Pregnancy repeatedly triggered aHUS in woman with C3 variant, case finds
Early Soliris, plasma infusion, and dialysis were part of successful treatment
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A woman with a history of blood abnormalities and kidney problems during and after pregnancies was eventually diagnosed with postpartum-triggered atypical hemolytic uremic syndrome (aHUS) in a case study.
After aHUS was strongly suspected, she began Soliris (eculizumab) treatment and ultimately achieved complete remission.
The researchers recommended that clinicians distinguish postpartum aHUS from other conditions with overlapping symptoms to prevent treatment delay.
The study, “Recurrent Postpartum Atypical Hemolytic Uremic Syndrome Caused by a C3 Pathogenic Variant: A Case Report,” was published in the International Journal of Women’s Health.
aHUS can be difficult to distinguish from other pregnancy complications
aHUS is marked by blood clot formation in small blood vessels, driven by uncontrolled activation of the complement cascade, part of the immune system. Its three hallmark symptoms are hemolytic anemia (destruction of red blood cells), thrombocytopenia (low platelet counts), and acute kidney failure.
Most people with aHUS have mutations in genes involved in regulating the complement cascade. But genetic changes alone typically are not enough to trigger the disease. An additional event, such as pregnancy or the postpartum period, often is involved.
Postpartum aHUS can look similar to several other conditions, including preeclampsia (high blood pressure and high levels of protein in urine), HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), and thrombotic thrombocytopenic purpura (TTP). That overlap can make diagnosis difficult and delay treatment.
Unlike preeclampsia and HELLP syndrome, postpartum aHUS does not typically resolve after delivery and can progress rapidly to kidney failure without timely treatment.
In this case, a woman experienced recurrent blood and kidney problems during and after pregnancy, but wasn’t diagnosed with postpartum aHUS until after her third pregnancy.
Near the end of her first pregnancy, 12 years earlier, she developed hypertension (high blood pressure), high levels of protein in her urine, and peripheral edema, or swelling in the extremities. After a cesarean section, the problems resolved without treatment.
Nine days after giving birth to her second child, eight years earlier, she experienced nausea, vomiting, and hypertension. Tests showed hemolytic anemia, low platelet counts, acute kidney injury, and low levels of two complement proteins, C3 and C4.
She was diagnosed with thrombotic microangiopathy, a group of conditions in which small blood vessels become blocked by microscopic blood clots. She then received three sessions of plasma exchange, a treatment in which doctors remove plasma (the liquid part of blood) and replace it with healthy plasma. Her kidney function and blood measures fully recovered.
Earlier episode was initially linked to possible lupus nephritis
The researchers also suspected lupus nephritis, kidney inflammation caused by the autoimmune disease lupus. Despite C3 deposits on kidney biopsy and low blood C3 levels, her urine protein remained normal and her kidney function remained stable during eight years of follow-up.
During her third pregnancy, at age 35, she developed dizziness and hypertension before delivering by cesarean section. Two days after delivery, her condition worsened, with severe dizziness, nausea, marked hypertension, and dark-colored urine. Blood tests revealed low platelet counts and worsening kidney function.
A blood smear showed moderate anisocytosis (variation in red cell size) and schistocytes (fragmented red cells). Testing ruled out TTP, while tests for autoimmune disease were negative. However, doctors still considered possible lupus nephritis because of her prior history.
Complement testing showed signs of complement activation, including low C3 and factor I, along with a markedly elevated soluble membrane attack complex. Genetic testing then detected a pathogenic variant in the C3 gene associated with aHUS. Imaging showed enlarged kidneys. Heart structure was normal, although imaging also showed a small amount of fluid around the heart and minimal changes in the lungs.
While aHUS was strongly suspected, the team was still uncertain about a possible autoimmune disease, including lupus nephritis. She therefore received intravenous steroids. She also received plasma infusions to replenish complement regulatory proteins while awaiting Soliris treatment.
Within 24 hours of admission, she began treatment with Soliris, an antibody therapy approved for children and adults with aHUS. She also received treatment to lower blood pressure and prevent infection and osteoporosis (weakened bones).
Kidney and blood problems worsened before recovery
Her condition initially worsened despite treatment. Her platelet count and hemoglobin fell further, while kidney function worsened. She also developed symptoms of heart failure and uremia (a buildup of waste products in the blood due to kidney failure), including chest tightness, shortness of breath, nausea, and vomiting.
She received furosemide to reduce fluid buildup and dialysis to treat heart failure and remove waste products. Her condition then improved progressively, and after about one month her platelet count, kidney function, hemoglobin, and lactate dehydrogenase, a marker of cell damage and hemolysis, had returned to normal.
With treatment, her vital signs stabilized, her heart failure resolved, and she no longer needed dialysis. At the most recent follow-up, seven months after the episode, she remained in complete remission with stable kidney function and no evidence of hemolysis or thrombocytopenia. She continued to receive maintenance Soliris therapy, with no adverse events or relapses reported.
“This case highlights that C3 variant-mediated aHUS can be repeatedly triggered by pregnancy,” the researchers concluded. “Clinicians should distinguish postpartum aHUS from preeclampsia, HELLP syndrome, and TTP to prevent treatment delay.”
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