Rare Disease Report

Does Eculizumab Play a Role in Treating Pregnancy-Associated Atypical Hemolytic-Uremic Syndrome?

DECEMBER 29, 2014
Christina Loguidice

Atypical hemolytic–uremic syndrome (aHUS) is a rare disease that causes platelet thrombi to form in the small blood vessels in the kidneys and other vital organs, restricting or blocking blood flow and increasing the risk of stroke, myocardial infarction, renal failure, and death. Three major features characterize aHUS: hemolytic anemia, thrombocytopenia, and renal failure. aHUS can have genetic, acquired, or idiopathic etiologies; however, genetic mutations of the alternative complement pathway are recognized as the cause in more than 60% of patients.[1] Although aHUS can occur at any age, including in unborn infants, it disproportionately affects children. In the setting of pregnancy, aHUS has been reported to occur in approximately 1 in 25,000 pregnancies, with mother and fetus having poor outcomes.[2]
Historically, the only treatment for aHUS was plasma therapy, including rapid plasma exchange or fresh frozen plasma infusions, but this treatment did not result in full remissions and did not target the genetic mutations that are often the underlying cause of the disease. In 2011, the US Food and Drug Administration (FDA) approved Soliris (eculizumab) as the first pharmacological treatment for aHUS, including in children, and it remains the only approved agent for this condition.[3]
Eculizumab is a monoclonal antibody that binds to the complement protein C5 with high affinity, thereby inhibiting complement-mediated thrombotic microangiopathy in patients with aHUS.[4] Although the agent is approved for adults and children, it has not been adequately studied in pregnant women. Because mouse models showed increased rates of developmental abnormalities and an increased rate of dead and moribund offspring at doses 2 to 8 times those given to humans, it has a category C drug classification. Subsequently, eculizumab’s prescribing information advises avoiding this agent unless “the potential benefit justifies the potential risk to the fetus.”[4] Several such cases have been reported, showing favorable results in pregnant patients whose disease did not remit following plasma therapy.[2,5] 
The most recently reported case was presented at Kidney Week 2014.[4] It involved a 30-year-old woman who was 22 weeks pregnant. She had a medical history of hypertension and systemic lupus erythematosus and presented with a 1-week history of abdominal pain and leg swelling. Her laboratory findings showed abnormal hemoglobin levels and platelet counts and impaired kidney function. aHUS in the setting of volume overload was suspected, prompting initiation of plasma exchange, hemodialysis, red blood cell transfusion, and intravenous steroids. After 2 weeks of treatment, the patient remained anuric and had elevated lactate dehydrogenase (LDH) levels and thrombocytopenia. Eculizumab was initiated and resulted in rapid recovery of her platelet count, LDH levels, and hemoglobin levels, and it was well tolerated by the patient and her fetus. The baby was delivered via Cesarean section three weeks later, and it was found to be healthy despite being premature. The patient was discharged from the hospital on eculizumab and a prednisone taper. Because the treatment was well tolerated and resulted in cessation of the disease process, the presenters support the use of eculizumab as a treatment for pregnancy-associated aHUS, but note that timing of this therapy needs to be elucidated to avoid hemodialysis.   
Another case reporting good results with eculizumab for aHUS in a pregnant woman was reported in 2013 in Obstetrics and Gynecology.[5] This case involved a 26-year-old woman with a history of aHUS, which relapsed at 17 weeks gestation during her first pregnancy. She underwent multiple plasma exchanges, but the disease persisted. She was started on eculizumab at 26 weeks gestation. This treatment was well- tolerated, led to remission, and enabled her to deliver a healthy neonate. Based on these findings, the authors conclude that “eculizumab may be useful for the treatment of [aHUS] during pregnancy.”


1. Nester CM, Thomas CP; American Society of Hematology. Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated? http://asheducationbook.hematologylibrary.org/content/2012/1/617.full. Published December 8, 2012. Accessed December 10, 2014.
2. Aly AAA, Abdulhak AAB, Ansari MW, et al. Eculizumab in Pregnancy-Associated Atypical Hemolytic Uremic Syndrome. Presented at: Kidney Week 2014; November 11-16, 2014; Philadelphia, PA. Abstract PUB240.
3. US Food and Drug Administration. FDA approves Soliris for rare pediatric blood disorder. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm272990.htm. Published September 23, 2011. Accessed December 10, 2014.
4. Soliris [package insert]. Alexion Pharmaceuticals, Inc., Cheshire, CT; 2014. http://alexionpharma.com/Documents/soliris_pi-4-2014.aspx. Accessed December 10, 2014.
5. Ardissino G, Wally Ossola M, Baffero GM, Rigotti A, Cugno M. Eculizumab for atypical hemolytic uremic syndrome in pregnancy. Obstet Gynecol. 2013;122(2 Pt 2):487-489.

Did you know…

  • aHUS has an estimated prevalence of 1 in 100,000 persons.
  • Pregnancy may be the trigger in 10% of patients with aHUS.
  • The risk for pregnancy-associated aHUS is highest during the second pregnancy.
  • Women with complement dysregulation have a 20% risk for pregnancy-associated aHUS, and any pregnancy in these women should be closely monitored.
Source: http://www.ncbi.nlm.nih.gov/20301541

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