UPDATED April 2019: New Research Added
Click HERE to view the 24 August 2017 video regarding aHUS & pregnancy (Dr Craig Gordon, with preface by M Berry speaking about her patient experience), filmed at an event hosted by the aHUS Alliance Thrombotic Microangiopathies, Through the Lens of aHUS.
Atypical HUS is a complex and very rare disease, affecting an estimated 2 people per million population1 in the USA. Once thought to only affect the blood and kidneys of pediatric patients, aHUS has been diagnosed in people of all ages and it can impact multiple organs and body systems2. Following the 2015 international consensus of managing aHUS in children, we saw in 2016 the release of KDIGO guidelines for aHUS and other complement-mediated kidney disease. While the importance of those two documents for the diagnosis and management of patients with atypical HUS cannot be overstated, information about pregnancy and aHUS remains somewhat fragmented.
Not surprisingly, topics in women’s health face additional layers of questions and complexities in the face of an ultra rare disease diagnosis. Those dual pregnancy hallmarks of excitement but uncertainty are amplified for aHUS patients, since pregnancy and childbirth presents additional apprehension on multiple levels. Health of the mother and child remain the utmost concern, but additional considerations can be broad-reaching. For mothers who have already been diagnosed with atypical HUS, of high concern is passing along the condition to their children. Does having other, future pregnancies increase risk to the mother or the child’s health? How does aHUS affect family planning? Do hormonal fluctuations affect aHUS activity, frequency, severity, or episodic duration? For parents of female pediatric patients, fleeting thoughts stray to whether it ever will be medically advisable for their little girl to one day become a biological mother herself. It’s natural to express concern about family genetics and the possibility to pass along aHUS genetic variants. It’s understandable that families will have many questions about inherited aHUS (penetrance in aHUS families), which can be heightened during times of pregnancy.
Expectant mothers previously may have experienced a normal, healthy life only to be blindsided by having serious health concerns unexpectedly arise during their pregnancy or after just after delivery. “Pregnancy is a frequent triggering event in women: 20% of women with aHUS experience the disease, mostly the inaugural episode, at pregnancy, 80% of them during the post-partum period.”1 Imagine the shock and changed expectations as a normal pregnancy assumes life-threatening symptoms that mimic many other health conditions, making the diagnosis of atypical HUS confusing and difficult. Pregnant women and their families may have prepared their focus to celebrate a new life, only to be thrust into a tenuous situation that is so rare and unexpected that even their medical professionals seem hard pressed to decipher given such an unfamiliar medical situation.
It’s difficult to grasp the multitude of questions swirling through the minds of women diagnosed with aHUS, which likely increase from the moment their pregnancy is confirmed. The joys and trials of life do not stop once a rare disease diagnosis has been made. Concerns about coping with pregnancy and a newborn are compounded by patient realities such as support during illness and impact on work, lifestyle, and relationships. What options and provisions are in place for the baby if the mother becomes seriously ill during the pregnancy or after delivery? Depending on the region and healthcare system in their area, the primary doctor for an aHUS patient might be nephrologist, while others are monitored and treated by hematologists, immunologists, hem-onc subspecialists or others. For women who have already experienced aHUS activity, some will be assigned to a high-risk ob-gyn practice. Coordinating patient care for the pregnant aHUS patient and her child can bring hurdles and barriers to holistic and preventive care, as medical information and care plans must flow through one or more additional physicians. For those aHUS patients who become pregnant, fears about medication and treatment may come into play. How safe are the blood pressure drugs, or the infusions of complement inhibitor for the mother’s health? What’s the impact of plasmatherapy, plasmapheresis, infusions, and various drugs upon the unborn child? Is breastfeeding your newborn safe with the mother’s normal medical routine, or are adjustments required? What are the chances, and what is likely happen, if new medical issues crop up during the pregnancy, or after delivery? What can we expect for the immediate and long term health of the baby, and what concerns exist? Are there any actions to improve the medical condition and ongoing health of the developing child, the newborn, the growing child?
High blood pressure (hypertension) during pregnancy affects 6% to 8% of pregnant women. Pregnancy induced hypertension (PIH) can occur at various stages of pregnancy, have many causal factors, and can vary greatly in severity and duration. High blood pressure may develop after 20 weeks of pregnancy but resolve on its own after birth (gestational hypertension). Pre-eclampsia is a complication that generally occurs in the last trimester of pregnancy, affecting about 1 in 20 pregnancies. Symptoms of pre-eclampsia include a sudden and sharp rise in blood pressure, swelling (edema) in the face hands, and feet, and excess protein in the urine (albuminuria). A serious condition that can affect both mother and child, pre-eclampsia can occur during pregnancy or after delivery (postpartum), and having it once increases the risk that pre-eclampsia may affect future pregnancies as well. Of those women who develop pre-eclampsia, an estimated 15% can be affected by HELLP syndrome, a serious liver and blood clotting disorder marked by red blood cell destruction or Hemolysis (H), Elevated Liver enzymes (EL) and Low Platelet count or thrombocytopenia (LP). With red blood cell destruction, impaired blood clotting ability, and liver function issues, HELLP can threaten the mother’s life and potentially cause lifelong health problems. Sorting out these issues is difficult, even for medical personnel familiar with aHUS diagnosis and treatment.
Every mother, every family, every medical person shares that common desire to want things to go well for the pregnant mother and her child. What information is currently available about aHUS and pregnancy? Many knowledge gaps exist throughout the field of atypical HUS, but research regarding pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) has expanded in recent years. One French study3 looked at a sampling of 21 females with pregnancy-associated atypical hemolytic uremic syndrome within a larger cohort of 100 adult female aHUS patients, with 79% of P-aHUS presenting postpartum. In assessing the presentation and outcomes of P-aHUS patients, this clear and concise overview was provided into aHUS and pregnancy. “Forty-four patients with complement dysregulation (CFH = 24, CFI = 9, MCP = 4, C3 = 3, CFB = 2, >1 mutation = 3) had 103 pregnancies. Pregnancy was uneventful in 74.7% of patients and complicated with fetal loss in 4.8% of patients, preeclampsia in 7.7% of patients, and aHUS in 17.4% of patients. The risk of P-aHUS in these patients was highest during the second pregnancy”.
So where do we go from here, regarding questions and research about pregnancy and atypical HUS? “Pregnancy is an immunologically privileged condition, and levels of most complement proteins increase during pregnancy, subsequently falling after delivery.4” Increasing collaboration across scientific disciplines and specialities can only benefit the knowledge base and in turn improve patient outcomes. Research teams around the world are delving into the area of complement for a wide array of medical conditions, and this increased attention may stimulate advancements that could affect aHUS patients. As more exploration continues into immune system mechanics and crosstalk, information is likely to create deeper understand about aHUS as well. A recent aHUS Alliance article highlighted the crossover and innovation that seems poised to launch forward in 2017 and beyond, both for aHUS therapeutic R & D and for the management of this rare disease.
The aHUS Alliance of international patient associations remains committed to providing a platform for collaboration, facilitating shared information, developing relationships among stakeholders, and fostering opportunities that provide insight and engagement in the aHUS and rare disease arenas. Some efforts focus on providing better understanding and insight into the aHUS experience, such as the 2016 aHUS global poll. Other projects are more scholarly, such the Orphanet article on an innovative research partnership between the aHUS Alliance and the aHUS Global aHUS Patient Registry.
Above all, the aHUS Alliance provides information, connections, and insights to better understand the challenges of atypical aHUS. Look forward to the authentic voice of aHUS patients in our upcoming Rare Disease Day 28 Feb 2017 project about global aHUS research questions, from which viewers can learn directly from patient perceptions about research needs in areas such as pregnancy, family genetics, treatment access, and disease management.
L Burke, Feb 2017
(Updated Aug 2019)
Loirat, C and Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011; 6: 60. 2011 Sep 8. doi: 10.1186/1750-1172-6-60.
Hofer, H et al. Extra-Renal Manifestations of Complement-Mediated Thrombotic Microangiopathies. Front Pediatr. 2014; 2: 97. 2014 Sep 8. doi: 10.3389/fped.2014.00097
Fakhouri, F and Roumenina, L et al. Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations. J Am Soc Nephrol. 2010 May; 21(5): 859–867. doi: 10.1681/ASN.2009070706
Goodship THJ and Kavanagh D. Pulling the Trigger in Atypical Hemolytic Uremic Syndrome: The Role of Pregnancy. JASN May 1, 2010 vol. 21 no. 5731-732. doi:10.1681/ASN.2010030308
aHUS & Pregnancy – Videos
Atypical haemolytic uremic syndrome in pregnancy – Dr Kate Bramham (Thrombosis UK, 2018)
Updates on pregnancy associated aHUS from national centres – Prof David Kavanagh (Thrombosis UK, 2018)
Pregnancy & TMA: a Challenging Dilemma. Dr Craig Gordon, with aHUS patient experience intro by M Berry. TMA Symposium: Through the Lens of aHUS (Aug 2017) YouTube: Atypical HUS Clinical Channel
The Pregnancy Trigger. Dr Edwin Wong (aHUSUK, 2015 Conference)
Pregnancy and Atypical HUS. Dr. Michelle Hladunewich (aHUS Canada, 2015 Conference)
From Gestational Hypertension and Preeclampsia to Atypical Hemolytic Uremic Syndrome. (Dr. Han-Mou Tsai, IMAH Hematology Assoc. NY)
aHUS – Many Variants, Many Triggers. Dr D Kavanagh (aHUSUK 2015 Conference)
Links to More Research – aHUS & Pregnancy
Pregnancy Outcomes in Patients Enrolled in the Global aHUS Registry (Rondeau E et al, 2019)
Acute Kidney Injury in Pregnancy: The Changing Landscape for the 21st Century (Swati R and Belinda J, 2018)
Diagnostic dilemma: Severe thrombotic microangiopathy in pregnancy (Birkhoelzer S et al, 2017)
A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome (Huerta Ana et al, 2017)
Hemolytic Uremic Syndrome in Pregnancy and Postpartum (Bruel, Alexandra et al, 2017)
Pregnancy-Associated Atypical Hemolytic-Uremic Syndrome (Saad, A et al 2016)
Pulling the Trigger in Atypical Hemolytic Uremic Syndrome: The Role of Pregnancy (Timothy H.J. Goodship T. HJ and Kavanagh D, 2010)
Atypical uraemic haemolytic syndrome in pregnancy. Síndrome urémico hemolítico atípico en el embarazo (Pérez-Calatayud, A et al 2016)
How I treat thrombocytopenia in pregnancy. (Gernsheimer T. et al 2013)
Syndromes of thrombotic microangiopathy associated with pregnancy (George J, Nester C, and McIntosh J. 2015)
The Complement System and Adverse Pregnancy Outcomes (Regal J et al. 2015)
The Complement System and Preeclampsia (Regal JF et al, 2017)
Prepartum Eculizumab for prevention of atypical hemolytic uremic syndrome: A case report (Ardissino G et al, 2016)
Pregnancy-Associated Atypical Hemolytic Uremic Syndrome (aHUS), Treated with Eculizumab. (Mandala, EM et al 2014)
Early diagnosis and management of postpartum hemolytic uremic syndrome with plasma exchange. (Shrivastava, M et al 2011)
Advances in understanding of pathogenesis of aHUS and HELLP. (Fang CJ et al 2008)
Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn. (Hallstensen RF et al 2014)
READ the aHUS Alliance Interview with Dr. Fadi Fakhouri of France, and M Berry (aHUS patient)
“Good News” from talking about aHUS and Pregnancy (with Dr Fadi Fakouri)
Additional aHUS Article regarding aHUS and Pregnancy
Last Revised, August 2019