With a bright new year already begun, February 2024 occurs as a rare ‘leap year’ with world Rare Disease Day held on the 29th. Traditionally, Rare Disease Day occurs each year on 28 February which is normally the last day of the month. It’s fortunate that there’s been no rarity of aHUS advancements, so we’re pleased to report many new additions to the ‘aHUS Virtual Library’ hosted by the aHUS Alliance Global Action team.
Accurate & Rapid aHUS Diagnosis is Vital, but Difficult
There are only a handful of aHUS patients per million, but some publications indicate that this rare disease may be under-reported. Among our additions are two recent publications that cover the essential topics of identifying and treating patients with atypical hemolytic uremic syndrome.
Informing Hematologists – Atypical HUS as part of TMA ‘MedEd’
At first glance those looking for atypical HUS topics might overlook a paper presented at this year’s ASH conference, held by the hematology community in December. Patients with active aHUS episodes usually have lab results that indicate low platelet numbers, as tiny clots form in small blood vessels to damage kidneys and other organs.
Titled Where have all the platelets gone? HIT, DIC, or something else? and authored by Rohith Jesudas and Clifford Takemoto, this aspect was presented as part of the December ASH2023 Education Program in the session ‘Alphabet Soup – Challenging Consults on the Pediatric Units’.
This was notable for several reasons:
a) Complement-mediated TMA (cm-TMA) is another term for atypical HUS, so its inclusion meant aHUS was part of the Education Program ASH 2023 offered to over 32,000 hematologists attending from 113 countries.
b) Atypical HUS is a diagnosis of exclusion, meaning that if other diseases with similar symptoms are ruled out, aHUS becomes the logical diagnosis apart from other syndromes of thrombotic microangiopathy (TMA).
c) On a personal note, readers of this article may be familiar with St Jude’s Children’s Research Hospital and its fine work which offers clinical care along with research efforts. Both authors list affiliation with St Jude Children’s Research Hospital in Memphis, Tennessee USA. It was heartening to imagine that perhaps charitable donations may have in some way supported a gain of awareness and information about diagnosing aHUS across the global hematology community.
Atypical HUS patient outcomes improve when rapid and accurate aHUS diagnosis leads toward obtaining appropriate treatment for the patient. That still remains a challenge, which is why we’re highlighting a new publication centered on the ‘TMA-INSIGHT score’ model with sequenced steps (or aHUS/TMA algorithms) to help clinicians sort through clinical characteristics and test data to classify types of TMA.
Steps to Diagnosis: Progress Made
Among the Brazilian team of authors led by Vanessa Vilani Addad, we see Lilian Monteiro Pereira Palma listed. Dr Palma has deep expertise in atypical HUS and is among the valued volunteers in our global network of aHUS clinicians and investigators. Developing an algorithm to distinguish aHUS apart from other TMAs is key to an early and accurate diagnosis so that appropriate treatment can be determined, thus providing the best chance for positive patient outcomes. Take a look:
Addad et al. A comprehensive model for assessing and classifying patients with thrombotic microangiopathy: the TMA-INSIGHT score. Thromb J. 2023 Nov 22;21(1):119. doi: 10.1186/s12959-023-00564-6. PMID: 37993892; PMCID: PMC10664252. (See more recent research on the topic of aHUS Diagnosis)
Special Topics: Pregnancy, Discontinuing Treatment, Multi-Organ Involvement
There were dozens of recent aHUS-specific research on a variety of topics, but since we can’t highlight them all here’s a brief selection from three categories.
Pregnancy – Yes, we’ve a whole list of publications specific to aHUS and which includes the range from pregnancy as a trigger for aHUS activity to postpartum issues. While we’ve just added six more publications to our Pregnancy scroll, here’s one just published on 29 Jan 2024 which we’d like to call to your attention:
While other publications focus on medical aspects of aHUS and pregnancy, this is a rare example of clinicians taking a holistic approach which focused on the social-emotional aspects involved. Indeed, it directly addressed one of 15 key points within the Global aHUS Patients’ Research agenda (Item 5.2). People with a known genetic predisposition for atypical HUS worry about whether their children will inherit a similar genetic missense. Women with past aHUS activity ponder risk factors not only for their future family members, but also about their own maternal health risks given that pre-existing medical issues may translate into their classification as a ‘high risk pregnancy’. But this is one of the first times we’ve seen this complex topic addressed with such sensitive and insightful commentary, to include this statement:
“We, as nephrologists, can only classify her possible future pregnancy as being at extremely high risk. However, no numbers are available, and no number will likely make a difference to a woman who desperately wants a baby. There is no absolute threshold for a “too high risk”, as for some women a 10% risk may be not acceptable, while for others a 10% chance would be enough to try.”
Younis D and Shemies RS. The unanswered question. When to undertake a maternity journey? J Nephrol. 2024 Jan 29. doi: 10.1007/s40620-023-01865-9. Epub ahead of print. PMID: 38285317.
Discontinuing Treatment – Among the recent publications related to stopping treatment and gauging risks, we’d like to highlight this one:
Spasiano et al. Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation? Int J Mol Sci. 2023 Sep 24;24(19):14496. doi: 10.3390/ijms241914496. PMID: 37833944; PMCID: PMC10572301.
Notice that it was published in the International Journal of Molecular Science, which rather begs the question, “How many nephrologists and hematologists have seen this?” That underscores something familiar with aHUS families and advocates; it’s important for us to be vigilant and to feel comfortable to bring such publications to the attention of our medical team members.
If aHUS genetics can help to identify disease management and risk aspects, to include prediction of potential for relapse off treatment, that’s something of vital interest to patients and their families. So much in fact, it was address with item #1 on the Global aHUS Patients’ Research Agenda (click for pdf version). Check out the scrolling list within our ‘virtual library’ of aHUS-specific research on the topic of Discontinuing Treatment/Relapse. (Note: This particular piece is cross-referenced under the category Genetics for obvious reasons.)
Multi-Organ Involvement – The aHUS Alliance Global Action team is a group of volunteers who strive to connect, inform, and collaborate with an end goal of promoting better aHUS patient outcomes. We care because, as patients or family caregivers ourselves, we’re directly affected by the impact of atypical HUS on all areas of our lives.
When aHUS activity ramps up and forms tiny clots in the body’s small blood vessels, it affects normal body function. Any human body location with blood flow can experience this clot blockage disruption, with damage to functioning which varies and may include aHUS activity as a cause of organ failure.
Atypical HUS used to be considered a kidney disease, but that’s fading with publications which note aHUS impact on various organs and systems. Recent papers in our scrolling list on the topic Extra-Renal: Effects on the Body involve damage related to the heart, eyes, and brain. That’s why aHUS patients and their families need a multi-disciplinary approach to care, so our medical team members can collaborate on complex care that can affect multiple organs.
Eyes
Garrell-Salat et al. Journal Français d’Ophtalmologie, Vol 47, Issue 1, 2024 Ophthalmic manifestations in atypical hemolytic uremic syndrome triggered by intravitreal anti-VEGF
Heart
Kavgacı et al. Clinical Pediatrics. 2024;0(0) Cardiac Manifestation in a Child With Atypical Hemolytic Uremic Syndrome
Brain
Neuman et al. J Neurol. 2023 Oct; 270(10):5023-5033. Predictors of acute ischemic cerebral lesions in iTTP and hemolytic uremic syndrome
Brain
Kunwar et al. Clin Case Rep. 2024 Jan; 12(1): e8356. Atypical hemolytic uremic syndrome in a child: A rare case report
Since aHUS can affect multiple organs, one would assume that the majority of patients would regularly receive care from a multidisciplinary team. Sensible assumption, since that would save time and expense for the healthcare community, as well providing likelihood of better patient outcomes. Atypical HUS surveys about patient experiences indicate that this is not the reality. Hence the publication below, with Linda Burke providing the aHUS caregiver voice. We’re honored that this esteemed team of clinicians and researchers from nations around the world (USA, Canada, India, France, and So Africa) lent their expertise and efforts to highlight the need for aHUS multidisciplinary care teams.
Collaborative Care for aHUS Patients – making the Case (Multiple Organ involvement, for aHUS patients regardless of age.) Burke L, Sethi SK, Boyer O, Licht C, McCulloch M, Shah R, Luyckx VA, Raina R. Voice of a caregiver: call for action for multidisciplinary teams in the care for children with atypical hemolytic uremic syndrome. Pediatr Nephrol. 2023 Oct 2
The aHUS Alliance Global Action team remains strong advocates for those affected by aHUS, and proudly partners with people and groups dedicated to shedding light on clinical care, filling in knowledge gaps, and working together to build a brighter future for those affected by this rare disease.
A ‘Virtual Library’ of aHUS-specific Research – What is that?
Often publications with advancements and insights into this very rare disease are scattered across medical journals related to nephrology and hematology specialties, but atypical HUS information can be found under varied terms and across specialty areas. That’s where we come in, since as aHUS patients and family caregivers ourselves we have a vested interest in staying up-to-date with current research. It’s likely that other families affected by aHUS may wish to key into a specific topic, so to aid navigation of our ‘Research and Publications’ page we’ve not only categorized entries but also have added links to jump to each Scroll (topic section) to speed your search.
Research articles about atypical HUS are listed within our website on topic-specific lists within our Info Centre, where you can see a list for “New Research” which are then also listed by category. Scroll topic categories are: New Research, Critical Care, Diagnosis, Treatment, Discontinuing Treatment/Relapse, Thrombotic Microangiopathy (TMA), Extra Renal (Effects on Organs other than Kidneys), Pregnancy, Transplants, Genetics, Complement, Secondary aHUS, Triggers, Research in Specific Nations, Case Studies, Patient Registries: Publications, Drug Discovery/Research, Summary Articles/Literature Reviews, Consensus Documents/Guidelines, and Varied Topics.
(Note: All entries from the ‘New Research’ scroll additionally are cross-listed at the start of each specific topic. While this ‘library’ has grown to more than 1,300 unique publications, it results in about 1700 with dual entries – such as a study that examines mutation impact on disease management, and thus listed on both Genetics and Treatment scrolls.)
Visit our ‘virtual library’ of over 1,300 publications specific to aHUS
by clicking this link: Atypical HUS Research & Publications
