Suspected thrombotic microangiopathy (TMA)
Microangiopathic haemolytic anaemia (MAHA) with thrombocytopenia, with or without organ injury
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NephrologyEmergency
Thrombotic Microangiopathy (TTP, HUS, aHUS): Initial Management
Thrombotic Microangiopathy (TTP, HUS, aHUS): Initial Management: Suspected thrombotic microangiopathy (TMA) → TMA is an emergency: call haematology now ...
Pathway Overview
13 steps
Algorithm Steps
13 total
01Start 02Warning TMA is an emergency: call haematology now
Suspected TTP can be fatal within hours. Arrange transfer to a centre with plasma exchange and ICU. No plasma exchange on site: start corticosteroids; haematology may advise plasma infusion (FFP) while waiting; do not delay transfer.
- Take blood for ADAMTS13 activity and inhibitor before plasma exchange or any blood product
- Avoid platelet transfusion unless serious bleeding or a high-bleeding-risk procedure (haematology decides); do not delay plasma exchange for it
- The classic pentad (with fever, neurological and renal signs) is present in only about 40%: do not wait for it
03Action Urgent tests
Confirm MAHA and look for the cause
- FBC, reticulocytes and blood film (schistocytes)
- LDH, haptoglobin, bilirubin (indirect), direct antiglobulin test (negative in TTP)
- UEC and creatinine, LFTs, urinalysis
- PT/INR, APTT, fibrinogen, D-dimer (usually near normal in TTP; abnormal in DIC)
- Troponin and ECG; CT or MRI brain if neurological signs
- Pregnancy test (beta-hCG) in people who could be pregnant
- ADAMTS13 activity and inhibitor (anti-ADAMTS13 IgG) before plasma
- Diarrhoea: stool Shiga toxin or STEC PCR and culture
- Complement C3 and C4; HIV, hepatitis B and C serology; blood pressure
04Action PLASMIC score (adults)
Estimates the chance of severe ADAMTS13 deficiency (below 10%). Not validated in children.
- 1 point each:
- Platelets below 30 x10^9/L
- Haemolysis: reticulocytes above 2.5%, undetectable haptoglobin or indirect bilirubin above 34 micromol/L (2 mg/dL)
- No active cancer in the past year
- No solid-organ or stem cell transplant
- MCV below 90 fL
- INR below 1.5
- Creatinine below 177 micromol/L (2.0 mg/dL)
- Score 0-4: low (0-4% chance); 5: intermediate (5-24%); 6-7: high (62-82%)
05Decision Most likely cause?
Use PLASMIC score, history and first results. In adults, treat as TTP until ADAMTS13 excludes it if PLASMIC is 5-7 or suspicion is high. PLASMIC 0-4 and no clear cause: urgent ADAMTS13 and haematology advice on plasma exchange while waiting.
- TTP likely
06Action Suspected TTP: PLASMIC 5-7 or high clinical suspicion
Start treatment now. Do not wait for the ADAMTS13 result.
- Immune (acquired) TTP: autoantibody against ADAMTS13; more than 95% of TTP with ADAMTS13 below 10%
- Congenital TTP: inherited ADAMTS13 deficiency; rare; may first present in childhood or pregnancy
- ADAMTS13 below 10% confirms TTP; 10-20% is equivocal; above 20% makes TTP unlikely
- Pregnancy or postpartum: TTP, aHUS and HELLP overlap; joint haematology and obstetric care; do not delay plasma exchange
07Warning Suspected TTP: start plasma exchange now
Daily plasma exchange with corticosteroids. Avoid platelet transfusion unless serious bleeding.
- Plasma exchange as soon as possible: 1-1.5 plasma volumes (40-60 mL/kg) daily until platelet count and LDH are normal
- Corticosteroids with plasma exchange (adult): e.g. methylprednisolone 125 mg IV 2-4 times daily; haematology sets the oral taper
- Congenital TTP (known or suspected): plasma infusion 10-15 mL/kg daily until symptoms resolve, or recombinant ADAMTS13; no immunosuppression or caplacizumab
08Action Immune TTP: add-on treatment (haematology)
Caplacizumab and rituximab are added by or with a TTP-experienced haematologist.
- Caplacizumab (adult, or age 12 or more and 40 kg or more): only if suspicion is high and the ADAMTS13 result is expected within 72 h; hold if active bleeding. Australia: not on the ARTG (Special Access Scheme)
- Caplacizumab dose (EU label): 10 mg IV before the first plasma exchange, then 10 mg subcut daily after each exchange and for 30 days after the last exchange (US label: 11 mg)
- Caplacizumab: careful review with anticoagulants, antiplatelets or thrombolysis; withhold 7 days before elective procedures; no data in pregnancy
- Rituximab 375 mg/m2 IV weekly for 4 doses (adult), first event or relapse, as early as possible once TTP is likely; screen for hepatitis B first
- ADAMTS13 above 20%: stop caplacizumab and reassess for aHUS or secondary TMA
- VTE prophylaxis: mechanical while platelets below 50 x10^9/L; consider prophylactic LMWH once above 50 x10^9/L
09Action Monitoring
Track response daily
- Daily: platelet count, LDH, haemoglobin, creatinine; neurological and cardiac status
- Response: platelet count and LDH normal
- TTP: platelets not rising after 3-4 days of treatment: escalate with haematology (higher-dose steroids, rituximab or caplacizumab if not given)
- aHUS: nephrology plans C5 inhibitor duration using complement genetics
10Outcome Follow-up
TTP can relapse: check ADAMTS13 monthly for 3 months, then every 3 months for the first year, then every 6-12 months.
- TTP in remission with ADAMTS13 below 10%: haematology may give pre-emptive rituximab
- Long term after TTP: watch for mood, memory problems and hypertension
- After HUS: long-term kidney and blood pressure follow-up
- STEC-HUS
11Action STEC-HUS: bloody diarrhoea prodrome or Shiga toxin/STEC positive
Typical HUS, most common in young children. Supportive care; most recover.
- Do not give antibiotics for STEC O157, Shiga toxin 2 STEC or unknown toxin type (raises HUS risk); avoid antimotility drugs
- Careful fluid balance; dialysis for AKI, fluid overload or electrolyte problems; red cell transfusion as needed
- Adults: still send ADAMTS13 and exclude TTP
- Notify the public health unit (STEC and HUS are notifiable in Australia)
- Path rejoins step 09Shared downstream outcome
- aHUS
12Action Suspected aHUS: TTP excluded by ADAMTS13 and STEC tests negative
Complement-mediated TMA. Start a C5 inhibitor early, ideally within 24 h of suspicion (nephrology or haematology).
- Before the first dose: MenACWY and MenB vaccines; if the C5 inhibitor starts less than 2 weeks after vaccination, give antibiotic prophylaxis until 2 weeks after vaccination
- Do not start a C5 inhibitor with unresolved meningococcal infection
- Adults: continue plasma exchange until ADAMTS13 excludes TTP or the C5 inhibitor is available
- ADAMTS13 10-20% is equivocal: haematology and nephrology decide together
- Eculizumab (adult and child 40 kg or more): 900 mg IV weekly for 4 doses, then 1200 mg in week 5, then 1200 mg every 14 days (+/- 2 days)
- Eculizumab child below 40 kg: weight-band dose from the product information
- Eculizumab: give a supplemental dose with each plasma exchange or plasma infusion (see product information)
- Ravulizumab: long-acting C5 inhibitor; weight-based dose from the product information
- Fever or signs of meningococcal infection on a C5 inhibitor: emergency; give antibiotics at once
- Supportive: dialysis if needed, blood pressure control, avoid nephrotoxins
- Path rejoins step 09Shared downstream outcome
- Secondary
13Action Secondary TMA: a clear cause is present
Treat the cause. Reconsider TTP or aHUS if the TMA does not settle.
- Pregnancy or postpartum: HELLP or pre-eclampsia needs urgent obstetric care; TTP and aHUS also occur in pregnancy, so send ADAMTS13
- Drugs: stop the likely drug (e.g. quinine, gemcitabine, calcineurin inhibitors, clopidogrel)
- Malignant hypertension: controlled blood pressure lowering
- DIC (abnormal coagulation), sepsis, cancer, transplant, HIV or autoimmune disease: treat the cause
- Path rejoins step 09Shared downstream outcome
Guideline Source
2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura (with 2020 ISTH TTP diagnosis and treatment guidelines)
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- aHUS, STEC-HUS and secondary TMA content comes from other sources (aHUS expert recommendations 2023, eculizumab product information, IDSA 2017); ISTH covers TTP only
- Caplacizumab is not on the ARTG: access in Australia is through the TGA Special Access Scheme
- ADAMTS13 results can take days; treatment often starts before the diagnosis is certain
- PLASMIC score is validated in adults only
Applicable Regions
AUUSEU
AU: Caplacizumab is not on the ARTG (search 28 Sep 2026); access through the TGA Special Access Scheme. Eculizumab, ravulizumab and recombinant ADAMTS13 (Adzynma) are on the ARTG. Labs report creatinine and bilirubin in micromol/L. STEC and HUS are notifiable.
EU: Caplacizumab label dose 10 mg.
US: Caplacizumab label dose 11 mg.
Version 2Next review: 2027-09-30
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Frequently Asked Questions
What is the Thrombotic Microangiopathy (TTP, HUS, aHUS): Initial Management?
The Thrombotic Microangiopathy (TTP, HUS, aHUS): Initial Management is a emergency clinical algorithm for Nephrology. It provides a structured decision tree to guide clinical decision-making, based on 2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura (with 2020 ISTH TTP diagnosis and treatment guidelines).
What guideline is the Thrombotic Microangiopathy (TTP, HUS, aHUS): Initial Management based on?
This algorithm is based on 2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura (with 2020 ISTH TTP diagnosis and treatment guidelines) (DOI: 10.1016/j.jtha.2025.06.002).
What are the limitations of the Thrombotic Microangiopathy (TTP, HUS, aHUS): Initial Management?
Known limitations include: aHUS, STEC-HUS and secondary TMA content comes from other sources (aHUS expert recommendations 2023, eculizumab product information, IDSA 2017); ISTH covers TTP only; Caplacizumab is not on the ARTG: access in Australia is through the TGA Special Access Scheme; ADAMTS13 results can take days; treatment often starts before the diagnosis is certain; PLASMIC score is validated in adults only. Individual patient factors may require deviation from these recommendations.
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