Their study, “Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome,” was published in The Korean Journal of Internal Medicine.
Thrombotic microangiopathy, or TMA, is a medical condition in which the small blood vessels found inside some organs in the body, particularly the kidneys, become clogged, potentially leading to other complications, such as kidney failure.
TMA can be triggered by several medical conditions, including infections, pregnancy, cancers, autoimmune diseases, as well as by the use of certain medications.
aHUS, a rare genetic disorder caused by the progressive destruction of red blood cells due to dysregulation of the complement system, can also be associated with TMA. Of note, the complement system comprises a set of more than 20 blood proteins that form part of the body’s immune defenses.
“These overlapping manifestations hamper differential diagnosis of the underlying [causes of TMA], despite recent advances in understanding the mechanisms of several types of TMA syndrome,” the researchers wrote.
For the study, a group of South Korean experts, including hematologists, nephrologists (kidney specialists), and transplant surgeons, gathered to establish a set of new diagnostic criteria that would enable physicians to distinguish the different medical conditions leading up to TMA, with a particular emphasis on aHUS.
“Differentiating among TMA syndromes is difficult but crucial because of the need for distinct therapeutic approaches,” the experts wrote.
They recommended that patients showing signs of TMA and organ injury should first be tested for the presence of Shiga toxin-producing E. coli (STEC) or Shigella — strains of bacteria that can cause infections leading up to typical hemolytic uremic syndrome (HUS) and TMA.
In addition, the activity of von Willebrand factor-cleaving protein, also known as ADAMTS13, should also be assessed in these patients to discard thrombotic thrombocytopenic purpura (TTP), a condition in which small blood vessels throughout the body become leaky, causing bleeding and extensive bruising.
According to the experts, all patients with normal ADAMTS13 activity (greater than 10%) and showing no signs of STEC should be suspected of having TMA associated with aHUS. They also stated that children showing signs of TMA without gastrointestinal infections should be immediately assumed to have aHUS and promptly treated, since TTP is uncommon in this age group.
The physicians also stressed the importance of considering aHUS in the differential diagnosis of all patients showing signs of TMA in the presence of other known TMA triggers, including infections, pregnancy, autoimmune diseases, and cancer, due to the incomplete genetic penetrance of the disease.
Genetic penetrance evaluates the proportion of individuals who develop a disorder as a result of carrying a particular genetic mutation. Complete penetrance indicates that all individuals carrying a particular mutation will develop the disease, while incomplete penetrance indicates that only a fraction of individuals carrying the same mutation will develop the disease.
In disorders such as aHUS with incomplete genetic penetrance, other factors often influence the onset of the disease.
The experts also emphasized that the complement inhibitor eculizumab (sold as Soliris by Alexion) should be the first-line treatment for adults and children with aHUS. In the cases where eculizumab is unavailable, plasma exchange and/or infusion should be considered as options.
“The diagnosis of aHUS is complex and challenging, but is essential because of the devastating consequences of inadequate treatment. Advances in our understanding of the clinical, molecular, and functional aspects of the pathogenesis of aHUS are ongoing and have resulted in the development of novel therapeutic options,” the experts wrote.
“Several areas require further investigation, including factors that trigger aHUS and the optimal duration of treatment. Clinicians may refer to this current consensus for insights regarding diagnosis and treatment strategies for patients with aHUS,” they added.
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