Hemolytic Uremic Syndrome

Establish thrombotic microangiopathy (TMA) with a complete blood count, peripheral smear for schistocytes, creatinine, urinalysis, reticulocyte count, and hemolysis testing including haptoglobin. HUS is classically defined by nonimmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury; schistocytes are a critical diagnostic smear finding. BMJ+2BMJHemolytic uremic syndrome - Symptoms, diagnosis and treatment | BMJ Best Practice USScienceDirectHaemolytic uraemic syndromecdn clinicaltrialsProtocol Amendment 2 Anonymized

Quantify kidney involvement at presentation with creatinine trend, urine output, urinalysis, and protein measurement when urine is available. Hematuria, hemoglobinuria, and substantial proteinuria can accompany complement-mediated HUS; persistent proteinuria despite hematologic improvement should prompt assessment for renal TMA or an alternative glomerular process. Wolters KluwerWolters KluwerComplement-Mediated Hemolytic Uremic Syndrome... : Journal of the American Society of Nephrology

Assess neurologic symptoms, blood pressure, volume status, gastrointestinal symptoms, and evidence of systemic infection while drawing the discriminating tests. Confusion or seizures and severe hypertension increase urgency for monitored care and parallel hematology-nephrology management; HUS may present with decreased urine output, hematuria, bloody diarrhea, edema, and neurologic symptoms. cdn clinicaltrialscdn clinicaltrialsProtocol Amendment 2 Anonymized

Test for Shiga toxin-producing organisms in any compatible diarrheal or foodborne illness, but do not restrict testing to children: STEC-associated HUS also occurs in adults. In a CDC adult cohort, diagnosis required thrombocytopenia below 150,000 cells/µL, hemoglobin below 12 g/dL, AKI, and PCR detection of stx1, stx2, or both. CDC+1CDCShiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, ...CDCShiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017 - Volume 27, Number 7—July 2021 - Emerging Infectious Diseases journal - CDC

Do not use C3, C4, CH50, factor H, factor I, or CD46 abnormalities alone to diagnose complement-mediated HUS in the acute setting. Among adults with STEC-HUS, low CH50 occurred in 38.8% and low CD46 in 65.7%, and the investigators noted that acute kidney injury and inflammation can confound complement measurements. CDC+1CDCShiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, ...CDCShiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017 - Volume 27, Number 7—July 2021 - Emerging Infectious Diseases journal - CDC

Prioritize exclusion of TTP because it changes acute treatment. In a clinical diagnostic approach to atypical HUS, TTP and Shiga toxin HUS should be excluded within approximately 48 hours before eculizumab is started; severe ADAMTS13 deficiency should redirect the diagnosis toward TTP. Oxford Academic+1Oxford AcademicAtypical hemolytic uremic syndrome - Oxford AcademicWolters KluwerDoes Severe ADAMTS13 Deficiency in Thrombotic... : Saudi Journal of Kidney Diseases and Transplantation

If Shiga toxin testing is negative and ADAMTS13 is not severely deficient, search systematically for secondary TMA before diagnosing primary complement-mediated HUS. Relevant associations include medications, cancer, systemic disease, hematopoietic stem-cell transplantation, invasive pneumococcal infection, Haemophilus influenzae infection, and cobalamin C defect. BMJ+3BMJHemolytic uremic syndrome - Symptoms, diagnosis and treatment | BMJ Best Practice USWolters KluwerDoes Severe ADAMTS13 Deficiency in Thrombotic... : Saudi Journal of Kidney Diseases and Transplantationpublications aapHemolytic Uremic Syndrome | Pediatric Care Onlinecdn clinicaltrialsTITLE PAGE

For confirmed STEC-HUS, provide supportive management directed at AKI, volume status, hypertension, electrolyte abnormalities, and neurologic complications; supportive care remains the backbone of therapy. STEC-associated HUS accounts for approximately 90% of pediatric HUS cases. ScienceDirect+1ScienceDirectHemolytic Uremic Syndrome - ScienceDirectpublications aapAn Overview of Pediatric Hemolytic Uremic Syndrome

Do not diagnose complement-mediated HUS solely because complement studies are abnormal during STEC-HUS. Acute complement findings may reflect kidney injury or inflammation, and routine complement-gene screening is not generally performed in pediatric STEC-HUS. CDC+1CDCShiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, ...CDCShiga Toxin–Associated Hemolytic Uremic Syndrome in Adults, France, 2009–2017 - Volume 27, Number 7—July 2021 - Emerging Infectious Diseases journal - CDC

Eculizumab has been used in severe STEC-HUS, including during the 2011 German outbreak, but the cited outbreak analysis describes its widespread use rather than establishing routine benefit. A 2024 literature review identified 80 eculizumab-treated STEC-HUS cases, with complete neurologic symptom resolution reported in 68.7%; this uncontrolled evidence should not substitute for confirmation of complement-mediated disease. BMJ+1BMJValidation of treatment strategies for enterohaemorrhagic ...WileyEculizumab for Shiga‐toxin‐induced hemolytic uremic ...

Complement-mediated HUS, historically termed atypical HUS, is driven by overactivation of the alternative complement pathway. Genetic abnormalities can involve complement regulatory proteins or complement activators, while acquired disease can involve anti-factor H antibodies. BMJ+2BMJHemolytic uremic syndrome - Symptoms, diagnosis and treatment | BMJ Best Practice USWileyComplement‐driven hemolytic uremic syndromeScienceDirectHemolytic Uremic Syndrome - an overview | ScienceDirect Topics

Once TTP and Shiga toxin HUS have been excluded, eculizumab is the principal complement-directed treatment described for complement-mediated HUS. A clinical review recommends beginning eculizumab after those exclusions, which should be achievable within 48 hours; anti-complement therapy has transformed outcomes in this disease category. Oxford Academic+1Oxford AcademicAtypical hemolytic uremic syndrome - Oxford AcademicScienceDirectHaemolytic uraemic syndrome

The outbreak schedule of eculizumab reported for severe Shiga toxin-associated HUS was 900 mg on days 0, 7, 14, and 21, followed by 1,200 mg thereafter; this regimen was reported in an outbreak context and should not be extrapolated as a general dosing recommendation for all HUS phenotypes. BMJBMJValidation of treatment strategies for enterohaemorrhagic ...

If anti-factor H antibodies are identified, the disease mechanism is acquired complement dysregulation rather than solely inherited complement dysfunction. Reports cited in the literature describe improved outcomes with prompt plasma exchange and immunosuppression in pediatric anti-factor H antibody-associated HUS, supporting early recognition of this subgroup. ScienceDirect+1ScienceDirectPathophysiology and treatment of typical and atypical hemolytic uremic syndrome - ScienceDirectScienceDirectHemolytic Uremic Syndrome - an overview | ScienceDirect Topics

Secondary HUS/TMA may occur with medications, malignancy, systemic diseases, transplantation, and invasive bacterial infections. A trigger should not be treated as incidental: define whether the timing and phenotype support a causal role, discontinue a plausible offending medication when feasible, and treat the associated disease while completing TTP and Shiga toxin exclusion. BMJ+3BMJHemolytic uremic syndrome - Symptoms, diagnosis and treatment | BMJ Best Practice USWolters KluwerDoes Severe ADAMTS13 Deficiency in Thrombotic... : Saudi Journal of Kidney Diseases and Transplantationpublications aapHemolytic Uremic Syndrome | Pediatric Care Onlinecdn clinicaltrialsTITLE PAGE

In patients receiving immune checkpoint inhibitors, a protocol-based HUS workup includes CBC, blood smear morphology, creatinine, ADAMTS13, homocysteine, methylmalonic acid, C3, C4, CH50, and complement inhibitory antibodies when familial disease is suspected. The same protocol advises hematology involvement and plasma exchange according to existing guidance for severe immune-mediated hematologic toxicity. cdn clinicaltrialscdn clinicaltrialsProtocol Amendment 2 Anonymized

Engage nephrology and hematology early when AKI, marked thrombocytopenia, neurologic findings, uncertain TMA subtype, or suspected complement-mediated HUS is present. The key operational goal is not merely to name HUS, but to exclude ADAMTS13-deficient TTP and STEC-HUS quickly enough that complement-directed therapy is not delayed when indicated. Oxford Academic+2Oxford AcademicAtypical hemolytic uremic syndrome - Oxford AcademicWolters KluwerDoes Severe ADAMTS13 Deficiency in Thrombotic... : Saudi Journal of Kidney Diseases and TransplantationScienceDirectHaemolytic uraemic syndrome