Article No. 376
10 September 2020
It is not unheard of for someone with atypical Haemolytic Uremic Syndrome (aHUS) to have had an initial diagnosis of Thrombotic Thrombocytopenia Purpura (TTP). There is no statistic for how many have been misdiagnosed, just anecdotal evidence popping up over the years. Such misdiagnosis is often discovered when a patient receiving a kidney transplant presents with another episode of aHUS triggered by the transplant. It may only be then that genetic tests reveal that the patient was indeed predisposed to aHUS.
Both diseases share the damaging process of Thrombotic Microangiopathy, TMA, and are remarkably similar in initial presentation. Similarly, they are triggered by pregnancy. Both are referred to as Primary TMAs (1). Something they share too with HUS, which is the typical version of aHUS, if that makes sense. HUS is specifically the TMA triggered by an E. coli infection. aHUS began to be seen as sitting between TTP and HUS with overlaps with them.
At one time of course there was only TTP, which is what the “clumping disorder” described by Moschowitz (2) became known as in the 1920s. The term TMA to describe something which was not TTP did not arrive until 1951 when Symmers coined the phrase in a BMJ article (3). In 1955 Haemolytic Uraemic Syndromes first appeared as a diagnosis by Swiss doctor Conrad von Gasser (4) for both typical and atypical versions. The atypical HUS nomenclature did not appear until 1990s. Even then it was commonplace to refer to our diseases as TTP/HUS or HUS/TTP, being two entities within an entity.
In time, TTP became linked with a deficiency of ADAMTS13 and its ability to cleave Von Willebrand factor, whether acquired or genetic in cause (5). aHUS became linked with genetic defects in the innate immune system which led to an unregulated and damaging over activation of Complement (6). aHUS was further subdivided so that a Secondary version of aHUS was created to confuse matters even further for aHUS patients.
Whilst the increasing differentiation of our diseases was becoming complex enough, along came a proposal for re-classification of all TMAs as exemplified by the model published by TMA Group in Vienna Austria (7). The Vienna Group are not alone in thinking this way and gradually new disease descriptions are being used to replace the traditional TTP, HUS, and aHUS. All based on what type of TMA they are but recognising overlaps both within and with other classifications.
HUS becomes an Infection TMA caused by E. coli. aHUS becomes a complement mediated TMA or cTMA. TTP becomes an ADAMTS13 Auto TMA or ADAMTS13 Variant TMA depending on whether it is the acquired or inherited version.
Whatever the outcome of the debate about TMA classification it will be important for all that TMA awareness is increased. Those patients “blue lighted” into UCL with suspected TMA will not know at that moment the pathway they will eventually follow.
For aHUS patients quick diagnosis is about exclusion of the other Primary TMAs as there is no specific blood test that identifies aHUS. So quicker recognition of a TMA leads to quicker identification of what will be TTP through speedier ADAMTS13 tests. The sooner that a TTP TMA is ruled out, the sooner aHUS/cTMA is thought about, and if no E. coli Infection TMA can be found, aHUS/c TMA can be diagnosed. Then an effective complement inhibitor treatment can commence.
The 24th September is International aHUS Awareness Day (8). But it is also important that awareness of all TMAs is raised, particularly TTP, and that our specific diagnoses are made sooner for all.
The sooner the diagnosis , the sooner the treatment. The sooner the treatment, the better the outcome. The better the outcome , the quicker wellness and well being returns.
Our similarities can help with our differences.
Just 2 weeks to aHUS Awareness Day 2020 on September 24th.