Earlier this year ,when the alliance was responding to the Rare Disease Day video questions , aHUS Patient Megan contacted the alliance having read the blog about pregnancy and aHUS (see blog here).
Megan offered to tell her story about getting aHUS , having children and being treated with eculizumab,as not much information existed about about these issues.
Professor Fadi Fakhouri of Nantes ,France,is well known for his research on P- HUS ,as aHUS secondary to pregnancy is known in medical circles. His group’s publication based on a study of 21 French aHUS patients, whose onset was precipitated by pregnancy , provided the best insight into the subject, albeit as Fadi admitted the numbers included in the research were too limited.
Recently Fadi has worked with another group of well known aHUS researchers in Italy , UK as well as France and studied what had happened to 87 women from the three countries who had experienced aHUS during pregnancy and child birth.
In August 2017 a major publication on this most “topical” of aHUS issues was published. ( see abstract here).
The alliance approached Megan and Fadi and asked if they would collaborate on an article for the alliance’s website and introduced them to each other . The result of that introduction is the following conversation between the two, as Megan tells her story and Fadi relates her experience to what is now known about P-HUS patients.
Hello! My name is Megan Berry.
Hi I am Fadi Fakhouri
Megan: In May of 2012, I had just miscarried a baby but I became pregnant a second time shortly after the miscarriage. My pregnancy was very high risk. I was told that I had Venus pools (pools of blood) behind the placenta, causing it to tear away from the Uterus. I was put on strict bed rest and told not to get up for anything except to use the bathroom.
Around 15 weeks into the pregnancy I had haemorrhaged and lost over 7 pints of blood. I was taken to the hospital where I was told it was normal and sent away. I returned that same night after having haemorrhaged a second time and immediately admitted. I was given a blood transfusion and ended up staying for 2 weeks.
Toward the end of my stay I met with an Oncologist. My mother told him we had a family history of TTP, since my paternal grandfather passed away of TTP. His younger sister had also passed away of the same thing. The oncologist immediately brushed it off and said he wanted to order a different test because he did not believe I had TTP.
Fadi: There is to date no simple test that helps tell the patient that he or she has or has not HUS. The diagnosis of HUS is made after a complex step-by-step approach that excludes other causes of thrombotic microangiopathy /TMA (clots in the small arteries of the kidney and other organs). However, this approach starts with the information doctors and nurses may collect by discussing with the patient and his/her family. And undoubtedly, family members are aware of severe diseases (as HUS is) affecting their relatives and siblings and a positive family history is a great help for the diagnosis of HUS. However, a positive family history is not a general rule and there may be some confusion about the precise type of thrombotic microangiopathy.
Megan: My oncologist ordered the ADAMSTS13 test. I was released from the hospital and 3 weeks later I had come back after a miscarriage with extreme abdominal pain. I was tested and results came back that my liver was about to shut down. I was then admitted and saw the oncologist again but he did not run any tests this time. He only gave orders to have me undergo a Plasma Exchange and then to receive Eculizumab.
Fadi- Diagnosis pregnancy-related HUS may be very challenging. When HUS occurs after delivery (post-partum) and the pregnancy has been uneventful, the diagnosis is rather straightforward. However, when HUS occurs during pregnancy or very close to delivery, the diagnosis may be difficult as several conditions may mimic HUS. The physician has to rule out these conditions by ordering some tests (such as ADAMTS13 assay) before diagnosing atypical HUS. This process may take a couple of days, and the physician may have to take medical decisions regarding treatments before all tests are completed.
Megan:During my Plasma Exchange, he came in to discuss with my father what my diagnosis was. Something had gone wrong with the test the first time so I was not able to be helped sooner. He explained that I had aHUS and explained what that meant. I do not know if I was genetically tested because a lot of my memories of that time are just pieces. I do however remember my doctor tell my dad I had factor H mutation. I have no evidence of that though. I began my treatments at the end of May 2012 I had been receiving them biweekly ever since.
Fadi : The first step in the treatment of a disease is to explain it to the patient, and this is particularly true for atypical HUS, a complex and rapidly progressing disease with limited and non-specific clinical symptoms. The occurrence of HUS during or shortly after pregnancy, or unfortunately sometimes after a miscarriage, is an additional source of stress and anguish for the patient and thus explanations are crucial.
Patients diagnosed with atypical HUS are usually tested for complement genes variants (also called mutations), but the genetic work-up may be lengthy and is not required for the diagnosis of atypical HUS and hence the start of treatment.
Patients with pregnancy-related HUS have the same frequency of complement gene variants and if untreated the same bad renal prognosis as any atypical HUS not related to pregnancy. Hence, pregnancy-related HUS is an atypical HUS that should be managed like any other atypical HUS. Available accumulating data indicate that eculizumab cures pregnancy-related HUS with the same efficacy noted in atypical HUS not related to pregnancy. Eculizumab has dramatically improved the outcome of pregnancy-related atypical HUS.
Megan: My doctor did tell me that having children would be out of the question because it would kill me, or the baby ,or both, if I became pregnant again.
Fadi: Yes pregnancy carries a high risk of atypical HUS occurrence or recurrence with ensuing damage to the mother’s kidney function but also to the baby’s health (prematurity, etc.). Nevertheless, the availability of eculizumab has changed the perspective of pregnancy for women with atypical HUS. Data available to date indicate that eculizumab use in pregnant women is safe and that the ratio benefit/risk tips clearly towards eculizumab use in pregnant women. Thus, pregnancy is usually no more contra-indicated in women with atypical HUS, pending that their renal function and blood pressure are acceptable.
Megan: So if I fast forward to late 2013, I found out I was pregnant again. I was so excited and scared at the same time. My doctor told me if would be my decision to terminate the pregnancy or to continue. I have strong views against abortion and I couldn’t justify terminating a baby. So, I chose to continue with the pregnancy and see what happens. I began seeing a high-risk OB and he worked closely with my Oncologist. I remained on biweekly infusions the entire pregnancy in addition to seeing a “high risk” doctor who worked very closely with my oncologist.
Fadi: Pregnancy in women with atypical HUS remains a high-risk pregnancy even in the era of eculizumab. For women not on eculizumab, close monitoring is required in order to rapidly diagnose atypical HUS recurrence and rapidly start eculizumab. Besides, eculizumab does not protect against other complications of pregnancies such as pre-eclampsia (high blood pressure and protein in the urine) or the worsening of renal function in patients who have chronic kidney disease as a consequence of atypical HUS. A multidisciplinary monitoring is fundamental and usually includes nephrologist/haematologist and obstetrician. Monitoring should not be stopped at the time of delivery as pregnancy-related HUS develop in more than half of the cases in the post-partum (up to 3 months after delivery).
Megan: I had a normal pregnancy and in July, 2014 I gave birth to a perfectly healthy baby boy. I did the same for my other two pregnancies. In 2015 I gave birth to another healthy boy and more recently, in 2016 I gave birth to my third healthy baby, a girl. My pregnancies were uneventful and all three babies were delivered by Caeserian Section. I did not want to stress my body any more than it already was with the pregnancies.
Fadi: This is an illustration of the fact that pregnancy may be uneventful in a patient with atypical HUS. These are good news for women with atypical HUS planning or starting a pregnancy. However, each pregnancy requires the same level of monitoring, because unfortunately, a woman can have three normal pregnancies and develop atypical HUS during or after the fourth pregnancy.
Megan : I remained on biweekly infusions of Eculizumab, and got Venofer due to low Iron.. All my labs remained constant and safe. I just recently started pushing my doses farther and am about to receive my second round of infusions every 6 weeks
Fadi: Eculizumab dose adjustments, especially longer intervals between infusions, are often requested by patients. Pregnant women however may require higher doses or shorter interval of eculizumab infusions due to the impact of pregnancy on the drug pharmacokinetics and the level of C5.
Megan: My babies are happy and healthy, my oldest is three , the middle one will be two in November and my youngest will be one after Christmas. None of them have been genetically tested yet, but I am in the process of having that done.
Fadi: Attitudes regarding screening of children of affected parents vary worldwide. However, one has to keep in mind that the detection of a variant in a complement gene is just a risk factor for atypical HUS and not, like in a conventional genetic disease, the certainty that the child will develop the disease. Genetic information may be helpful in healthy girls as they will be potentially exposed to a potent trigger of atypical HUS, pregnancy.
The aHUS alliance would like to thank Megan and Fadi for taking the time to have this conversation and marry up what an actual experience of aHUS and pregnancy is like and what is known from wide ranging research into the topic.
Megan appears in a video recorded ( click here ) at the TMA/aHUS symposium hosted by the aHUS Alliance on 24 August 2017 in Boston and which will be available, as an introduction to a clinical presentation on this topic, on our Atypical HUS Clinical Channel on YouTube. Click the link to learn more about the Thrombotic Microangiopathy Symposium: Through the Lens of aHUS.
Fadi is a member of the Scientific Advisory Board of the aHUS Registry and will be involved in yet another study of pregnancy and aHUS which has recently been approved by the SAB.
*the featured image is of Megan’s three children whom she talks about in this article.
Looking for research links regarding aHUS & pregnancy?
Click HERE for our aHUS Alliance overview with multiple resources.