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Resources to support your practice at every step of the clinical pathway

Below, you'll find pathways and practice recommendations to help establish a consistent, coordinated approach to aHUS diagnosis, referral, and management across Canada.

Quick Links :
aHUS testing centres

Select a step in the clinical pathway to view related resources

  • TMA is a medical emergency. Early identification, differential diagnosis, and appropriate intervention can significantly improve patient outcomes and reduce end-organ damage.

    (Refer to McFarlane et al., 2021) 1
    1 Initial assessment
    Confirm TMA

    Including C3 & C4 levels

    Evaluate end organ damage
    Treat hypertension

    Active BP management

    2 Differential diagnosis

    Certain samples must be drawn prior to plasma exchange

    RULE OUT
    Primary TMAs
    TTP
    Thrombotic thrombocytopenic purpura
    Infection-associated TMA
    HUS
    Hemolytic uremic syndrome (STEC/EHEC-associated)
    TMAs with coexisting conditions
    Pregnancy-related MAHA
    Microangiopathic hemolytic anemia
    TA-TMA
    Transplant-associated TMA
    DIC
    Disseminated intravascular coagulation
    Malignant hypertension
    Systemic rheumatic diseases
    Including CAPS (catastrophic antiphospholipid syndrome)
    Malignancy-associated TMA
    3 If the TMA fails to improve within 48–96h, and:
    • ADAMTS13 score is normal and/or PLASMIC score is low
    • STEC/EHEC is negative or not clinically indicated
    IN PARALLEL
    A Make clinical diagnosis

    Start C5i therapy

    Treatment should not be delayed while awaiting results from Core aHUS Panel or genetic testing
    B Document patient baseline
    • Order:
      • Core aHUS Panel (see description in section below)
      • Complement genetic panel
    Both panels will support ongoing patient monitoring and management decisions

  • This proposed "Core" aHUS panel aims to provide national standardization of baseline metrics for suspected aHUS cases. The markers included in the panel emphasize the complement Alternative Pathway. Results are not required prior to starting C5i therapy.

    The panel includes:

    1
    CH50/C100 & AH50 (AP50) (likely to be a repeat test)
    2
    Soluble plasma C5b9
    3
    Autoantibodies for Complement Factor H (Anti-CFH)

    When to order the Core Panel

    1

    At the time of diagnosis (baseline)

    Treatment should not be delayed while awaiting results.

    2

    As part of a pre-transplant workup

  • Access to specialized laboratory testing is essential for the accurate diagnosis of aHUS. The following information outlines available tests by category and which sites provide them across Canada.

    Outside of Canada, options for complement genetic testing include BluePrint Genetics and Fulgent Genetics.

    Labs at the University of Iowa and Cincinnati Children's Hospital also offer complement testing.

    Complement genetic testing in Canada
    Centre d'Expertise at CHU Sainte Justine

    Montreal, QC

    View requisition form

    To come / à venir

    London Health Sciences Centre (LHSC)

    London, ON

    View requisition form

    Select STAT testing option to obtain results in 2–4 weeks. Regular turnaround time is 2–3 months.

    IWK Health

    Halifax, NS

    View requisition form

    Testing Menu: IWK CGL Test Menu

    Blood-based testing in Canada

    Click on a site name to go to online information about requisitions.

    Serum (red-top tube) EDTA (lavender-top tube)
    Test Centre d'Expertise at CHU Sainte Justine MitogenDx MUHC CHUQ Notes
    Autoantibody
    CFH Complement Factor H sent to CHUQ
    CFI Complement Factor I
    Anti-CFH Autoantibodies against Complement Factor H or
    Complement Function
    CT (CH50/CH100) Total Hemolytic Complement Activity Classical pathway
    NB. CH50 values may be inconsistent with expected therapeutic concentrations of ravulizumab.2,3
    AH50 (AP50) Alternative Pathway Hemolytic Activity Alternative pathway
    Plasma sC5b9 Soluble Membrane Attack Complex or Terminal activation marker
    Endothelial Marker
    Endothelial deposition sC5b9 In development Validation samples needed
    Therapeutic Monitoring
    Eculizumab level Anti-C5 monoclonal antibody Terminal complement inhibitor
    Ravulizumab level Long-acting anti-C5 monoclonal antibody In development Terminal complement inhibitor

    Specimen handling note

    Please refer to each laboratory's specific requirements for specimen collection, handling, and shipping to ensure optimal test results. Most tests require special handling or rapid processing to maintain sample integrity.

  • Connect with an aHUS expert

  • Treatments approved in Canada for complement-mediated TMA (aHUS)

    Generic name Trade name Manufacturer Health Canada approval for aHUS Product monograph Patient support program HTA review
    Eculizumab Soliris® Alexion Pharmaceuticals March 2013

    (first approval: Jan 2009)

    		 View OneSource™ CDA-AMC
    Ravulizumab Ultomiris® Alexion Pharmaceuticals November 2022

    (first approval: Aug 2019)

    		 View OneSource™ CDA-AMC

    TMA investigational treatments

    Generic name Manufacturer Stage of development Pivotal clinical trial(s)
    Iptacopan (anti-Factor B) Novartis Phase 3 Adult aHUS: APPELHUS (NCT04889430)
    Crovalimab (anti-C5) Roche Phase 3 Adult aHUS: COMMUTE-a (NCT04861259)
    Pediatric aHUS: COMMUTE-p (NCT04958265)
    Narsoplimab (MASP-2 inhibitor) Omeros Phase 3 Adult/adolescent aHUS (NCT03205995)
    Pediatric HSCT-TMA (NCT05855083)
    Nomacopan (anti-C5 and leukotriene B4) Akari Therapeutics Phase 3 Transplant associated TMA (NCT04784455)
    Pegcetacoplan (anti-C3) SOBI Canada Phase 2 HSCT-TMA (NCT05148299)
    Biosimilar eculizumab (ABP959) Amgen Drug submission under review by Health Canada --
  • Timeframe Within the first 6 months of treatment
    Objective To document treatment efficacy
    1
    General chemistry

    CBC, reticulocytes, LDH, bilirubin, haptoglobin, creatinine, proteinuria, peripheral blood smear, liver enzyme tests

    2
    Autoantibody cases (Anti-CFH)

    Ongoing titration monitoring

    3
    Trough levels

    CBC, CH50, and LDH (samples taken immediately before next C5i dose)

    4
    Assess genetic testing results to determine prognosis & treatment duration

    If a variant of unknown significance is identified, the patient can still be diagnosed and managed as aHUS

    5
    Repeat plasma C5b9

    To show that complement activity is normalizing

  • Timeframe Early in treatment (within the first 1–3 months)
    Objective To return to differential diagnosis

    While most patients respond well to complement inhibition therapy, some may exhibit suboptimal response. Early identification and management of these patients is crucial.4-6

    Signs of suboptimal response include:

    • Persistent thrombocytopenia beyond 7 days of therapy
    • Ongoing hemolysis (elevated LDH, low haptoglobin)
    • Worsening or non-improving renal function
    • Development of new extrarenal manifestations
    • Recurrence of TMA during treatment

    Investigate potential causes

    Suboptimal response may be due to inadequate complement blockade, presence of additional TMA triggers, coexisting conditions, or alternative diagnoses. Prompt investigation and consultation with an aHUS expert is recommended.

    First level investigations

    • Therapy compliance
    • Eculizumab / ravulizumab drug levels
    • Repeat complement markers CH50/C100 & AH50, sC5b-9
    • Reassess for other rare causes of secondary TMA (immune-mediated, glomerular nephritis, drugs, infections, malignancy)
    • SNP testing for complete non-responders
    • Stronger argument for kidney biopsy (if feasible)
    • Reassess for TTP: Repeat ADAMTS13, particularly in severely cytopenic patients or if initial result was borderline

  • For select patients who have no indication for long-term treatment, discontinuation of complement inhibition therapy may be considered. However, these patients require careful monitoring due to the risk of TMA recurrence.

    Key factors to consider before discontinuation:

    • Genetic risk profile and identified mutations
    • History of previous TMA episodes
    • Presence of ongoing TMA triggers
    • Kidney function stabilization for at least 3 months
    • Patient preference and ability to adhere to monitoring

    Close monitoring is essential

    After discontinuation of a C5 inhibitor, patients should be monitored closely with regular laboratory and clinical assessments to detect early signs of TMA recurrence. Immediate access to complement inhibition therapy should be available if recurrence is suspected.

    Post-discontinuation monitoring schedule

    Biweekly
    Monthly
    Quarterly
    Yearly
    Month 1
    Months 2-4
    Months 5-12
    Thereafter
    d1
    d15
    d28
    m2
    m3
    m4
    m6
    m9
    m12
    Yearly
    Community-based laboratory tests (standing requisition)
    CBC, reticulocyte count
    Haptoglobin, LDH
    Kidney function
    Proteinuria
    Clinical follow-ups
    Clinical assessment
    Patient self-monitoring
    Continuous

    Home monitoring includes blood pressure checks, urinalysis dipstick testing, and vigilant monitoring for TMA signs, symptoms, and triggers.

    Special assessments

    If concerned about recurrence

    After the drug washout period:

    • Repeat Core aHUS Panel
    • Kidney biopsy (if feasible)
    • Deposition C5b-9 (particularly for cases with a genetic variant of unknown significance [VUS])
    Pre-transplant workup
    • Repeat Core aHUS Panel
    • Deposition C5b-9
    • Repeat genetic screen if previous result is >2 years old

1.

McFarlane PA, et al. Can J Kidney Health Dis. 2021;8:20543581211008707.

2.

Cataland S, et al. Blood. 2019;134:1099.

3.

Kulasekararaj AG, et al. Blood Reviews. 2023;59:101041.

4.

Fakhouri F, et al. Blood. 2023;141(9):984-995.

5.

Kavanagh D, et al. Kidney International. 2024;106(6):1038-1050.

6.

Vaisbich MH, et al. Braz J Nephrol. 2025;47:e20240087.

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