Differential Diagnosis

Distinguishing typical HUS from atypical HUS (aHUS). Typical HUS is triggered by infective agents such as certain strains of Escherichia coli that produce the Shiga-like powerful exotoxins (Stx-E coli). Typical HUS triggered by Stx-E coli manifests as an acute disease with a prodrome of diarrhea (D+HUS), often bloody. However, approximately 25% of typical HUS is diarrhea negative. During an acute episode, identification of Shiga toxins in the stools (by the Vero cell assay) and/or serum antibodies against Shiga toxin (by enzyme-linked immunosorbent assay [ELISA]) and/or lipopolysaccharides (LPS) (O157, O26, O103, O111, and O145, by ELISA) distinguishes typical HUS (D+HUS or D–Stx+HUS) from aHUS (D–Stx–HUS).

Source: GeneReviews — "Genetic Atypical Hemolytic-Uremic Syndrome"

Clinical Guidance

Discontinue cyclosporine or tacrolimus when aHUS develops following challenge with the medication. Fresh frozen plasma should be avoided (i.e., plasma therapy is contraindicated) in persons with aHUS induced by Streptococcus pneumoniae because plasma from an adult contains antibodies against the Thomsen-Friedenreich antigen, which may exacerbate the disease. It is preferable to transfuse washed red blood cells or platelets. There is no evidence that plasmapheresis is of value . Avoid potential precipitants of aHUS, including the following known triggers:

• Pregnancy

• Medications: some chemotherapeutic agents (e.g., mitomycin, cisplatin, daunorubicin, bleomycin, cytosine arabinoside, gemcitabine), immunotherapeutic agents (e.g., cyclosporin, tacrolimus, muromonab-CD3, interferon, quinidine), antiplatelet agents (e.g., ticlopidine, clopidogrel), oral contraceptives, and anti-inflammatory agents

Source: GeneReviews — "Genetic Atypical Hemolytic-Uremic Syndrome"

Therapies Under Investigation

A clinical trial is currently evaluating the efficacy and safety of crovalimab in adult and adolescent participants with aHUS. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Genetic Atypical Hemolytic-Uremic Syndrome"