Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 21 peer-reviewed journal articles Updated
Hematology

Biology & Diagnosis: Differentiating aHUS from TTP and STEC-HUS

At a Glance

Atypical hemolytic uremic syndrome (aHUS) is a diagnosis of exclusion. Doctors must run blood and stool tests to rule out similar conditions like TTP (using the ADAMTS13 test) and STEC-HUS (using a Shiga toxin test) before confirming aHUS and starting targeted complement inhibitor therapy.

When a person presents with the symptoms of Thrombotic Microangiopathy (TMA)—low platelets, shredded red blood cells, and organ damage—it is a medical emergency. However, doctors cannot always tell immediately what is causing the TMA [1][2]. Because there is no single “positive” test for atypical Hemolytic Uremic Syndrome (aHUS), it is considered a diagnosis of exclusion [3]. This means your medical team must systematically rule out other conditions before they can confidently diagnose aHUS and begin the correct long-term treatment [4][1].

The Diagnostic Pathway

To confirm aHUS, doctors must first prove that the patient does not have other common types of TMA. They must rule out Thrombotic Thrombocytopenic Purpura (TTP), Shiga toxin-producing E. coli HUS (STEC-HUS), and Secondary TMAs [5][3].

1. Ruling out TTP: The ADAMTS13 Test

TTP is a life-threatening condition caused by a deficiency in a specific enzyme called ADAMTS13 [6]. This enzyme acts like a pair of “molecular scissors” that clips large proteins in your blood to prevent them from clotting too easily [7].

  • The 10% Cutoff: This is the most critical number in your diagnostic workup. If the ADAMTS13 activity level is less than 10%, the patient has TTP [7][8].
  • The Outcome: If the activity level is greater than 10%, TTP is ruled out, and the doctor’s focus shifts toward aHUS [8][9]. This blood test must be drawn before the patient receives a plasma exchange, as donor blood can skew the results [10].

2. Ruling out STEC-HUS: The Shiga Toxin Test

STEC-HUS (often called “typical” HUS) is usually caused by eating contaminated food. The E. coli bacteria release a toxin—Shiga toxin—that damages the blood vessels [11][12].

  • The Test: Doctors use a stool sample or a rectal swab to perform a PCR test (which looks for the toxin’s DNA) or a culture to look for the bacteria [12][13].
  • The Outcome: If the Shiga toxin test is negative and there was no history of bloody diarrhea, STEC-HUS is unlikely, leaving aHUS as the primary suspect [3][14].

3. Ruling out Secondary TMAs

Doctors will also run tests and ask you extensive questions about your medical history to rule out Secondary TMAs. These are conditions where the tiny blood clots are a side effect of another major issue in the body. If your doctor is asking you about medications you take, running tests for autoimmune diseases like Lupus, or checking your blood pressure constantly, this is what they are doing [1]. Secondary causes can include:

  • Malignant (dangerously high) hypertension.
  • Autoimmune diseases (like Lupus or Scleroderma).
  • Certain medications (like specific chemotherapies or immunosuppressants).
  • Severe systemic infections (like Streptococcus pneumoniae).

Why Speed Matters

Differentiating between these conditions is vital because the treatments are very different [15].

  • TTP is primarily treated with plasma exchange (filtering the blood) and immune-suppressing drugs [16].
  • aHUS is best treated with complement inhibitors (like eculizumab or ravulizumab), which block the specific part of the immune system that is overactive [2][17].
  • STEC-HUS and Secondary TMAs are largely managed with supportive care and treating the underlying root cause (like lowering blood pressure or stopping an offending medication) [18][1].

The Role of Genetic Testing

While doctors rule out other diseases, they will also send blood for genetic testing. They are looking for mutations in “complement proteins” (like Factor H or Factor I) [19][20]. However, genetic tests can take weeks to return, and roughly 30–50% of patients with confirmed aHUS do not have a known genetic mutation [21]. Therefore, doctors must often make the diagnosis and start life-saving treatment based on the exclusion of TTP and STEC-HUS alone [1][2].

Condition Primary Cause Key Diagnostic Test Critical Result
TTP Enzyme deficiency (ADAMTS13) ADAMTS13 Activity < 10%
STEC-HUS Bacterial toxin (Shiga toxin) Stool PCR / Culture Positive for Shiga toxin
Secondary TMA Meds, autoimmune, severe HTN Patient history, various labs Positive for underlying condition
aHUS Complement system “glitch” Diagnosis of Exclusion All of the above ruled out

Common questions in this guide

Why is aHUS called a diagnosis of exclusion?
There is no single test that definitively proves a patient has aHUS. Instead, doctors must systematically test for and rule out other similar conditions that cause blood clots, like TTP and STEC-HUS, before confirming aHUS and starting treatment.
What is the ADAMTS13 test used for?
The ADAMTS13 test checks the activity level of a specific enzyme in your blood to rule out TTP. If the activity level is greater than 10%, TTP is ruled out and doctors will strongly suspect aHUS instead.
How do doctors test for STEC-HUS?
Doctors use a stool sample or rectal swab to run a PCR test or culture. This looks for Shiga toxin or the E. coli bacteria that usually causes typical HUS, often following a severe gastrointestinal infection.
Why does getting a fast diagnosis matter if I have TMA?
Different causes of thrombotic microangiopathy require completely different treatments. TTP requires plasma exchange, while aHUS is treated with complement inhibitors, so confirming the exact diagnosis quickly is critical for starting the correct therapy.
Will genetic testing confirm my aHUS diagnosis?
While doctors will order genetic testing to look for mutations in complement proteins, the results can take weeks. Additionally, up to half of confirmed aHUS patients have no known genetic mutation, so doctors do not wait for these results to start life-saving treatment.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What was my (or my child's) ADAMTS13 activity level? Was it above or below the 10% cutoff?
  2. 2.Did the stool test include a PCR for Shiga toxin, and how soon after the symptoms started was it collected?
  3. 3.Since aHUS is a diagnosis of exclusion, what other 'secondary' causes (like medications, autoimmune diseases, or underlying infections) have been ruled out?
  4. 4.Is the medical team waiting for these test results before starting a complement inhibitor like eculizumab or ravulizumab?
  5. 5.If we are doing plasma exchange right now, is that a 'bridge' treatment until we get the results back?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (21)
  1. 1

    [Atypical hemolytic uremic syndrome: differential diagnosis and therapy - A clinical practice guideline for diagnosis and therapy].

    Gäckler A, Brinkkötter PT

    Deutsche medizinische Wochenschrift (1946) 2025; (150(4)):167-172 doi:10.1055/a-2382-6433.

    PMID: 39879972
  2. 2

    [Ultra-early administration of eculizumab in a child with atypical hemolytic uremic syndrome: a case report].

    Guo DD, Xiao YX, Wang WR, et al.

    Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 2025; (27(11)):1408-1413 doi:10.7499/j.issn.1008-8830.2503084.

    PMID: 41250542
  3. 3

    Constipation and hemolytic uremic syndrome.

    Crawford B, Strebeck P, Saccente S

    Pediatric nephrology (Berlin, Germany) 2024; (39(2)):603-607 doi:10.1007/s00467-023-06093-8.

    PMID: 37474629
  4. 4

    Epidemiology of Atypical Hemolytic Uremic Syndrome: A Systematic Literature Review.

    Yan K, Desai K, Gullapalli L, et al.

    Clinical epidemiology 2020; (12()):295-305 doi:10.2147/CLEP.S245642.

    PMID: 32210633
  5. 5

    Coronavirus disease 2019-associated thrombotic microangiopathy treated with plasma exchange and antihypertensive therapy in a patient with HIV: A case report with literature review.

    Masuda E, Fukushima K, Hebisawa Y, et al.

    Medicine 2023; (102(41)):e35469 doi:10.1097/MD.0000000000035469.

    PMID: 37832064
  6. 6

    Comparison of clinical characteristics of first-episode thrombotic thrombocytopenic purpura and TTP-like syndrome: a retrospective cohort study in a level I hematology center in China.

    Dong G, Shi FE, Yu J, Zhu J

    Annals of hematology 2023; (102(1)):55-62 doi:10.1007/s00277-022-05030-3.

    PMID: 36385651
  7. 7

    Effect of ADAMTS13 activity turnaround time on plasma utilization for suspected thrombotic thrombocytopenic purpura.

    Connell NT, Cheves T, Sweeney JD

    Transfusion 2016; (56(2)):354-9 doi:10.1111/trf.13359.

    PMID: 26456149
  8. 8

    Combined study of ADAMTS13 and complement genes in the diagnosis of thrombotic microangiopathies using next-generation sequencing.

    Fidalgo T, Martinho P, Pinto CS, et al.

    Research and practice in thrombosis and haemostasis 2017; (1(1)):69-80 doi:10.1002/rth2.12016.

    PMID: 30046676
  9. 9

    Diagnosis and follow-up of thrombotic thrombocytopenic purpura with an automated chemiluminescent ADAMTS13 activity immunoassay.

    Beranger N, Benghezal S, Joly BS, et al.

    Research and practice in thrombosis and haemostasis 2021; (5(1)):81-93 doi:10.1002/rth2.12461.

    PMID: 33537532
  10. 10

    Microangiopathic Anemia.

    Bommer M, Bloehdorn J

    Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 2025; (52(4)):259-270 doi:10.1159/000544724.

    PMID: 40809448
  11. 11

    Novel Complement Factor B Gene Mutation Identified in a Kidney Transplant Recipient with a Shiga Toxin-Triggered Episode of Thrombotic Microangiopathy.

    Korzycka J, Pawłowicz-Szlarska E, Masajtis-Zagajewska A, Nowicki M

    The American journal of case reports 2022; (23()):e936565 doi:10.12659/AJCR.936565.

    PMID: 36306276
  12. 12

    Serology as an early diagnostic tool in pediatric patients with Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome: a post hoc analysis of a phase 2 clinical trial.

    Landivar SM, Melli LJ, Pichel M, et al.

    Journal of clinical microbiology 2026; (64(4)):e0141525 doi:10.1128/jcm.01415-25.

    PMID: 41757982
  13. 13

    Rapid culture-based identification of Shiga toxin-producing Escherichia coli and Shigella spp./Enteroinvasive E. coli using the eazyplex® EHEC complete assay.

    Penzel A, Schützler K, Dröge J, et al.

    European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2020; (39(1)):151-158 doi:10.1007/s10096-019-03704-x.

    PMID: 31529306
  14. 14

    Unusual severe case of hemolytic uremic syndrome due to Shiga toxin 2d-producing E. coli O80:H2.

    Wijnsma KL, Schijvens AM, Rossen JWA, et al.

    Pediatric nephrology (Berlin, Germany) 2017; (32(7)):1263-1268 doi:10.1007/s00467-017-3642-3.

    PMID: 28343354
  15. 15

    Prognostic utility of ADAMTS13 activity for the atypical hemolytic uremic syndrome (aHUS) and comparison of complement serology between aHUS and thrombotic thrombocytopenic purpura.

    Oh J, Oh D, Lee SJ, et al.

    Blood research 2019; (54(3)):218-228 doi:10.5045/br.2019.54.3.218.

    PMID: 31730685
  16. 16

    Immune Thrombotic Thrombocytopenic Purpura: A Review.

    Pishko AM, Li A, Cuker A

    JAMA 2025; (334(6)):517-529 doi:10.1001/jama.2025.3807.

    PMID: 40388146
  17. 17

    A Case Report of Atypical Hemolytic Uremic Syndrome Presenting With Disseminated Intravascular Coagulation.

    Brink HM, Wallworth TM, Penney SW, et al.

    Cureus 2025; (17(7)):e87437 doi:10.7759/cureus.87437.

    PMID: 40772137
  18. 18

    The role of the complement system in Shiga toxin-associated hemolytic uremic syndrome.

    Bocanegra V, Luna M, Costantino VV, et al.

    Pediatric nephrology (Berlin, Germany) 2025; (40(5)):1711-1722 doi:10.1007/s00467-024-06629-6.

    PMID: 39792253
  19. 19

    Severe hypertension and (renal) thrombotic microangiopathy: solving the puzzle.

    Wehrmann F, von Bergwelt-Baildon A, Schönermarck U

    Journal of nephrology 2023; (36(8)):2175-2177 doi:10.1007/s40620-023-01659-z.

    PMID: 37256539
  20. 20

    Diagnostic Utility of Complement Serology for Atypical Hemolytic Uremic Syndrome.

    Sridharan M, Go RS, Abraham RS, et al.

    Mayo Clinic proceedings 2018; (93(10)):1351-1362 doi:10.1016/j.mayocp.2018.07.008.

    PMID: 30286829
  21. 21

    Complement Activation and Thrombotic Microangiopathies.

    Palomo M, Blasco M, Molina P, et al.

    Clinical journal of the American Society of Nephrology : CJASN 2019; (14(12)):1719-1732 doi:10.2215/CJN.05830519.

    PMID: 31694864

This page is for educational purposes only and does not replace professional medical advice. Always consult your hematologist or healthcare team regarding your specific diagnosis and lab results.

Get notified when new evidence is published on Atypical hemolytic uremic syndrome.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.