Atypical hemolytic uremic syndrome (aHUS) is a rare disorder that causes blood clots to form in the body’s small blood vessels. This causes damage to several internal organs, especially the kidneys.
aHUS also is a type of thrombotic microangiopathy (TMA), which comprises a group of disorders characterized by the formation of blood clots in the body’s small blood vessels. A major challenge in diagnosing aHUS is differentiating it from other types of TMA.
What is TMA, and how is it diagnosed?
TMAs are characterized by the combination of hemolytic anemia (red blood cells’ destruction), thrombocytopenia (low platelet counts), and organ damage due to the formation of blood clots in small blood vessels. There are two main forms of TMA: hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). HUS can be subdivided further into typical HUS and aHUS.
A main feature used to diagnose TMAs is evidence of hemolytic anemia in laboratory testing, most notably the presence of schistocytes (pieces of destroyed red blood cells) on a peripheral blood smear.
Low levels of hemoglobin (the protein red blood cells use to carry oxygen), haptoglobin (a protein that helps regulate hemoglobin levels), and platelets can be identified by laboratory testing and aid in the diagnosis of TMAs. High levels of an enzyme called lactate dehydrogenase also are indicative of hemolytic anemia and are characteristic of TMAs.
In order for a TMA to be diagnosed, these laboratory changes must be accompanied by clear evidence of organ dysfunction. While any organ can be affected by a TMA, the most commonly affected are the kidneys, as they contain a high number of small blood vessels. The nervous system and digestive tract also are commonly affected by TMAs.
Distinguishing TTP from HUS
A test commonly used to distinguish between TTP and HUS is measuring the activity of an enzyme called ADAMTS13. TTP is characterized by near-absent ADAMTS13 activity, whereas people with HUS usually have normal or slightly reduced activity of this enzyme.
Differences between typical HUS and aHUS
Typical HUS and aHUS have very similar symptoms, but they have different biological causes. Typical HUS is caused by an infection of E. coli bacteria that produce a toxic protein called Shiga toxin. Typical HUS accounts for more than 90% of HUS cases. By contrast, aHUS is not caused by a bacterial infection, but by the abnormal activation of part of the immune system, called the complement cascade.
As such, differentiating between typical HUS and aHUS generally involves a first step of testing for the presence of Shiga-producing E. coli. A positive test result usually suggests the presence of typical HUS, while a negative result can be indicative of aHUS.
aHUS can be further differentiated from typical HUS by tests that measure the activity of certain components of the complement cascade, though such testing often requires specialized laboratories. Genetic testing also can identify mutations in complement-regulating genes that can predispose a person toward developing aHUS, thereby helping physicians reach a diagnosis.
Differences in the symptoms that are experienced commonly by people with typical HUS or aHUS also may aid healthcare providers in making an accurate diagnosis. For example, people with typical aHUS frequently have bloody diarrhea, whereas those with aHUS usually do not experience that. However, because there can be a substantial overlap in symptoms, medical testing is typically required to differentiate the two conditions.
Last updated: April 27, 2021
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