigue. Blood tests showed she had thrombocytopenia and low levels of hemoglobin, a protein in red blood cells that is responsible for oxygen transport.

She was given a red blood cell transfusion and transferred to the emergency department, where she was found to have hypertension, or high blood pressure. Hypertension can occur when the kidneys are not working well and there is a buildup of waste products and fluid in the blood.

A chest X-ray revealed an enlarged heart, and further tests found the presence of proteins and red blood cells in her urine, indicative of kidney damage. Blood tests revealed anisocytosis, unequally sized red blood cells, and schistocytes, fragmented red blood cells.

Based on these findings, she was diagnosed with hemolytic anemia.

Her anemia and kidney function continued to worsen. She underwent another red blood cell transfusion and was offered dialysis to help remove waste products and excess fluid, but refused the procedure.

Intravenous steroid treatment did not lead to improvements, and she was started on daily plasmapheresis — a form of treatment that involves replacing a person’s plasma, the liquid non-cell portion of blood.

Blood tests to measure the amount or activity of complement proteins showed low levels of C3, C4, and CH50. Complement proteins work with the immune system to help defend the body against threats like viruses and bacteria. Mutations in genes encoding complement proteins can cause aHUS.

Further tests revealed normal activity of ADAMTS13, a protein that can help distinguish aHUS from thrombotic thrombocytopenic purpura — another disease characterized by the formation of blood clots in small blood vessels, in which ADAMTS13 is lacking.

Since lab tests had not returned to normal despite treatment, the woman was again hospitalized in early 2020 looking pale and with generalized edema (swelling), which doctors attributed to her poorly working kidneys.

Based on further test results, an aHUS diagnosis was made. Genetic testing identified a known disease-causing mutation in a gene providing instructions for making thrombomodulin, a protein involved in blood clotting.

The woman was started on Soliris and dialysis. She also received the meningococcal vaccine as Soliris may increase the risk of meningococcal bacterial infections.

Her condition improved and she was discharged from the hospital. “At the time of writing [of the report], this patient is currently doing well,” the researchers wrote.

“This patient’s worsening anemia was complicated by her cancer diagnosis and her chemotherapeutic regimen, causing delays in diagnosis and treatment,” they wrote, adding that “this was further compounded by the patient’s initial refusal of dialysis during her initial hospitalization.”