Understanding atypical-HUS aids in rapid diagnosis and disease management

Review key details about atypical-HUS to help your patients manage this systemic, life-threatening disease.

What is atypical-HUS?

Atypical hemolytic uremic syndrome (atypical-HUS) is a rare, chronic disease that can onset at any age. It has an annual incidence* of about 0.35 to 2 per million people.1,5,32,33 Atypical-HUS is caused by dysregulation of the alternative pathway in the complement system, leading to thrombotic microangiopathy (TMA) and progressive organ damage.6,7 Patients with atypical-HUS can be at continuous risk of the life-threatening consequences of unpredictable complement-mediated TMA.5

Atypical-HUS manifests with:

  • Clinical characteristics of TMA4
    • Thrombocytopenia
    • Microangiopathic hemolysis
    • Symptoms of organ dysfunction
  • Absence of other underlying causes of TMA4†
    • ADAMTS13 activity >5% (ruling out thrombotic thrombocytopenia purpura [TTP])
    • Negative Shiga toxin-producing E. coli (STEC) test (ruling out STEC-HUS)

Learn more about how uncontrolled complement activity leads to an ongoing risk of TMA in atypical-HUS.1

*Incidence refers to the occurrence of new cases of atypical-HUS in a population over a 1-year period.31

†Where TTP and STEC-HUS have been ruled out, the TMA can be attributed to complement dysregulation. Atypical-HUS is a complement mediated TMA (CM-TMA) that has been more broadly or narrowly defined in different contexts, based on such factors as the presence and nature of a trigger and/or identification of an underlying genetic mutation.4,12,28

COMPLEMENT SYSTEM & aHUS

Approximately 50% of adult patients with atypical-HUS are at risk for end-stage renal disease (ESRD) and death7‡

Chronic, uncontrolled complement activity in atypical-HUS leads to ongoing endothelial injury, organ damage, and sudden death.5,8 Familiarize yourself with the clinical complications of atypical-HUS to rapidly recognize the signs of damage in multiple organ systems and prevent further progression in your patients.

‡5-year ESRD-free survival7

CLINICAL COMPLICATIONS
Pregnancy/Postpartum
Malignant Hypertension
Organ Transplantation
Autoimmune Diseases
Glomerulonephritis
Malignancy
Infections
CertainMedications
Surgery/Trauma

These are some triggers seen in atypical-HUS patients. Additional triggers may exist.

70% of patients (191/273) with atypical-HUS presented their first clinical manifestation while experiencing a trigger3

Triggers can amplify complement system activation and unmask underlying atypical-HUS. Some of these triggers include pregnancy or postpartum experiences, autoimmune disease, malignant hypertension, and organ transplantation.1,2 Understanding how patients may present with triggers can help to appropriately diagnose atypical-HUS.4

aHUS TRIGGERS & DIAGNOSIS

Diagnosing atypical-HUS requires ruling out other causes of TMA

TMAs associated with triggers1

Alternate Text Alternate Text

NOTE: The diagram is for illustrative purposes only; disease areas are not drawn to proportional scale and are not meant to reflect relative incidence.

Adapted from Azoulay E, et al. Chest. 2017;152(2):424-434.

Plasma therapy is the initial standard of care for undifferentiated TMA. However, there are limitations to plasma exchange/plasma infusion (PE/PI) in atypical-HUS. Patients remain at risk of impaired renal function and death, regardless of hematologic improvement after PE/PI. Differentiating your patients’ diagnosis between atypical-HUS or TTP is critical for rapid and appropriate disease management.4

DIAGNOSING aHUS