Atypical hemolytic uremic syndrome (aHUS) is a rare disease in which abnormal activity of the complement cascade, a part of the immune system, causes blood clots to form in small blood vessels. These clots cause damage to internal organs, especially the kidneys.
aHUS is also a type of thrombotic microangiopathy (TMA), a group of diseases characterized by the formation of blood clots in the body’s small blood vessels, leading to organ damage.
Causes of aHUS
The complement cascade is a group of immunological proteins that, when activated, trigger a powerful inflammation and blood clotting reaction that can be useful for fighting disease-causing microbes. aHUS is caused by the abnormal activation of the complement cascade.
Most people with aHUS have genetic mutations that impair the body’s ability to regulate the complement cascade. However, mutations alone are not enough to cause aHUS. Usually, a disease trigger, such as an infection, is also needed.
More rarely, aHUS can be caused by self-reactive antibodies, and in some cases, there may not be a clear cause.
Symptoms of aHUS
aHUS has three cardinal symptoms: hemolytic anemia, thrombocytopenia, and acute kidney failure.
Hemolytic anemia occurs when red blood cells — those that transport oxygen in the bloodstream — are destroyed more quickly than they are produced, leading to insufficient oxygen delivery to the body’s tissues. Symptoms of anemia can include pale or yellow skin, fatigue, and a fast heart rate.
Thrombocytopenia refers to low levels of platelets, which are cell fragments that help blood to clot. Symptoms of thrombocytopenia can include easy bruising or abnormal bleeding.
Acute kidney failure occurs when the kidneys suddenly become unable to perform their normal function of filtering blood. Symptoms may include decreased urine output, swelling of the lower limbs, fatigue, nausea, and weakness.
Diagnosis of aHUS
People with aHUS commonly report feeling a general sense of illness, which is what initially prompts them to seek medical care. Like other types of TMAs, aHUS is characterized by laboratory findings indicative of hemolytic anemia, such as the presence of red blood cell fragments in a blood smear.
The major challenge of diagnosing aHUS is distinguishing it from other types of TMAs. This can be done with the help of certain laboratory tests, including one that measures the activity of an enzyme called ADAMTS13. aHUS can be further distinguished from typical HUS by testing for the presence of certain toxin-producing bacteria that normally cause this more common form of HUS.
Treating aHUS
Two medications are approved to treat aHUS in the U.S., EU, and other locations: Soliris (eculizumab) and Ultomiris (ravulizumab). Both have been developed and are being marketed by Alexion.
Soliris is an antibody-based therapy that works by binding to a specific component of the complement cascade, preventing the overactivation of the complement system. Ultomiris has a similar mechanism of action, but it has been modified so that it lasts longer in the body, allowing for less frequent dosing.
Because aHUS can cause kidney failure, treatment for the disease may also involve dialysis, in which the filtering functions normally performed by the kidneys are done by a specialized machine. For people with severe kidney failure, a kidney transplant may be necessary.
Last updated: April 29, 2021
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