Post-Event Update:
Presentations were videotaped, and appear on our
Atypical HUS Clinical Channel as the key asset of
2017 aHUS Awareness Day (24 Sept).
Our sincere thanks to all participants & attendees at the Thrombotic Microangiopathy Symposium: Through the Lens of aHUS.
WATCH the TMA Symposium Presentations:
Atypical HUS Clinical Channel – YouTube: TMA Boston (playlist)
Awaiting the start of the TMA symposium to get underway at the Joseph B Martin Conference Centre at Harvard Medical School.
Good mix of delegates including clinicians, pharma industry, and patients/carers.
Dr Joseph Bonventre, Chief of the Renal Unit and Director of Bio engineering at Brigham and Women’s Hospital, opens the symposium by welcoming delegates.
Len Woodward of the aHUS alliance welcome delegates to the symposium giving some background to the alliance , the challenges of aHUS as a rare disease ,particularly diagnosis, and the pivotal moment that TMA is identified which if soon enough not only makes the leap to a HUS diagnosis more likely but improves outcomes for patients.
Dr Andrew Seidlecki then explained the format of the conference and the part of the patient voice in the conference as a lead into the medic talks.
The three patients Emma Megan and Michael then introduced themselves and explained when they heard of the condition TMA.
Dr Joel Krier then talked about a study he had undertaken of an aHUS family using whole genome sequencing. The patient family had been identified by his group as having no known cause of their illness and then undertook DNA testing . The patient had presented with “painful blue toes”. A range of diseases were thought possible but it was not definite.
A number of genes were suspicious but one variant on C3 in the complement system was of much interest and a novel mutation was a candidate.
The evidence was built by comparing with other reports in the literature and comparing notes with other researchers.
The conclusion was that the illness fell within the spectrum of aHUS. It was considered that treatment with eculizumab had some potential. He finished by asking if anyone knows of any other family around the world with similar aHUS issues he would be pleased to hear about them to help gather more evidence and firm up conclusions.
The next talk kicks off with patient speakers talking about their symptoms prior to diagnosis. Their experiences were contrasting yet there were parallels.
Dr Jean Francis then spoke about the challenge of diagnosing aHUS and offering a multidisciplinary approach to diagnosis of TMA.
He outlined an atypical HUS presentation but then added the enormous complications caused by the many other manifestations of TMA overlapping and different ,so there are so many possibilities.
He described the development of the Boston TMA Diagnosis Team.
Beginning with a description of a timeline of case for a 64 year old woman . This was discussed in a kind of “grand rounds” but after 35 days the outcome was fatal. The decision was made to change the protocols at the hospital learning from the days taken and the range of participants.
The key goal was to improve patient outcomes.
It involved support and interventions 24/7 with primary care and ER. Work was shared through the team with simultaneous rather than sequential action leading to joint decision making. This was set into an algorythim, and making hospitals everywhere in the catchment area aware through an intense communications programme.
The re-engineering of the process reduced the timeline from over 30 days to no more 5 days and the post change patient outcomes improved considerably.
It also led to a research collaboration on TMA both within the hospital and elsewhere.
Lack of awareness requires continual education to sustain awareness and also sharing and availability registry data given the rarity of the condition.
Patient Megan talked about her journey with pregnancy related HUS. From the outset of the pregnancy , through a miscarriage, the onset of aHUS , commencing on eculizumab. Then had three pregnancies which were successful with C Sections deliveries and there are now three healthy babies.
Dr Graig Gordon then talked about P-HUS and its challenging dilemma.
He begun with a case study to illustrate the pathogenisis of TMA in pregnancy and treatment using eculizumab.
Then he described AKI and its timing in pregnancy showing across the TMA syndromes precipitated by pregnancy.
The TMA syndromes included TTP as well as aHUS and how time of onset in pregnancy is a possible indicator of which syndrome it is likely to be.
Focussing on a very recent report from Europe ( Bruel et al ) on 87 women about 18% of all females in the registries.
58% of aHUS ocured in first pregnancy and almost all in the post partum period.
There was some treatment with eculizumab but the jury is out on how long that treatment is for.
He then reported on the use of eculizumab in PNH patient pregancy indicating its a safe and effective.
Counselling of patients was important, risk of recurrence is uncertain. Mutations , previous experience and family history are important factors.
Patients speakers then talked about the number of different clinical professionals they have seen during their illness. The range was considerable.
Dr Nathan Connell gave an haemotologists view of aHUS care.
Structuring a talk around the four key triggers of TMA including Complement mediated HUS.
TTP is the prime thought when TMA presents.
He then went through a history of HUS and said that aHUS got its name first in the Central African Journal of Medicine in 1965.
He outlined the pathophysiology of the various TMAs and proposed that the Modified Ham Test might become a game changer when it comes to aHUS diagnosis blood test.
Once diagnosis of TMA is made, PEX must start before TTP is ruled out. This can be done in 24 hours! Eculizumab if needed can then begin.
How to do better earlier diagnosis , availability of complement inhibitors . Thinking about Q of L and financial burdens . More health care education.
Patients speakers then gave their thoughts on when they thought they felt better on treatment. there were considerable differences between those not receiving eculizumab and those who did.
Dr Andrew Seidlecki then talked on the subject on what to treat and how to treat it.
Starting with eculizumab a treatment of choice for aHUS.
He illustrated the development of drug process from trials to approval and what information is in the public domain in particular Clinicaltrials.Gov. He listed the trials taking place to treat Complement and TMA indications some of which may be applicable to aHUS.
Drugs of interest include OMS721, ALXN 1210, Avacopan ALN-CC5 Coversin Avacincaptad.
He mentioned the ” lack of footprint” for the developing world and included the video Kamal Shah’s talk to United Nations NGO for Rare Diseases.
A panel discussion followed between doctors and patients on topics such as fatigue or whether aHUS should be so nephrocentric. And patient advocate Jeff read a testimonial from a family who lost a family member to aHUS and showed some images of other aHUS patients who have lost their lives.
Linda Burke then made some closing remarks on behalf of the aHUS alliance. Covering the scope of aHUS effects on patients and both clinical and social/economic impacts. She gave some thoughts on barriers to rare disease research but recognised how fortunate aHUS was that so many researchers are interested. She emphasised the range of organ involvement and the need for multi disciplinary approach.
She thanked all participants doctors , patients and pharma for their support.
That is it as Andrew Seidlecki closes the meeting.
A video record has been made and should be available by aHUS Awareness Day.
