Woman’s Case Highlights Need for Better aHUS Diagnostic Criteria

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by Vanda Pinto PhD |

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The case of a woman with unusual symptoms for atypical hemolytic uremic syndrome (aHUS) — including normal hemoglobin levels and mildly low platelet counts — highlights the need for better and more clear diagnostic criteria for this condition, according to researchers.

The goal is to ensure that patients can receive a prompt and adequate diagnosis so as to start treatment as soon as is possible, the team said.

“[aHUS] can be challenging to diagnose,” especially if key symptoms are not severe when the disease first starts, according to the researchers, who noted that there are “no clear diagnostic criteria for aHUS.”

“It remains a diagnosis of exclusion,” the team wrote, adding, however, that it is “vital” to diagnose aHUS promptly since swiftly starting treatment can lead to better patient outcomes.

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The patient’s case was described in the study, “Rare Presentation of Atypical Hemolytic Uremic Syndrome in an Adult,” published in the journal Cureus.

aHUS belongs to a group of diseases called thrombotic microangiopathies or TMAs, in which blood clots form in small blood vessels, causing organ damage. There are three main symptoms that characterize aHUS and are used as diagnostic criteria: hemolytic anemia, which occurs when red blood cells are destroyed, low platelet counts known as thrombocytopenia, and acute kidney failure.

Clinicians sometimes have difficulties in diagnosing aHUS since its symptoms are similar to those of other TMAs, such as typical hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP).

But despite having similar initial symptoms, these disorders have different underlying causes. aHUS is caused by the abnormal activation of the complement cascade — a part of the immune system that helps defend the body against disease-causing agents. Meanwhile, typical HUS is mainly caused by an infection with Shiga toxin-producing bacteria. Conversely, TTP is caused by the lack of a protein involved in blood clotting, called ADAMTS13.

A correct diagnosis is important since clinical trials have demonstrated that Soliris (eculizumab), a complement inhibitor marketed by Alexion Pharmaceuticals, is effective for treating aHUS.

In this report, a team of researchers from the Quillen College of Medicine at East Tennessee State University described the case of a 59-year-old woman with aHUS who did not present typical symptoms.

The patient reported experiencing nausea, vomiting, stomach pain, and diarrhea for two days after eating at a local gathering. She did not have fever or chills and showed no signs of gastrointestinal tract bleeding. Her family took her to the emergency department when she began having hallucinations and other mental disturbances.

Her lab tests revealed she had a higher-than-normal number of white blood cells (15,900 cells per microliter or mcl; normal range: 4,500–11,000 cells/mcl). Her platelet counts were mildly low (139,000 platelets/mcl; normal range: 150,000–400,000 platelets/mcl) and her hemoglobin levels were normal (12.9 g/dL; normal range: 12.3–15.3 g/dL).

She also had acute kidney injury and a CT scan showed signs of inflammation in her colon.

Based on these findings, the researchers suspected that an infection by the bacteria Clostridium difficile (C. difficile) was causing her symptoms and she was subsequently treated with antibiotics and hemodialysis for kidney failure. However, her stool analysis came back negative for C. difficile, Shiga toxin, and other microbes.

Her mental status deteriorated, and she developed anemia with a hemoglobin level of 9.8 g/dL, as well as worse thrombocytopenia, with a platelet count of 66,000 platelets/mcl. Further blood tests revealed the presence of red blood cell fragments (schistocytes), a feature of TMA, as well as high levels of lactate dehydrogenase (LDH), a marker of tissue damage, and low haptoglobin, an indicator of red blood cell destruction.

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The woman was then diagnosed with TMA and started on plasma exchange — a procedure in which a patient’s plasma, or the liquid portion of blood, is removed and replaced — and anti-inflammatory steroids.

Further testing showed that she was negative for ADAMTS13 deficiency, which ruled out TTP. Typical HUS also was ruled out because the test for Shiga toxin had been negative. In addition, no secondary causes of TMA were found, and the levels of C3 and C4, two complement system-related proteins, were low.

Overall, the findings pointed toward aHUS, and plasma exchange was discontinued after four cycles.

“While plasma exchange is still the first-line treatment for TMA, including TTP, it is less effective in aHUS than TTP, as it does not address the underlying complement dysfunction,” the researchers wrote.

The patient then started weekly treatment with Soliris, and although her anemia, platelet counts, and LDH levels improved at first, they eventually worsened again. Her kidney function did not improve and she still needed hemodialysis. After four doses of Soliris, she refused further treatment and chose to enroll in hospice care.

“[aHUS] can be challenging to diagnose, especially if the anemia and thrombocytopenia are not profound at presentation,” the team wrote, noting the need for improved diagnostic criteria.

“It is vital to diagnose aHUS promptly as prompt initiation of [Soliris] can lower mortality and morbidity,” they wrote, adding that “aHUS should be suspected in a patient presenting with TMA once Shiga toxin HUS, secondary HUS, and TTP are ruled out.”