Diagnosis of aHUS

Patients with aHUS are at ongoing risk of systemic, life-threatening, and sudden complications1-3,6


Severe ADAMTS13 deficiency (TTP)

The underlying cause in TTP is a severe deficiency in ADAMTS13 activity (≤5%)47-50

Insufficient ADAMTS13 activity (≤5%) leaves von Willebrand (vWF) factor uncleaved, causing excessive platelet aggregation47, 50, 55, 56

Genetic, complement-mediated TMA (aHUS)

aHUS is caused by chronic, uncontrolled complement activation5, 14, 15, 26, 27, 53-55

Genetic defects in activators and/or inhibitors lead to chronic activation of the complement system, causing endothelial cell damage and continuous platelet aggregation5, 14, 15, 26, 27, 53-55

Serum creatinine levels (SCr) and platelet count can be used to predict ADAMTS13 activity in patients with TMA57,66-70

A patient with a TMA presenting with SCr >1.7 mg/dL OR platelet count >30,000/mm3 is 21.8 times less likely to have severe ADAMTS13 deficiency (TTP) than those who meet neither criteria

  • In a national registry of 214 TMA patients, baseline SCr and platelet count were identified as independently predictive values of ADAMTS13 deficiency*66.
  • Multiple studies on a total of 806 patients with TMA have demonstrated that baseline values of SCr and platelets at clinical presentation can rapidly and efficiently distinguish between sufficient and severely deficient ADAMTS13 activity57,66-70

Though not required for diagnosis, the following may help determine if aHUS is the underlying cause of TMA:

  • Patient's medical history includes previous TMA3,19
  • Patient reports family history of renal impairment6,19,40

Complement-amplifying conditions place patients with aHUS at high risk for TMA manifestations4,21,26,41

  • TMA is very rare among the general population42-44
  • A patient who presents with TMA and an identifiable complement-amplifying condition may have a defect in complement regulation4,21,26,41

aHUS has been unmasked in a percentage of patients experiencing TMA in the presence of a complement-amplifying condition5

69% of patients with aHUS showed their first clinical manifestation while experiencing one of the following complement-amplifying conditions (N=191)5

31% 20% 49%
*Eg, systemic lupus erythematosus and scleroderma.
Complement amplification occurs frequently and is not always apparent14,17,20,21
  • Complement-amplifying conditions include and are not limited to14,17,20,21
    • Bacterial, viral, and fungal infections
    • Atherosclerosis
    • Inflammatory bowel disease
    • Surgeries
    • Thyroiditis
    • Allergies
    • Asthma
    • Anaphylactic Shock

A clinical diagnosis of aHUS should be considered in patients presenting with both a complement-amplifying condition and TMA24,41,45

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