C5 inhibitor best to regain kidney function in postpartum aHUS: Study
Treatment with or without plasma exchange better than supportive care
The use of a C5 inhibitor — with or without plasma exchange — was found to work better than supportive care to treat kidney problems in women who develop atypical hemolytic uremic syndrome (aHUS) as a complication of bleeding after giving birth, a study found.
However, the researchers noted that “recognizing this complication is crucial for the timely treatment and administration of C5 inhibitors, which may improve outcomes.” Two C5 inhibitors, Soliris (eculizumab) and Ultomiris (ravulizumab), are approved to treat aHUS.
“Patients treated with C5 inhibitors and/or plasma exchange had a better renal prognosis compared with patients who received supportive treatment alone,” the team wrote.
The scientists also observed that many of the women who developed aHUS had undergone a cesarean section, or experienced complications during pregnancy, such as miscarriage or preeclampsia — high blood pressure that can lead to organ damage.
Because some genetic mutations can predispose a person to aHUS, “genetic testing can be considered to detect hereditary [disease-causing] mutations, allowing for tailored counseling for the patient and her family regarding future pregnancies,” the team wrote.
The study, “Complement-mediated hemolytic uremic syndrome associated with postpartum hemorrhage: case series and systematic review of individual participant data,” was published in the journal Research and Practice in Thrombosis and Haemostasis.
Better outcomes seen for women treated with C5 inhibitor
The complement system is a part of the immune system that helps protect the body against infection. In aHUS, however, the complement system becomes overly active. This leads to the formation of blood clots inside small blood vessels that block blood flow to the body’s organs, causing them to become damaged.
While it can be challenging for doctors to diagnose it, aHUS sometimes develops during or just after pregnancy. It is thought that severe bleeding after delivery, known as postpartum hemorrhage, may trigger aHUS. However, this link has not been well studied.
To better understand if and how postpartum hemorrhage can trigger aHUS, a team led by researchers in Israel combined data from 33 studies involving a total of 48 women. The study also included data from three women who were diagnosed with aHUS at an Israeli medical center.
Nearly two-thirds of the women (62%) developed aHUS after a full-term pregnancy. More than half (51%) had a cesarean section for delivery, and many experienced complications during pregnancy. A total of 31% had preeclampsia, and 18% lost their baby via miscarriage.
Symptoms of aHUS typically began within 24 hours after delivery. Laboratory findings included high levels of lactate dehydrogenase, a marker of tissue injury or damage, and low numbers of platelets. Platelets are needed for the blood to clot. In aHUS, their numbers drop because they are being used to form blood clots.
Women treated with C5 inhibitors — medications that prevent the complement system from becoming overly active — with or without a blood-cleaning procedure called plasma exchange, proved to have the best recovery. Of the 23 women who received either Soliris or Ultomiris, 20, or 87%, regained normal kidney function.
C5 inhibitors and/or plasma exchange led to better [kidney] outcomes compared with supportive care.
A total of 11 women received plasma exchange without C5 inhibitors. Used on its own, plasma exchange helped seven (63%) of those women regain normal kidney function, while supportive care alone resulted in recovery for a smaller percentage (18%). The other women who only received supportive care either progressed to chronic kidney disease (70%) or died (12%).
These findings show that targeted treatment with C5 inhibitors leads to better results for women who develop aHUS as a complication of postpartum bleeding, according to the researchers.
The team noted that these medications “have been shown to be safe in pregnancy and the postpartum period, with no adverse effects reported in the fetus.”
Overall, for treatment, “C5 inhibitors and/or plasma exchange led to better [kidney] outcomes compared with supportive care,” the researchers wrote.
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