Answer 80 = [B] Factor H
Answer 81 = [B] Eculizumab
Atypical HUS
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure.
Hemolytic uremic syndrome (HUS) is one of the disease processes that belong to thrombotic microangiopathies (TMAs)
CLASSIFICATION
[1] Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with STEC
[2] aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation.
Note = Among the 30% to 50% of patients with aHUS who have no detectable complement defect, some have either impaired diacylglycerol kinase ε (DGKε) activity, cobalamin C deficiency, or plasminogen deficiency.
In aHUS, mutations have been reported in 5 central complement proteins [Factor H, MCP (CD46), Factor I, C3, Factor B]. Most of these mutations lead to impaired regulation of alternative pathway activation. Most commonly involved gene is of Factor H (25-30% of cases)
TREATMENT OPTIONS
Historically, aHUS had a poor prognosis with about 50% of all patients progressing to end-stage renal disease (ESRD).
Prior to the introduction of eculizumab, plasma infusion or plasma exchange (PI/PE) was the standard of care by supplying the normal/functional complement inhibitory molecules, but they do not address the underlying pathology.
Eculizumab, a terminal complement inhibitor that binds to C5 with high affinity, blocks the generation of proinflammatory C5a and C5b-9. Approved in 2011 in the United States, it is the drug of choice for the treatment of aHUS; immediate treatment with eculizumab is strongly recommended when the diagnosis of aHUS is confirmed.