What is TMA?
Thrombotic microangiopathy (TMA) is a pattern of injury, not a single disease. The small blood vessels (arterioles and capillaries) develop microthrombi, leading to:
- MICROANGIOPATHIC HAEMOLYTIC ANAEMIA — red cells fragment as they squeeze past clots (schistocytes on blood film)
- THROMBOCYTOPENIA — platelets consumed in clots
- ORGAN INJURY — especially kidneys (AKI, proteinuria, hypertension) but also brain (TTP), heart, gut
FINDING THE CAUSE matters because treatments are very different:
Primary Causes
- STEC-HUS (typical HUS): Shiga-toxin producing E. coli O157 (and others) — usually children after diarrhoea
- Atypical HUS (aHUS): complement dysregulation, usually genetic
- TTP (thrombotic thrombocytopenic purpura): severe ADAMTS13 deficiency (autoantibody or genetic)
Secondary Causes
- Malignant hypertension
- Pregnancy (pre-eclampsia/HELLP, postpartum aHUS)
- Drugs: ciclosporin, tacrolimus, gemcitabine, quinine, cocaine, ticagrelor, contrast
- Cancer
- Bone marrow transplant
- Autoimmune (lupus, scleroderma renal crisis, antiphospholipid syndrome)
- Infection (HIV, pneumococcal, COVID)
- Solid organ transplant rejection
How TMA presents
Typical Triad
- Anaemia (often sudden, brisk drop in Hb)
- Low platelets (often < 100, sometimes < 30)
- Acute kidney injury (rising creatinine, proteinuria, microhaematuria)
Other Features
- Severe high BP (often malignant)
- Jaundice (haemolysis)
- Lethargy, breathlessness
- Brain symptoms (especially TTP): confusion, seizures, focal deficit
- Heart symptoms (chest pain, arrhythmia)
- Diarrhoea ± blood (STEC-HUS) — within prior 1-2 weeks
INVESTIGATIONS (urgent):
- FBC, blood film (look for schistocytes — diagnostic clue)
- LDH (raised — haemolysis)
- Bilirubin (raised, unconjugated)
- Haptoglobin (low — haemolysis)
- Direct antiglobulin test (negative — distinguishes from autoimmune haemolysis)
- Reticulocytes (raised)
- U&E, creatinine
- Urine ACR, dipstick
- Coagulation (normal in TMA — distinguishes from DIC)
- Stool culture for STEC, PCR for Shiga toxin
- ADAMTS13 activity — < 10% = TTP
- C3, C4, factor H, factor I — for aHUS
- ANA, anti-dsDNA, complement, antiphospholipid (lupus/APLS)
- Pregnancy test
- Drug history review
- Kidney biopsy in select cases
Lab clue: schistocytes + low platelets + AKI with normal clotting = TMA until proven otherwise.
Kidney Vitality is a daily multivitamin developed by a UK Consultant Nephrologist using renal nutrition principles. It contains no added potassium, magnesium, phosphorus or iron, and no herbal blends. See the formulation.
STEC-HUS — typical HUS
Who
- Mostly children under 5
- Some adult outbreaks linked to contaminated food (UK outbreaks have been linked to leafy salads, undercooked beef, unpasteurised dairy)
Course
- 5-10 days of bloody diarrhoea (E. coli O157 or other STEC)
- Then sudden onset of pallor, oliguria, falling Hb and platelets
- AKI often requires temporary dialysis
Treatment
- Largely SUPPORTIVE
- Careful fluid management (avoid antibiotics in STEC — may worsen outcome)
- Dialysis if needed
- Transfusion as needed (cautious — fluid overload)
- Anti-D for Rh-negative pregnant patients
- Eculizumab is generally NOT used in classic STEC-HUS
Outcomes
- Most children recover within 2-4 weeks
- Long-term: ~30% have residual proteinuria, hypertension or reduced GFR — lifelong follow-up
- Mortality < 5% with modern care
Public Health
- STEC-HUS is notifiable to UKHSA
- Trace contacts and food source
- Hand hygiene messages, especially on farms, with petting zoos, and after handling raw meat
Atypical HUS — aHUS
Cause
- Complement system dysregulation
- Genetic mutations in:
- Complement Factor H (CFH) — commonest
- MCP (CD46)
- CFI, C3, CFB
- THBD (thrombomodulin)
- DGKE (children — different mechanism)
- Or autoantibodies (anti-factor H)
- Often triggered by infection, pregnancy, surgery, transplant
Diagnosis
- TMA without diarrhoea/STEC, ADAMTS13 > 10%, no obvious secondary cause
- Refer to UK National Renal Complement Therapeutics Centre (NRCTC), Newcastle
- Free genetic testing through NRCTC
TREATMENT (urgent):
- ECULIZUMAB (Soliris) — IV every 2 weeks
- OR RAVULIZUMAB (Ultomiris) — IV every 8 weeks (newer, longer-acting)
- Both NICE-approved and NHS-funded via NRCTC
- Dramatically improves outcomes from > 50% mortality to near-normal kidney survival
- Duration: often lifelong, particularly with high-risk mutations
- MENINGOCOCCAL VACCINATION required before starting (complement blockers raise meningococcal risk)
- Lifelong penicillin V prophylaxis
- Patient given alert card
Kidney Transplant
- Pre-emptive eculizumab/ravulizumab to prevent recurrence
- Best done in collaboration with NRCTC
- Liver-kidney transplant in some severe CFH cases (replaces source of mutant factor H)
Family Screening
- Genetic counselling for first-degree relatives
- Mutation-positive relatives need close monitoring during triggers (pregnancy, infection, surgery)
TTP and other TMAs
TTP (thrombotic thrombocytopenic purpura):
- ADAMTS13 < 10%
- Usually acquired (autoantibody) — sometimes congenital
- Brain involvement more prominent than kidneys (confusion, focal signs, seizures)
- Emergency: start plasma exchange same day on clinical suspicion (don't wait for ADAMTS13 result)
- PLUS steroids
- PLUS rituximab (especially if acquired)
- PLUS CAPLACIZUMAB (anti-vWF nanobody — NICE-approved) — markedly improves outcomes
- Mortality < 10% with modern care (was > 90%)
Drug-induced Tma
- Stop the drug urgently
- Calcineurin inhibitor TMA in transplant — switch, supportive care, sometimes eculizumab
- Quinine — stop, no eculizumab
- Gemcitabine — stop, eculizumab considered
Pregnancy-associated
- Pre-eclampsia / HELLP: deliver the baby
- Postpartum aHUS: same as aHUS — eculizumab
- Acute fatty liver of pregnancy: deliver
Malignant Hypertension Tma
- Treat the BP urgently (IV labetalol or hydralazine initially, then oral)
- Most TMA resolves as BP normalises
- Search for underlying cause of hypertension
Scleroderma Renal Crisis
- High-dose ACE inhibitor (captopril titrated up rapidly)
- Rheumatology input
